TY  - JOUR
AB  - Background: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer. Methods: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44, 823 ever-smokers and 20, 074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer. Results: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 ͯ 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior. Conclusions: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. Impact: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.
AU  - Li, Y.*
AU  - Xiao, X.*
AU  - Li, J.*
AU  - Han, Y.*
AU  - Cheng, C.*
AU  - Fernandes, G.F.*
AU  - Slewitzke, S.E.*
AU  - Rosenberg, S.M.*
AU  - Zhu, M.*
AU  - Byun, J.*
AU  - Bossé, Y.*
AU  - McKay, J.D.*
AU  - Albanes, D.*
AU  - Lam, S.*
AU  - Tardón, A.*
AU  - Chen, C.*
AU  - Bojesen, S.E.*
AU  - Landi, M.T.*
AU  - Johansson, M.*
AU  - Risch, A.*
AU  - Bickeböller, H.*
AU  - Wichmann, H.-E.
AU  - Christiani, D.C.*
AU  - Rennert, G.*
AU  - Arnold, S.M.*
AU  - Goodman, G.E.*
AU  - Field, J.K.*
AU  - Davies, M.P.A.*
AU  - Shete, S.*
AU  - Le Marchand, L.*
AU  - Liu, G.*
AU  - Hung, R.J.*
AU  - Andrew, A.S.*
AU  - Kiemeney, L.A.*
AU  - Sun, R.*
AU  - Zienolddiny, S.*
AU  - Grankvist, K.*
AU  - Caporaso, N.E.*
AU  - Cox, A.*
AU  - Hong, Y.C.*
AU  - Lazarus, P.*
AU  - Schabath, M.B.*
AU  - Aldrich, M.C.*
AU  - Schwartz, A.G.*
AU  - Gorlov, I.*
AU  - Purrington, K.S.*
AU  - Yang, P.*
AU  - Liu, Y.*
AU  - Bailey-Wilson, J.E.*
AU  - Pinney, S.M.*
AU  - Mandal, D.*
AU  - Willey, J.C.*
AU  - Gaba, C.*
AU  - Brennan, P.*
AU  - Xia, J.*
AU  - Shen, H.*
AU  - Amos, C.I.*
C1  - 70281
C2  - 55221
CY  - 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
SP  - 389-399
TI  - Lung cancer in ever- and never-smokers: Findings from multi-population GWAS studies.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 33
IS  - 3
PB  - Amer Assoc Cancer Research
PY  - 2024
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - BACKGROUND: Established risk factors for breast cancer include genetic disposition, reproductive factors, hormone therapy, and lifestyle-related factors such as alcohol consumption, physical inactivity, smoking, and obesity. More recently a role of environmental exposures, including air pollution, has also been suggested. The aim of this study, was to investigate the relationship between long-term air pollution exposure and breast cancer incidence. METHODS: We conducted a pooled analysis among six European cohorts (n=199,719) on the association between long-term residential levels of ambient nitrogen dioxide (NO2), fine particles (PM2.5), black carbon (BC), and ozone in the warm season (O3) and breast cancer incidence in women. The selected cohorts represented the lower range of air pollutant concentrations in Europe. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area-level. RESULTS: During 3,592,885 person-years of follow-up, we observed a total of 9,659 incident breast cancer cases. The results of the fully adjusted linear analyses showed a hazard ratio (95% confidence interval) of 1.03 (1.00, 1.06) per 10 μg/m³ NO2, 1.06 (1.01, 1.11) per 5 μg/m³ PM2.5, 1.03 (0.99, 1.06) per 0.5 10-5m-1 BC, and 0.98 (0.94, 1.01) per 10 μg/m³ O3. The effect estimates were most pronounced in the group of middle-aged women (50-54 years) and among never smokers. CONCLUSIONS: The results were in support of an association between especially PM2.5 and breast cancer. IMPACT: The findings of this study suggest a role of exposure to NO2, PM2.5 and BC in development of breast cancer.
AU  - Hvidtfeldt, U.A.*
AU  - Chen, J.*
AU  - Rodopoulou, S.*
AU  - Strak, M.*
AU  - de Hoogh, K.*
AU  - Andersen, Z.J.*
AU  - Bellander, T.*
AU  - Brandt, J.*
AU  - Fecht, D.*
AU  - Forastiere, F.*
AU  - Gulliver, J.*
AU  - Hertel, O.*
AU  - Hoffmann, B.H.*
AU  - Katsouyanni, K.*
AU  - Ketzel, M.*
AU  - Brynedal, B.*
AU  - Leander, K.*
AU  - Ljungman, P.L.S.*
AU  - Magnusson, P.K.E.*
AU  - Nagel, G.*
AU  - Pershagen, G.*
AU  - Rizzuto, D.*
AU  - Boutron-Ruault, M.C.*
AU  - Samoli, E.*
AU  - So, R.*
AU  - Stafoggia, M.*
AU  - Tjønneland, A.*
AU  - Vermeulen, R.*
AU  - Verschuren, W.M.M.*
AU  - Weinmayr, G.*
AU  - Wolf, K.
AU  - Zhang, J.*
AU  - Zitt, E.*
AU  - Brunekreef, B.*
AU  - Hoek, G.*
AU  - Raaschou-Nielsen, O.*
C1  - 66330
C2  - 53136
CY  - 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
SP  - 105-113
TI  - Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 32
IS  - 1
PB  - Amer Assoc Cancer Research
PY  - 2023
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAH) occurs widely in occupational settings. We investigated the association between occupational exposure to PAH and lung cancer risk and joint effects with smoking within the SYNERGY project. METHODS: We pooled 14 case-control studies with information on lifetime occupational and smoking histories conducted between 1985 and 2010 in Europe and Canada. Exposure to benzo[a]pyrene (BaP) was used as a proxy of PAH and estimated from a quantitative general population job exposure matrix. Multivariable unconditional logistic regression models, adjusted for smoking and exposure to other occupational lung carcinogens, estimated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 16,901 lung cancer cases and 20,965 frequency-matched controls. Adjusted OR for PAH exposure (ever) was 1.08 (CI, 1.02-1.15) in men and 1.20 (CI, 1.04-1.38) in women. When stratified by smoking status and histologic subtype, the OR for cumulative exposure >0.24 BaP µg/m3-years in men was higher in never smokers overall (1.31 (CI, 0.98-1.75)), for small cell (2.53 (CI, 1.28-4.99)) and squamous cell cancers (1.33 (CI, 0.80-2.21)). Joint effects between PAH and smoking were observed. Restricting analysis to the most recent studies showed no increased risk. CONCLUSIONS: Elevated lung cancer risk associated with PAH exposure was observed in both sexes, particularly for small cell and squamous cell cancers, after accounting for cigarette smoking and exposure to other occupational lung carcinogens. IMPACT: The lack of association between PAH and lung cancer in more recent studies merits further research under today's exposure conditions and worker protection measures.
AU  - Olsson, A.*
AU  - Guha, N.*
AU  - Bouaoun, L.*
AU  - Kromhout, H.*
AU  - Peters, S.*
AU  - Siemiatycki, J.*
AU  - Ho, V.*
AU  - Gustavsson, P.*
AU  - Boffetta, P.*
AU  - Vermeulen, R.*
AU  - Behrens, T.*
AU  - Brüning, T.*
AU  - Kendzia, B.*
AU  - Guénel, P.*
AU  - Luce, D.*
AU  - Karrasch, S.
AU  - Wichmann, H.-E.
AU  - Consonni, D.*
AU  - Landi, M.T.*
AU  - Caporaso, N.E.*
AU  - Merletti, F.*
AU  - Mirabelli, D.*
AU  - Richiardi, L.*
AU  - Jöckel, K.H.*
AU  - Ahrens, W.*
AU  - Pohlabeln, H.*
AU  - Tardón, A.*
AU  - Zaridze, D.*
AU  - Field, J.K.*
AU  - Lissowska, J.*
AU  - Swiatkowska, B.*
AU  - McLaughlin, J.R.*
AU  - Demers, P.A.*
AU  - Bencko, V.*
AU  - Foretova, L.*
AU  - Janout, V.*
AU  - Pándics, T.*
AU  - Fabianova, E.*
AU  - Mates, D.*
AU  - Forastiere, F.*
AU  - Bueno-de-Mesquita, B.*
AU  - Schüz, J.*
AU  - Straif, K.*
C1  - 64893
C2  - 52548
SP  - 1433-1441
TI  - Occupational exposure to polycyclic aromatic hydrocarbons and lung cancer risk: Results from a pooled analysis of case-control studies (SYNERGY).
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 31
IS  - 7
PY  - 2022
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Background: A growing body of evidence suggests that alterations of dietary fatty acid (FA) profiles are associated with colorectal cancer risk. However, data from large-scale epidemiologic studies using circulating FA measurements to objectively assess individual FA and FA categories are scarce. Methods: We investigate the association between red blood cell (RBC) membrane FAs and risk of colorectal cancer in a case–control study nested within a large prospective cohort. After a median follow-up of 6.4 years, 1,069 incident colorectal cancer cases were identified and matched to 1,069 controls among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). The FA composition of RBC phospholipids (in mol%) was analyzed by gas chromatography, and their association with risk of colorectal cancer was estimated by multivariable adjusted conditional logistic regression models. Results: After correction for multiple testing, subjects with higher concentrations of RBC stearic acid were at higher risk for colorectal cancer (OR ¼ 1.23; 95% CI ¼ 1.07–1.42, per 1 mol%). Conversely, colorectal cancer incidence decreased with increasing proportions of RBC n-3 PUFA, particularly eicosapentaenoic acid (0.75; 0.62–0.92, per 1 mol%). The findings for the n-6 PUFA arachidonic acid were inconsistent. Conclusions: The positive association between prediagnostic RBC stearic acid and colorectal cancer reflects putative differences in FA intake and metabolism between cancer cases and matched controls, which deserve further investigation. The inverse relationship between EPA and colorectal cancer is in line with the repeatedly reported protective effect of fish consumption on colorectal cancer risk. Impact: These findings add to the evidence on colorectal cancer prevention.
AU  - Linseisen, J.
AU  - Grundmann, N.
AU  - Zoller, D.*
AU  - Kuhn, T.*
AU  - Jansen, E.H.J.M.*
AU  - Chajes, V.*
AU  - Fedirko, V.*
AU  - Weiderpass, E.*
AU  - Dahm, C.C.*
AU  - Overvad, K.*
AU  - Tjønneland, A.*
AU  - Boutron-Ruault, M.C.*
AU  - Rothwell, J.A.*
AU  - Severi, G.*
AU  - Kaaks, R.*
AU  - Schulze, M.B.*
AU  - Aleksandrova, K.*
AU  - Sieri, S.*
AU  - Panico, S.*
AU  - Tumino, R.*
AU  - Masala, G.*
AU  - de Marco, L.*
AU  - Bueno-de-Mesquita, B.*
AU  - Vermeulen, R.*
AU  - Gram, I.T.*
AU  - Skeie, G.*
AU  - Chirlaque, M.D.*
AU  - Ardanaz, E.*
AU  - Agudo, A.*
AU  - Sánchez, M.J.*
AU  - Amiano, P.*
AU  - Wennberg, M.*
AU  - Bodén, S.*
AU  - Perez-Cornago, A.*
AU  - Aglago, E.K.*
AU  - Gunter, M.J.*
AU  - Jenab, M.*
AU  - Heath, A.K.*
AU  - Nieters, A.*
C1  - 62013
C2  - 50589
CY  - 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
SP  - 874-885
TI  - Red blood cell fatty acids and risk of colorectal cancer in the European Prospective investigation into cancer and nutrition (EPIC).
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 30
IS  - 5
PB  - Amer Assoc Cancer Research
PY  - 2021
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Background: High numbers of lymphocytes in tumor tissue, including T regulatory cells (Treg), have been associated with better colorectal cancer survival. Tregs, a subset of CD4(+) T lymphocytes, are mediators of immunosuppression in cancer, and therefore variants in genes related to Treg differentiation and function could be associated with colorectal cancer prognosis.Methods: In a prospective German cohort of 3,593 colorectal cancer patients, we assessed the association of 771 single-nucleotide polymorphisms (SNP) in 58 Treg-related genes with overall and colorectal cancer-specific survival using Cox regression models. Effect modification by microsatellite instability (MSI) status was also investigated because tumors with MSI show greater lymphocytic infiltration and have been associated with better prognosis. Replication of significant results was attempted in 2,047 colorectal cancer patients of the International Survival Analysis in Colorectal Cancer Consortium (ISACC).Results: A significant association of the TGFBR3 SNP rs7524066 with more favorable colorectal cancer-specific survival [hazard ratio (HR) per minor allele: 0.83; 95% confidence interval (CI), 0.74-0.94; P value: 0.0033] was replicated in ISACC (HR: 0.82; 95% CI, 0.68-0.98; P value: 0.03). Suggestive evidence for association was found with two IL7 SNPs, rs16906568 and rs7845577. Thirteen SNPs with differential associations with overall survival according to MSI in the discovery analysis were not confirmed.Conclusions: Common genetic variation in the Treg pathway implicating genes such as TGFBR3 and IL7 was shown to be associated with prognosis of colorectal cancer patients. Impact: The implicated genes warrant further investigation.
AU  - Neumeyer
AU  - S.
AU  - Hua, X.W.*
AU  - Seibold, P.*
AU  - Jansen, L.*
AU  - Benner, A.*
AU  - Burwinkel, B.*
AU  - Halama, N.*
AU  - Berndt, S.I.*
AU  - Phipps, A.I.*
AU  - Sakoda, L.C.*
AU  - Schoen, R.E.*
AU  - Slattery, M.L.*
AU  - Chan, A.T.*
AU  - Gala, M.*
AU  - Joshi, A.D.*
AU  - Ogino, S.*
AU  - Song, M.Y.*
AU  - Herpel, E.*
AU  - Blaker, H.*
AU  - Kloor, M.*
AU  - Scherer, D.*
AU  - Ulrich, A.*
AU  - Ulrich, C.M.*
AU  - Win, A.K.*
AU  - Figueiredo, J.C.*
AU  - Hopper, J.L.*
AU  - Macrae, F.*
AU  - Milne, R.L.*
AU  - Giles, G.G.*
AU  - Buchanan, D.D.*
AU  - Peters, U.*
AU  - Hoffmeister, M.*
AU  - Brenner, H.*
AU  - Newcomb, P.A.
AU  - Chang-Claude, J.*
C1  - 61004
C2  - 49760
CY  - 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
SP  - 2719-2728
TI  - Genetic variants in the regulatory T cell related pathway and colorectal cancer prognosis.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 29
IS  - 12
PB  - Amer Assoc Cancer Research
PY  - 2020
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Background: A substantial proportion of cancer driver genes (CDG) are also cancer predisposition genes. However, the associations between genetic variants in lung CDGs and the susceptibility to lung cancer have rarely been investigated.Methods: We selected expression-related single-nucleotide polymorphisms (eSNP) and nonsynonymous variants of lung CDGs, and tested their associations with lung cancer risk in two large-scale genome-wide association studies (20,871 cases and 15,971 controls of European descent). Conditional and joint association analysis was performed to identify independent risk variants. The associations of independent risk variants with somatic alterations in lung CDGs or recurrently altered pathways were investigated using data from The Cancer Genome Atlas (TCGA) project.Results: We identified seven independent SNPs in five lung CDGs that were consistently associated with lung cancer risk in discovery (P < 0.001) and validation (P < 0.05) stages. Among these loci, rs78062588 in TPM3 (1q21.3) was a new lung cancer susceptibility locus (OR = 0.86, P = 1.65 x 10(-6)). Subgroup analysis by histologic types further identified nine lung CDGs. Analysis of somatic alterations found that in lung adenocarcinomas, rs78062588[C] allele (TPM3 in 1q21.3) was associated with elevated somatic copy number of TPM3 (OR = 1.16, P = 0.02). In lung adenocarcinomas, rs1611182 (HLA-A in 6p22.1) was associated with truncation mutations of the transcriptional misregulation in cancer pathway (OR = 0.66, P = 1.76 x 10(-3)).Conclusions: Genetic variants can regulate functions of lung CDGs and influence lung cancer susceptibility.Impact: Our findings might help unravel biological mechanisms underlying lung cancer susceptibility.
AU  - Wang, Y.*
AU  - Gorlova, O.Y.*
AU  - Gorlov, I.P.*
AU  - Zhu, M.*
AU  - Dai, J.*
AU  - Albanes, D.*
AU  - Lam, S.*
AU  - Tardón, A.*
AU  - Chen, C.*
AU  - Goodman, G.E.*
AU  - Bojesen, S.E.*
AU  - Landi, M.T.*
AU  - Johansson, M.*
AU  - Risch, A.*
AU  - Wichmann, H.-E.
AU  - Bickeböller, H.*
AU  - Christiani, D.C.*
AU  - Rennert, G.*
AU  - Arnold, S.M.*
AU  - Brennan, P.*
AU  - Field, J.K.*
AU  - Shete, S.*
AU  - Le Marchand, L.*
AU  - Melander, O.*
AU  - Brunnström, H.*
AU  - Liu, G.*
AU  - Hung, R.J.*
AU  - Andrew, A.S.*
AU  - Kiemeney, L.A.*
AU  - Zienolddiny, S.*
AU  - Grankvist, K.*
AU  - Caporaso, N.E.*
AU  - Woll, P.J.*
AU  - Lazarus, P.*
AU  - Schabath, M.B.*
AU  - Aldrich, M.C.*
AU  - Stevens, V.L.*
AU  - Ma, H.*
AU  - Jin, G.*
AU  - Hu, Z.*
AU  - Amos, C.I.*
AU  - Shen, H.*
C1  - 59635
C2  - 48939
CY  - 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
SP  - 1423-1429
TI  - Association analysis of driver-gene related genetic variants identified novel lung cancer susceptibility loci with 20,871 lung cancer cases and 15,971 controls.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 29
IS  - 7
PB  - Amer Assoc Cancer Research
PY  - 2020
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Background: Heterocyclic amines (HCA) are potent carcinogenic substances formed in meat. Because of their mutagenic activity, they may increase the risk of colorectal adenomas, which are the precursors of colorectal cancer, one of the most prevalent cancers worldwide. The aim of this meta-analysis was to synthesize the knowledge about the intake of HCAs and its associations with CRA.Methods: We conducted a systematic search in PubMed and EMBASE. We used odds ratios (OR); or relative risks, RR) from every reported intake and compared the highest versus lowest level of dietary HCAs. In addition, we assessed a dose-response relationship.Results: Twelve studies on HCA intake and risk of CRA were included in our analysis. We observed a statistically significant association when comparing top versus bottom intake category of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine [PhIP; OR = 1.20; 95% confidence interval (CI) = 1.12-1.29], 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx; OR = 1.20; 95% CI = 1.08-1.34), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx; OR = 1.16; 95% CI = 1.05-1.27), benzo(a) pyrene (BaP; OR = 1.15; 95% CI = 1.04-1.27), and mutagenicity index (OR = 1.22; 95% CI = 1.06-1.41). Furthermore, we observed a significant dose-response effect for PhIP, MeIQx, and mutagenicity index.Conclusions: This meta-analysis suggests that there is a positive association of HCAs, BaP, mutagenicity index with risk of CRA. In addition, our dose-response analyses showed an increased risk of CRA for PhIP, MeIQx, and mutagenicity index.Impact: This study provides evidence for a positive association between the dietary intake of meat mutagens and CRA risk.
AU  - Martínez Góngora, V.*
AU  - Matthes, K.L.*
AU  - Rodríguez Castaño, P.*
AU  - Linseisen, J.
AU  - Rohrmann, S.*
C1  - 54443
C2  - 45602
CY  - 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
SP  - 99-109
TI  - Dietary heterocyclic amine intake and colorectal adenoma risk: A systematic review and meta-analysis.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 28
IS  - 1
PB  - Amer Assoc Cancer Research
PY  - 2019
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear.Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk.Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall nonsmall cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; P = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings.Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention.Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.
AU  - Zhu, Y.*
AU  - Wei, Y.*
AU  - Zhang, R.*
AU  - Dong, X.*
AU  - Shen, S.*
AU  - Zhao, Y.*
AU  - Bai, J.*
AU  - Albanes, D.*
AU  - Caporaso, N.*
AU  - Landi, M.T.*
AU  - Zhu, B.*
AU  - Chanock, S.J.*
AU  - Gu, F.*
AU  - Lam, S.*
AU  - Tsao, M.S.*
AU  - Shepherd, F.A.*
AU  - Tardón, A.*
AU  - Fernández-Somoano, A.*
AU  - Fernandez-Tardon, G.*
AU  - Chen, C.*
AU  - Barnett, M.J.*
AU  - Doherty, J.*
AU  - Bojesen, S.E.*
AU  - Johansson, M.*
AU  - Brennan, P.*
AU  - McKay, J.D.*
AU  - Carreras-Torres, R.*
AU  - Muley, T.*
AU  - Risch, A.*
AU  - Wichmann, H.-E.
AU  - Bickeboeller, H.*
AU  - Rosenberger, A.*
AU  - Rennert, G.*
AU  - Saliba, W.*
AU  - Arnold, S.M.*
AU  - Field, J.K.*
AU  - Davies, M.P.A.*
AU  - Marcus, M.W.*
AU  - Wu, X.*
AU  - Ye, Y.*
AU  - Le Marchand, L.*
AU  - Wilkens, L.R.*
AU  - Melander, O.*
AU  - Manjer, J.*
AU  - Brunnström, H.*
AU  - Hung, R.J.*
AU  - Liu, G.*
AU  - Brhane, Y.*
AU  - Kachuri, L.*
AU  - Andrew, A.S.*
AU  - Duell, E.J.*
AU  - Kiemeney, L.A.*
AU  - van der Heijden, E.H.F.M.*
AU  - Haugen, A.*
AU  - Zienolddiny, S.*
AU  - Skaug, V.*
AU  - Grankvist, K.*
AU  - Woll, P.J.*
AU  - Cox, A.*
AU  - Taylor, F.*
AU  - Teare, D.M.*
AU  - Lazarus, P.*
AU  - Schabath, M.B.*
AU  - Aldrich, M.C.*
AU  - Houlston, R.S.*
AU  - McLaughlin, J.*
AU  - Stevens, V.L.*
AU  - Shen, H.*
AU  - Hu, Z.*
AU  - Dai, J.*
AU  - Amos, C.I.*
AU  - Han, Y.*
AU  - Zhu, D.*
AU  - Goodman, G.E.*
AU  - Chen, F.*
AU  - Christiani, D.C.*
C1  - 55411
C2  - 46348
CY  - 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
SP  - 935-942
TI  - Elevated platelet count appears to be causally associated with increased risk of lung cancer: A Mendelian randomization analysis.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 28
IS  - 5
PB  - Amer Assoc Cancer Research
PY  - 2019
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - BACKGROUND: Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers and cancer related traits. METHODS: The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. RESULTS: The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. CONCLUSIONS: Results from these analyses will enable researchers to identify new susceptibility loci, perform fine mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental and lifestyle related exposures. IMPACT: Ongoing analyses will shed light on etiology and risk assessment for many types of cancer.
AU  - Amos, C.I.*
AU  - Dennis, J.*
AU  - Wang, Z.*
AU  - Byun, J.*
AU  - Schumacher, F.R.*
AU  - Gayther, S.A.*
AU  - Casey, G.*
AU  - Hunter, D.J.*
AU  - Sellers, T.A.*
AU  - Gruber, S.B.*
AU  - Dunning, A.M.*
AU  - Michailidou, K.*
AU  - Fachal, L.*
AU  - Doheny, K.F.*
AU  - Spurdle, A.B.*
AU  - Li, Y.*
AU  - Xiao, X.*
AU  - Romm, J.*
AU  - Pugh, E.N.*
AU  - Coetzee, G.A.*
AU  - Hazelett, D.J.*
AU  - Bojesen, S.E.*
AU  - Caga-Anan, C.*
AU  - Haiman, C.A.*
AU  - Kamal, A.K.*
AU  - Luccarini, C.*
AU  - Tessier, D.C.*
AU  - Vincent, D.*
AU  - Bacot, F.*
AU  - Van Den Berg, D.J.*
AU  - Nelson, S.*
AU  - Demetriades, S.*
AU  - Goldgar, D.E.*
AU  - Couch, F.J.*
AU  - Forman, J.L.*
AU  - Giles, G.G.*
AU  - Conti, D.V.*
AU  - Bickeböller, H.*
AU  - Risch, A.*
AU  - Waldenberger, M.
AU  - Brüske, I.
AU  - Hicks, B.D.*
AU  - Ling, H.*
AU  - McGuffog, L.*
AU  - Lee, A.*
AU  - Kuchenbaecker, K.B.*
AU  - Soucy, P.*
AU  - Manz, J.
AU  - Cunningham, J.M.*
AU  - Butterbach, K.*
AU  - Kote-Jarai, Z.*
AU  - Kraft, P.*
AU  - Fitzgerald, L.A.*
AU  - Lindström, S.*
AU  - Adams, M.*
AU  - McKay, J.D.*
AU  - Phelan, C.M.*
AU  - Benlloch, S.*
AU  - Kelemen, L.E.*
AU  - Brennan, P.*
AU  - Riggan, M.*
AU  - O'Mara, T.A.*
AU  - Shen, H.*
AU  - Shi, Y.Y.*
AU  - Thompson, D.J.*
AU  - Goodman, M.T.*
AU  - Nielsen, S.F.*
AU  - Berchuck, A.*
AU  - Laboissiere, S.*
AU  - Schmit, S.L.*
AU  - Shelford, T.*
AU  - Edlund, C.K.*
AU  - Taylor, J.A.*
AU  - Field, J.K.*
AU  - Park, S.K.*
AU  - Offit, K.*
AU  - Thomassen, M.*
AU  - Schmutzler, R.K.*
AU  - Ottini, L.*
AU  - Hung, R.J.*
AU  - Marchini, J.*
AU  - Amin Al Olama, A.*
AU  - Peters, U.*
AU  - Eeles, R.A.*
AU  - Seldin, M.F.*
AU  - Gillanders, E.*
AU  - Seminara, D.*
AU  - Antoniou, A.C.*
AU  - Pharoah, P.D.*
AU  - Chenevix-Trench, G.*
AU  - Chanock, S.J.*
AU  - Simard, J.*
AU  - Easton, D.F.*
C1  - 49683
C2  - 40866
CY  - Philadelphia
SP  - 126-135
TI  - The OncoArray Consortium: A network for understanding the genetic architecture of common cancers.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 26
IS  - 1
PB  - Amer Assoc Cancer Research
PY  - 2017
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. Shorter mean telomere length in leukemic cells has been associated with more aggressive disease. Germline polymorphisms in telomere maintenance genes affect telomere length and may contribute to CLL susceptibility. Methods: We collected genome-wide data from two groups of patients with CLL (N = 273) and two control populations (N = 5,725). In ancestry-adjusted case-control comparisons, we analyzed eight SNPs in genes definitively associated with inter-individual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208, and RTEL1. Results: Three of the eight LTL-associated SNPs were associated with CLL risk at P < 0.05, including those near: TERC [OR, 1.46; 95% confidence interval (CI), 1.15-1.86; P = 1.8 x 10(-3)], TERT (OR = 1.23; 95% CI, 1.02-1.48; P = 0.030), and OBFC1 (OR, 1.36; 95% CI, 1.08-1.71; P = 9.6 x 10(-3)). Using a weighted linear combination of the eight LTL-associated SNPs, we observed that CLL patients were predisposed to longer LTL than controls in both case-control sets (P = 9.4 x 10(-4) and 0.032, respectively). CLL risk increased monotonically with increasing quintiles of the weighted linear combination. Conclusions: Genetic variants in TERC, TERT, and OBFC1 are associated with both longer LTL and increased CLL risk. Because the human CST complex competes with shelterin for telomeric DNA, future work should explore the role of OBFC1 and other CST complex genes in leukemogenesis. Impact: A genetic predisposition to longer telomere length is associated with an increased risk of CLL, suggesting that the role of telomere length in CLL etiology may be distinct from its role in disease progression.
AU  - Ojha, J.*
AU  - Codd, V.*
AU  - Nelson, C.P.*
AU  - Samani, N.J.*
AU  - Smirnov, I.V.*
AU  - Madsen, N.R.*
AU  - Hansen, H.M.*
AU  - de Smith, A.J.*
AU  - Bracci, P.M.*
AU  - Wiencke, J.K.*
AU  - Wrensch, M.R.*
AU  - Wiemels, J.L.*
AU  - Walsh, K.M.*
AU  - ENGAGE Consortium Telomere Group (Albrecht, E.
AU  - Gieger, C.
AU  - Klopp, N.
AU  - Peters, A.
AU  - Wichmann, H.-E.)
C1  - 49248
C2  - 31806
CY  - Philadelphia
SP  - 1043-1049
TI  - Genetic variation associated with longer telomere length increases risk of chronic lymphocytic leukemia.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 25
IS  - 7
PB  - Amer Assoc Cancer Research
PY  - 2016
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Increasingly, targeted therapies are being developed to treat malignancies. To define targets, determine mechanisms of response and resistance, and develop biomarkers for the successful investigation of novel therapeutics, high-quality tumor biospecimens are critical. We have developed standard operating procedures (SOPs) to acquire and process serial blood and tumor biopsies from patients with diffuse large B-cell lymphoma enrolled in multicenter clinical trials. These SOPs allow for collection and processing of materials suitable for multiple downstream applications, including immunohistochemistry, cDNA microarrays, exome sequencing, and metabolomics. By standardizing these methods, we control preanalytic variables that ensure high reproducibility of results and facilitate the integration of datasets from such trials. This will facilitate translational research, better treatment selection, and more rapid and efficient development of new drugs. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology."
AU  - Nielsen, T.H.*
AU  - Diaz, Z.*
AU  - Christodoulopoulos, R.*
AU  - Charbonneau, F.*
AU  - Qureshi, S.*
AU  - Rousseau, C.*
AU  - Benlimame, N.*
AU  - Camlioglu, E.*
AU  - Constantin, A.M.*
AU  - Oros, K.K.*
AU  - Krumsiek, J.
AU  - Crump, M.*
AU  - Morin, R.D.*
AU  - Cerchietti, L.*
AU  - Johnson, N.A.*
AU  - Petrogiannis-Haliotis, T.*
AU  - Miller, W.H.*
AU  - Assouline, S.E.*
AU  - Mann, K.K.*
C1  - 42903
C2  - 35809
SP  - 2688-2693
TI  - Methods for sample acquisition and processing of serial blood and tumor biopsies for multicenter diffuse large B-cell lymphoma clinical trials.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 23
IS  - 12
PY  - 2014
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - BACKGROUND: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case-control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. METHODS: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples. RESULTS: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR = 1.37; 95% confidence interval (CI), 1.02-1.84, and OR = 1.50; 95% CI, 1.09-2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR = 1.02; 95% CI, 0.81-1.29). CONCLUSIONS: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking. IMPACT: Genetic testing for NAT2 would be inappropriate in occupational settings.
AU  - Pesch, B.*
AU  - Gawrych, K.*
AU  - Rabstein, S.*
AU  - Weiss, T.*
AU  - Casjens, S.*
AU  - Rihs, H.P.*
AU  - Ding, H.*
AU  - Angerer, J.*
AU  - Illig, T.
AU  - Klopp, N.
AU  - Bueno-de-Mesquita, H.B.*
AU  - Ros, M.M.*
AU  - Kaaks, R.*
AU  - Chang-Claude, J.*
AU  - Roswall, N.*
AU  - Tjønneland, A.*
AU  - Overvad, K.*
AU  - Clavel-Chapelon, F.*
AU  - Boutron-Ruault, M.C.*
AU  - Dossus, L.*
AU  - Boeing, H.*
AU  - Weikert, S.*
AU  - Trichopoulos, D.*
AU  - Palli, D.*
AU  - Sieri, S.*
AU  - Tumino, R.*
AU  - Panico, S.*
AU  - Quirós, J.R.*
AU  - Gonzalez, C.*
AU  - Sánchez, M.J.*
AU  - Dorronsoro, M.*
AU  - Navarro, C.*
AU  - Barricarte, A.*
AU  - Ljungberg, B.*
AU  - Johansson, M.*
AU  - Ulmert, D.*
AU  - Ehrnström, R.*
AU  - Khaw, K.T.*
AU  - Wareham, N.J.*
AU  - Key, T.J.*
AU  - Ferrari, P.*
AU  - Romieu, I.*
AU  - Riboli, E.*
AU  - Brüning, T*
AU  - Vineis, P.*
C1  - 28438
C2  - 33378
SP  - 2055-2065
TI  - N-acetyltransferase 2 phenotype, occupation, and bladder cancer risk: Results from the EPIC cohort.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 22
IS  - 11
PB  - Amer. Assoc. Cancer Res.
PY  - 2013
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - BACKGROUND: Insulin-like growth factor-1 (IGF-I) is important in normal brain development but in the adult brain, IGF-I overexpression may be a risk factor for tumor development. METHODS: We examined the association between circulating concentrations of IGF-I and IGFBP-3 in relation to risk of gliomas (74 low-grade, 206 high-grade gliomas), meningiomas (n = 174) and acoustic neuromas (n = 49) by using a case-control design nested in the European Prospective Investigation into Cancer and Nutrition. IGF-I and IGFBP-3 were measured by ELISAs.Conditional logistic regression was used to compute ORs and corresponding 95% CIs. RESULTS: The risk of low-grade gliomas was elevated with increased IGF-I (OR = 3.60, 95% CI: 1.11-11.7; top vs. bottom quartile) and decreased with elevated IGFBP-3 concentrations (OR = 0.28, 95% CI: 0.09-0.84) after mutual adjustment of these two factors; these results became nonsignificant after exclusion of the first year of follow-up. No association was observed for high-grade gliomas or meningiomas. Both high IGF-I and IGFBP-3 concentrations were associated with risk of acoustic neuromas (IGF-I: OR = 6.63, 95% CI: 2.27-19.4, top vs. bottom tertile; IGFBP-3: OR = 7.07, 95% CI: 2.32-21.6), even after excluding the first year of follow-up. CONCLUSION: High concentrations of IGF-I might be positively associated with risk of low-grade gliomas and acoustic neuromas, although we cannot exclude reverse causation, in particular for low-grade gliomas. IMPACT: Factors of the IGF axis might be involved in the etiology of some types of brain tumors.
AU  - Rohrmann, S.*
AU  - Linseisen, J.
AU  - Becker, S.*
AU  - Allen, N.*
AU  - Schlehofer, B.*
AU  - Overvad, K.*
AU  - Olsen, A.*
AU  - Tjønneland, A.*
AU  - Melin, B.S.*
AU  - Lund, E.*
AU  - Vineis, P.*
AU  - Grioni, S.*
AU  - Tumino, R.*
AU  - Palli, D.*
AU  - Mattiello, A.*
AU  - Bonet, C.*
AU  - Chirlaque, M.D.*
AU  - Sánchez, M.J.*
AU  - Rodriguez, L.*
AU  - Dorronsoro, M.*
AU  - Ardanaz, E.*
AU  - Lagiou, P.*
AU  - Trichopoulou, A.*
AU  - Trichopoulos, D.*
AU  - Dossus, L.*
AU  - Grote, V.A.*
AU  - Boeing, H.*
AU  - Aleksandrova, K.*
AU  - Bueno-de-Mesquita, H.B.*
AU  - van Duijnhoven, F.J.*
AU  - Peeters, P.H.*
AU  - Khaw, K.T.*
AU  - Wareham, N.J.*
AU  - Key, T.J.*
AU  - Rinaldi, S.*
AU  - Romieux, I.*
AU  - Gallo, V.*
AU  - Michaud, D.S.*
AU  - Riboli, E.*
AU  - Kaaks, R.*
C1  - 6903
C2  - 29409
SP  - 2174-2182
TI  - Concentrations of IGF-I and IGFBP-3 and brain tumor risk in the European Prospective Investigation into Cancer and Nutrition.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 20
IS  - 10
PB  - Amer Assoc Cancer Research
PY  - 2011
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.
AU  - Eussen, S.J.P.M.*
AU  - Vollset, S.E.*
AU  - Hustad, S.*
AU  - Midttun, O.*
AU  - Meyer, K.*
AU  - Fredriksen, A.*
AU  - Ueland, P.M.*
AU  - Jenab, M.*
AU  - Slimani, N.*
AU  - Ferrari, P.*
AU  - Agudo, A.*
AU  - Sala, N.*
AU  - Capella, G.*
AU  - Del Giudice, G.*
AU  - Palli, D.*
AU  - Boeing, H.*
AU  - Weikert, C.*
AU  - Bueno-de-Mesquita, H.B.*
AU  - Büchner, F.L.*
AU  - Carneiro, F.*
AU  - Berrino, F.*
AU  - Vineis, P.*
AU  - Tumino, R.*
AU  - Panico, S.*
AU  - Berglund, G.*
AU  - Manjer, J.*
AU  - Stenling, R.*
AU  - Hallmans, G.*
AU  - Martinez, C.*
AU  - Arrizola, L.*
AU  - Barricarte, A.*
AU  - Navarro, C.*
AU  - Rodriguez, L.*
AU  - Bingham, S.*
AU  - Linseisen, J.
AU  - Kaaks, R.*
AU  - Overvad, K.*
AU  - Tjønneland, A.*
AU  - Peeters, P.H.M.*
AU  - Numans, M.E.*
AU  - Clavel-Chapelon, F.*
AU  - Boutron-Ruault, M.C.*
AU  - Morois, S.*
AU  - Trichopoulou, A.*
AU  - Lund, E.*
AU  - Plebani, M.*
AU  - Riboli, E.*
AU  - González, C.A.*
C1  - 1647
C2  - 27286
SP  - 28-38
TI  - Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 19
IS  - 1
PB  - AACR
PY  - 2010
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - BACKGROUND: A potential dual role of folate in colorectal cancer (CRC) is currently subject to debate. We investigate the associations between plasma folate, several relevant folate-related polymorphisms, and CRC risk within the large European Prospective Investigation into Cancer and Nutrition cohort. METHODS: In this nested case-control study, 1,367 incident CRC cases were matched to 2,325 controls for study center, age, and sex. Risk ratios (RR) were estimated with conditional logistic regression and adjusted for smoking, education, physical activity, and intake of alcohol and fiber. RESULTS: Overall analyses did not reveal associations of plasma folate with CRC. The RR (95% confidence interval; Ptrend) for the fifth versus the first quintile of folate status was 0.94 (0.74-1.20; 0.44). The polymorphisms MTHFR677C-->T, MTHFR1298A-->C, MTR2756A-->G, MTRR66A-->G, and MTHFD11958G-->A were not associated with CRC risk. However, in individuals with the lowest plasma folate concentrations, the MTHFR 677TT genotype showed a statistically nonsignificant increased CRC risk [RR (95% CI; Ptrend) TT versus CC=1.39 (0.87-2.21); 0.12], whereas those with the highest folate concentrations showed a nonsignificant decreased CRC risk [RR TT versus CC=0.74 (0.39-1.37); 0.34]. The SLC19A180G-->A showed a positive association with CRC risk [RR AA versus GG 1.30 (1.06-1.59); <0.01]. CONCLUSIONS: This large European prospective multicenter study did not show an association of CRC risk with plasma folate status nor with MTHFR polymorphisms. IMPACT: Findings of the present study tend to weaken the evidence that folate plays an important role in CRC carcinogenesis. However, larger sample sizes are needed to adequately address potential gene-environment interactions.
AU  - Eussen, S.J.P.M.*
AU  - Vollset, S.E.*
AU  - Igland, J.*
AU  - Meyer, K.*
AU  - Fredriksen, A.*
AU  - Ueland, P.M.*
AU  - Jenab, M.*
AU  - Slimani, N.*
AU  - Boffetta, P.*
AU  - Overvad, K.*
AU  - Tjønneland, A.*
AU  - Olsen, A.*
AU  - Clavel-Chapelon, F.*
AU  - Boutron-Ruault, M.C.*
AU  - Morois, S.*
AU  - Weikert, C.*
AU  - Pischon, T.*
AU  - Linseisen, J.
AU  - Kaaks, R.*
AU  - Trichopoulou, A.*
AU  - Zilis, D.*
AU  - Katsoulis, M.*
AU  - Palli, D.*
AU  - Berrino, F.*
AU  - Vineis, P.*
AU  - Tumino, R.*
AU  - Panico, S.*
AU  - Peeters, P.H.M.*
AU  - Bueno-de-Mesquita, H.B.*
AU  - van Duijnhoven, F.J.*
AU  - Gram, I.T.*
AU  - Skeie, G.*
AU  - Lund, E.*
AU  - González, C.A.*
AU  - Martinez, C.*
AU  - Dorronsoro, M.*
AU  - Ardanaz, E.*
AU  - Navarro, C.*
AU  - Rodriguez, L.*
AU  - van Guelpen, B.*
AU  - Palmqvist, R.*
AU  - Manjer, J.*
AU  - Ericson, U.*
AU  - Bingham, S.*
AU  - Khaw, K.T.*
AU  - Norat, T.*
AU  - Riboli, E.*
C1  - 5903
C2  - 27415
SP  - 1328-1340
TI  - Plasma folate, related genetic variants, and colorectal cancer risk in EPIC.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 19
IS  - 5
PB  - American Assoc. for Cancer Research
PY  - 2010
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Background: B-vitamins are essential for one-carbon metabolism and have been linked to colorectal cancer. Although associations with folate have frequently been studied, studies on other plasma vitamins B2, B6, and B12 and colorectal cancer are scarce or inconclusive. Methods: We carried out a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, including 1,365 incident colorectal cancer cases and 2,319 controls matched for study center, age, and sex. We measured the sum of B2 species riboflavin and flavin mononucleotide, and the sum of B6 species pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid as indicators for vitamin B2 and B6 status, as well as vitamin B12 in plasma samples collected at baseline. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for colorectal cancer were estimated using conditional logistic regression, adjusted for smoking, education, physical activity, body mass index, alcohol consumption, and intakes of fiber and red and processed meat. Results: The relative risks comparing highest to lowest quintile were 0.71 [95% confidence interval (95% CI), 0.56-0.91; P-trend = 0.02] for vitamin B2, 0.68 (95% CI, 0.53-0.87; P-trend <0.001) for vitamin B6, and 1.02 (95% CI, 0.80-1.29; P-trend = 0.19) for vitamin B12. The associations for vitamin B6 were stronger in males who consumed >= 30 g alcohol/day. The polymorphisms were not associated with colorectal cancer. Conclusions: Higher plasma concentrations of vitamins B2 and B6 are associated with a lower colorectal cancer risk. Impact: This European population-based study is the first to indicate that vitamin B2 is inversely associated with colorectal cancer, and is in agreement with previously suggested inverse associations of vitamin B6 with colorectal cancer.
AU  - Eussen, S.J.P.M.*
AU  - Vollset, S.E.*
AU  - Hustad, S.*
AU  - Midttun, O.*
AU  - Meyer, K.*
AU  - Fredriksen, A.*
AU  - Ueland, P.M.*
AU  - Jenab, M.*
AU  - Slimani, N.*
AU  - Boffetta, P.*
AU  - Overvad, K.*
AU  - Thorlacius-Ussing, O.*
AU  - Tjonneland, A.*
AU  - Olsen, A.*
AU  - Clavel-Chapelon, F.*
AU  - Boutron-Ruault, M.C.*
AU  - Morois, S.*
AU  - Weikert, C.*
AU  - Pischon, T.*
AU  - Linseisen, J.
AU  - Kaaks, R.*
AU  - Trichopoulou, A.*
AU  - Zilis, D.*
AU  - Katsoulis, M.*
AU  - Palli, D.*
AU  - Pala, V.*
AU  - Vineis, P.*
AU  - Tumino, R.*
AU  - Panico, S.*
AU  - Peeters, P.H.M.*
AU  - Bueno-de-Mesquita, H.B.*
AU  - van Duijnhoven, F.J.*
AU  - Skeie, G.*
AU  - Muñoz, X.*
AU  - Martinez, C.*
AU  - Dorronsoro, M.*
AU  - Ardanaz, E.*
AU  - Navarro, C.*
AU  - Rodriguez, L.*
AU  - van Guelpen, B.*
AU  - Palmqvist, R.*
AU  - Manjer, J.*
AU  - Ericson, U., Bingham, S.*
AU  - Khaw, K.T.*
AU  - Norat, T.*
AU  - Riboli, E.*
C1  - 6142
C2  - 28127
CY  - Philadelphia
SP  - 2549-2561
TI  - Plasma vitamins B2, B6, and B12, and related genetic variants as predictors of colorectal cancer risk.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 19
IS  - 10
PB  - Amer. Assoc. Cancer Reseach
PY  - 2010
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - BACKGROUND: Recently, biological markers related to the immune system such as cytokines have been studied to further understand the etiology of non-Hodgkin Lymphoma (NHL). However, to date, there are no studies that have studied cytokine levels prospectively in relation to NHL risk in the general population. METHODS: Using bead-based immunoassays, plasma levels of 11 cytokines, 4 chemokines, and 1 adhesion molecules were measured in prediagnostic blood samples of 86 NHL cases and 86 matched controls (average time between blood collection and diagnosis, 4.5 y). Conditional logistic regression adjusted for body mass index and alcohol consumption was used to analyze the association between individual plasma cytokine levels and the risk of developing NHL. RESULTS: In multivariate models, excluding cases diagnosed within 2 years after inclusion, we observed a significant association for interleukin 2 (IL2; P trend = 0.004), interferon (IFN)-gamma (P trend = 0.05), and intercellular adhesion molecule (ICAM) (P trend = 0.04). Subanalyses of B-cell NHL patients showed a significant association with IL2 (P trend = 0.003), tumor necrosis factor-alpha (TNF-alpha; P trend = 0.03), and ICAM (P trend = 0.04) and a borderline association with IL5 (P trend = 0.07) and IFN-gamma (P trend = 0.08). CONCLUSIONS: The results of this study suggest, in a prospective setting, a possible association between plasma levels of IL2, ICAM, IFN-gamma, and TNF-alpha with NHL risk and provide some evidence that risk of NHL might be related to a downregulation of T helper 1 cytokines. IMPACT: Identification of subtle changes in immune response regulation quantified by plasma cytokine levels possibly provides new insights in the etiology of NHL.
AU  - Hosnijeh, F.S.*
AU  - Krop, E.J.M.*
AU  - Scoccianti, C.*
AU  - Krogh, V.*
AU  - Palli, D.*
AU  - Panico, S.*
AU  - Tumino, R.*
AU  - Sacredote, C.*
AU  - Nawroly, N.*
AU  - Portengen, L.*
AU  - Linseisen, J.
AU  - Vineis, P.*
AU  - Vermeulen, R.*
C1  - 5854
C2  - 27692
SP  - 1577-1584
TI  - Plasma cytokines and future risk of non-Hodgkin lymphoma (NHL): A case-control study nested in the Italian European Prospective Investigation into Cancer and Nutrition.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 19
IS  - 6
PB  - American Assoc. for Cancer Research
PY  - 2010
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - A protective role of glucosinolates in prostate cancer development might be mediated by the induction of biotransformation enzymes. These enzymes, enhancing the elimination of carcinogens from the body, are known to be polymorphic. Therefore, we evaluated whether a possible association between glucosinolate intake and prostate cancer risk is modified by polymorphisms in GSTT1, GSTM1, GSTA1, GSTP1, or NOQ1 genes. A case-control study including 248 prostate cancer cases and 492 matched controls was nested in the prospective European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort. At baseline, participants provided dietary and lifestyle data and blood samples, which were used for genotyping and measurement of serum glutathione S-transferase-alpha concentration. Odds ratios and 95% confidence intervals were calculated by conditional logistic regression. We found an inverse association of glucosinolate intake with prostate cancer risk (adjusted odds ratio, 0.72 per 10 mg/d increment; 95% confidence interval, 0.53-0.96). Stratification by genotype showed significantly reduced risks for subjects with wild-type of NQO1 (C609T) compared with CT or TT carriers (P(interaction) = 0.04). Those with deletions in both GSTM1 and GSTT1 genes combined had a significantly reduced risk with increasing glucosinolate intake (P(interaction) = 0.01). There was no effect modification of glucosinolate intake and cancer risk by GSTA1 (G-52A) or GSTP1 (A313G) genotype, but serum glutathione S-transferase-alpha concentrations were inversely associated with prostate cancer. This study showed that the inverse association between glucosinolate intake and prostate cancer risk was modified by NQO1 (C609T) and GSTM1 and GSTT1 deletion polymorphisms. This information will help to further elucidate the mechanism of action of potentially protective substances in vivo.
AU  - Steinbrecher, A.*
AU  - Rohrmann, S.*
AU  - Timofeeva, M.*
AU  - Risch, A.*
AU  - Jansen, E.*
AU  - Linseisen, J.
C1  - 1646
C2  - 27285
SP  - 135-143
TI  - Dietary glucosinolate intake, polymorphisms in selected biotransformation enzymes, and risk of prostate cancer.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 19
IS  - 1
PB  - AACR
PY  - 2010
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Background: Evidence for an association between selenium status and prostate cancer risk is still inconclusive. Anticarcinogenic effects of selenium are supposedly mediated through cellular protective and redox properties of selenoenzymes in vivo. We evaluated the association between serum selenium status and prostate cancer risk in a population with relative low selenium concentrations considering effect modification by genetic variants in selenoprotein genes. Materials and Methods: A case-control study of 248 incident prostate cancer cases and 492 matched controls was nested within the EPIC-Heidelberg cohort. Baseline blood samples were analyzed for serum selenium and selenoprotein P concentrations and glutathione peroxidase activity. Genotyping was carried out for SEP15 (rs5859, rs540049), SEPP1 (rs3877899, rs7579), GPX1 (rs1050450), and GPX4 (rs713041). Conditional logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Results: The OR for prostate cancer was 0.89 (95% CI, 0.79-1.01) per 10 mu g/L increase of serum selenium concentration. This association was modified by rs1050450 (C>T) in GPX1 (P-interaction = 0.03), with carriers of one or two T alleles having a significantly reduced OR of 0.87 (95% CI, 0.76-0.99). Furthermore, there was an association between rs7579 genotype in SEPP1 and prostate cancer risk (OR, 1.72; 95% CI, 0.99-2.98). Conclusions: Our results support a role of selenium and polymorphisms in selenoenzymes in prostate cancer etiology, which warrants confirmation in future studies. Impact: These findings might help to explain biological effects of selenium in prostate cancer development in order to overcome inconsistencies arising from former studies.
AU  - Steinbrecher, A.*
AU  - Méplan, C.*
AU  - Hesketh, J.*
AU  - Schomburg, L.*
AU  - Endermann, T.*
AU  - Jansen, E.*
AU  - Akesson, B.*
AU  - Rohrmann, S.*
AU  - Linseisen, J.
C1  - 4739
C2  - 28000
CY  - Philadelphia
SP  - 2958-2968
TI  - Effects of selenium status and polymorphisms in selenoprotein genes on prostate cancer risk in a prospective study of European men.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 19
IS  - 11
PB  - Amer. Assoc. Cancer Research
PY  - 2010
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - BACKGROUND: The International Lung Cancer Consortium was established in 2004. To clarify the role of DNA repair genes in lung cancer susceptibility, we conducted a pooled analysis of genetic variants in DNA repair pathways, whose associations have been investigated by at least 3 individual studies. METHODS: Data from 14 studies were pooled for 18 sequence variants in 12 DNA repair genes, including APEX1, OGG1, XRCC1, XRCC2, XRCC3, ERCC1, XPD, XPF, XPG, XPA, MGMT, and TP53. The total number of subjects included in the analysis for each variant ranged from 2,073 to 13,955 subjects. RESULTS: Four of the variants were found to be weakly associated with lung cancer risk with borderline significance: these were XRCC3 T241M [heterozygote odds ratio (OR), 0.89; 95% confidence interval (95% CI), 0.79-0.99 and homozygote OR, 0.84; 95% CI, 0.71-1.00] based on 3,467 cases and 5,021 controls from 8 studies, XPD K751Q (heterozygote OR, 0.99; 95% CI, 0.89-1.10 and homozygote OR, 1.19; 95% CI, 1.02-1.39) based on 6,463 cases and 6,603 controls from 9 studies, and TP53 R72P (heterozygote OR, 1.14; 95% CI, 1.00-1.29 and homozygote OR, 1.20; 95% CI, 1.02-1.42) based on 3,610 cases and 5,293 controls from 6 studies. OGG1 S326C homozygote was suggested to be associated with lung cancer risk in Caucasians (homozygote OR, 1.34; 95% CI, 1.01-1.79) based on 2,569 cases and 4,178 controls from 4 studies but not in Asians. The other 14 variants did not exhibit main effects on lung cancer risk. DISCUSSION: In addition to data pooling, future priorities of International Lung Cancer Consortium include coordinated genotyping and multistage validation for ongoing genome-wide association studies.
AU  - Hung, R.J.*
AU  - Christiani, D.C.*
AU  - Risch, A.*
AU  - Popanda, O.*
AU  - Haugen, A.*
AU  - Zienolddiny, S.*
AU  - Benhamou, S.*
AU  - Bouchardy, C.*
AU  - Lan, Q.*
AU  - Spitz, M.R.*
AU  - Wichmann, H.-E.
AU  - LeMarchand, L.*
AU  - Vineis, P.*
AU  - Matullo, G.*
AU  - Kiyohara, C.*
AU  - Zhang, Z.F.*
AU  - Pezeshki, B.*
AU  - Harris, C.*
AU  - Mechanic, L.*
AU  - Seow, A.*
AU  - Ng, D.P.*
AU  - Szeszenia-Dabrowska, N.*
AU  - Zaridze, D.*
AU  - Lissowska, J.*
AU  - Rudnai, P.*
AU  - Fabianova, E.*
AU  - Mates, D.*
AU  - Foretova, L.*
AU  - Janout, V.*
AU  - Bencko, V.*
AU  - Caporaso, N.*
AU  - Chen, C.*
AU  - Duell, E.J.*
AU  - Goodman, G.*
AU  - Field, J.K.*
AU  - Houlston, R.S.*
AU  - Hong, Y.C.*
AU  - Landi, M.T.*
AU  - Lazarus, P.*
AU  - Muscat, J.*
AU  - McLaughlin, J.*
AU  - Schwartz, A.G.*
AU  - Shen, H.*
AU  - Stücker, I.*
AU  - Tajima, K.*
AU  - Matsuo, K.*
AU  - Thun, M.*
AU  - Yang, P.*
AU  - Wiencke, J.*
AU  - Andrew, A.S.*
AU  - Monnier, S.*
AU  - Boffetta, P.*
AU  - Brennan, P.*
C1  - 2247
C2  - 26334
SP  - 3081-3089
TI  - International Lung Cancer Consortium: Pooled analysis of sequence variants in DNA repair and cell cycle pathways.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 17
IS  - 11
PB  - American Assoc. for Cancer Research
PY  - 2008
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Matrix metalloproteinases (MMP) play a key role in the breakdown of extracellular matrix and in inflammatory processes. MMP1 is the most highly expressed interstitial collagenase degrading fibrillar collagens. Overexpression of MMP1 has been shown in tumor tissues and has been suggested to be associated with tumor invasion and metastasis. Nine haplotype tagging and additional two intronic single nucleotide polymorphisms (SNP) of MMP1 were genotyped in a case control sample, consisting of 635 lung cancer cases with onset of disease below 51 years of age and 1,300 age- and sex-matched cancer-free controls. Two regions of linkage disequilibrium (LD) of MMP1 could be observed: a region of low LD comprising the 5' region including the promoter and a region of high LD starting from exon 1 to the end of the gene and including the 3' flanking region. Several SNPs were identified to be individually significantly associated with risk of early-onset lung cancer. The most significant effect was seen for rs1938901 (P = 0.0089), rs193008 (P = 0.0108), and rs996999 (P = 0.0459). For rs996999, significance vanished after correction for multiple testing. For each of these SNPs, the major allele was associated with an increase in risk with an odds ratio between 1.2 and 1.3 (95% confidence interval, 1.0-1.5). The haplotype analysis supported these findings, especially for subgroups with high smoking intensity. In summary, we identified MMP1 to be associated with an increased risk for lung cancer, which was modified by smoking.
AU  - Sauter, W.
AU  - Rosenberger, A.*
AU  - Beckmann, L.*
AU  - Kropp, S.*
AU  - Mittelstraß, K.
AU  - Timofeeva, M.*
AU  - Wölke, G.
AU  - Steinwachs, A.
AU  - Scheiner, D.
AU  - Meese, E.*
AU  - Sybrecht, G.*
AU  - Kronenberg, F.*
AU  - Dienemann, H*
AU  - LUCY Consortium (*)
AU  - Chang-Claude, J.*
AU  - Illig, T.
AU  - Wichmann, H.-E.
AU  - Bickeböller, H.*
AU  - Risch, A.*
C1  - 779
C2  - 25389
SP  - 1127-1135
TI  - Matrix metalloproteinase 1 (MMP1) is associated with early-onset lung cancer.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 17
IS  - 5
PB  - American Assoc. for Cancer Research
PY  - 2008
SN  - 1055-9965
ER  - 

TY  - JOUR
AU  - Rabstein, S.*
AU  - Unfried, K.*
AU  - Ranft, U.*
AU  - Illig, T.
AU  - Kolz, M.
AU  - Rihs, H.-P.*
AU  - Mambetova, C.*
AU  - Vlad, M.*
AU  - Brüning, T*
AU  - Pesch, B.*
C1  - 3025
C2  - 23850
SP  - 138-141
TI  - Variation of the N-acetyltransferase 2 gene in a Romanian and a Kyrgyz population.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 15
PY  - 2006
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Neoplastic development and growth are suspected to be influenced by availability and metabolism of folate due to effects on gene expression through DNA methylation and on genome integrity through DNA synthesis and repair (1-3). Key enzymatic regulators are methylene-tetrahydrofolate reductase (MTHFR) reducing 5,10-methylene-tetrahydrofolate to 5-methyl-tetrahydrofolate, the plasma form of folate and carbon donor for the remethylation of homocysteine to methionine (4), the methionine synthase (MTR) catalyzing methylation towards S-adenosyl-methionine (4), and thymidylate synthase (TYMS) catalyzing both the conversion of 5,10-methylene-tetrahydrofolate to dihydrofolate and of deoxyuridylate to deoxythymidylate, a rate-limiting nucleotide of DNA synthesis (5). Common variants MTHFR_677_C>T Ala222Val and MTHFR_1298_A>C Glu429Ala are associated with reduced in vitro enzyme activity (6-8), thereby increasing the availability of folate for thymidylate and purine synthesis, affect mRNA level in case of the TYMS_1494_del (TAAAGT) polymorphism (9), or are thought to affect the enzymatic activity and induce modest homocysteine reduction and DNA hypomethylation in case of the MTR_2756_A>G Asp919Gly polymorphism (10-12). Although MTHFR variants are associated with a decreased risk for colon cancer (13), conflicting data on their association with breast cancer exist (14-25). For this reason, we investigated MTHFR, MTR, and TYMS polymorphisms in a population-based breast cancer case-control study (GENICA) from Germany for their potential role in breast cancer risk.
AU  - Justenhoven, Ch.*
AU  - Vollmert, C.
AU  - Illig, T.
C1  - 4239
C2  - 23330
SP  - 3015-3018
TI  - One-Carbon Metabolism and Breast Cancer Risk: No Association of MTHFR, MTR and TYMS - Polymorphisms in the GENICA Study from Germany.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 14
PY  - 2005
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Purpose: The objective of the study was to examine the association of three exon 5 variants in the O6-alkylguanine DNA alkyltransferase (AGT) gene involved in the repair of the mutagenic DNA lesion O6-alkylguanine formed by nitrosamines, with lung cancer risk in never-smokers. Experimental Design: Exon 5 of the AGT gene was sequenced in genomic DNA from 136 cases and 133 hospital- or population-based controls for whom questionnaire information on second-hand smoke and diet was available to determine the frequencies of the Gly160Arg, Ile143Val, and Lys178Arg variant alleles. Results: No codon 160Arg variant alleles were found in the study population. The codon 143Val and 178Arg variant alleles, present at allele frequencies of 0.07, showed 100% linkage. The odds ratio (OR) of lung cancer for these variant carriers was 2.05 [95% confidence interval (CI) 1.03–4.07]. The risk varied between the different lung cancer pathologies with an increased risk for adenocarcinoma (OR 2.67, 95% CI 1.21–5.87) or small cell carcinoma (OR 4.83, 95% CI 0.91–25.7) but not for squamous cell carcinoma (OR 1.07, 95% CI 0.27–4.18). Compared with individuals carrying the mutant alleles unexposed to second-hand smoke, the OR for exposed variant carriers was 1.95 (95% CI 0.53–1.15); a similar interaction, although not significative, was observed for low consumption of cruciferous vegetables and for green vegetables and tomatoes. Conclusions: These results point toward a role of AGT polymorphisms in lung cancer susceptibility among never-smokers, in particular among subjects exposed to environmental carcinogens.
AU  - Cohet, C.*
AU  - Borel, S.*
AU  - Nyberg, F.*
AU  - Mukeria, A.*
AU  - Brüske, I.
AU  - Constantinescu, V.*
AU  - Benhamou, S.*
AU  - Brennan, P.*
AU  - Hall, J.*
AU  - Boffetta, P.*
C1  - 1057
C2  - 22017
SP  - 320-323
TI  - Exon 5 polymorphisms in the O6-alkylguanine DNA alkyltransferase gene and lung cancer risk in non-smokers exposed to second-hand smoke.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 13
PY  - 2004
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - The polygenic concept of breast cancer susceptibility calls for the identification of genetic variants that contribute to breast cancer risk. Reduced DNA repair proficiencies in women with breast cancer pointed to a possible role of DNA repair enzymes in the risk to develop the disease. The nucleotide excision repair enzyme encoded by the excision repair cross-complementing group 2 gene ERCC2 (formerly XPD) known to cause skin cancer by germ line mutations has multiple regulatory cellular functions, including nucleotide excision repair, basal transcription, cell cycle control, and apoptosis. ERCC2 polymorphisms ERCC2_6540_G>A (Asp312Asn) and ERCC2_18880_A>C (Lys751Gln) within the coding region of this evolutionarily highly conserved gene have been of functional relevance and therefore are potential candidates to confer breast cancer susceptibility. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we analyzed genotype frequencies in constitutional DNA of study participants of a German case-control study that included 688 cases of incident breast cancer and 724 population-based, age-matched controls. We identified ERCC2_6540_GG (Asp312Asp) as an at-risk genotype [odds ratio (OR), 2.06; 95% confidence interval (95% CI), 1.39-3.07]. The ERCC2_6540_GG-associated breast cancer risk was even higher in women who were also carriers of the ERCC2_18880_CC (Gln751Gln) genotype (OR, 3.69; 95% CI, 1.76-7.74). We identified ERCC2_6540_G/ERCC2_18880_C (Asp312/Gln751) as the most potent risk-conferring haplotype (OR, 3.49; 95% CI, 2.30-5.28). To our knowledge, this is the first study assigning breast cancer risk to both the ERCC2 genotype encoding Asp312Asp and the haplotype encoding Asp312/Gln751.
AU  - Justenhoven, C.*
AU  - Hamann, U.*
AU  - Pesch, B.*
AU  - Harth, V.*
AU  - Rabstein, S.*
AU  - Baisch, C.*
AU  - Vollmert, C.
AU  - Illig, T.
AU  - Ko, Y.-D.*
AU  - Brüning, T*
AU  - Brauch, H.*
C1  - 4625
C2  - 22462
SP  - 2059-2064
TI  - ERCC2 genotypes and a corresponding haplotype are linked with breast cancer risk in a German population.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 13
PY  - 2004
SN  - 1055-9965
ER  - 

TY  - JOUR
AB  - Glutathione S-transferase (GST) polymorphism may contribute to the individual variability in detoxifying lung carcinogens. This effect might be particularly relevant at low-level exposure to environmental carcinogens, such as in nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case-control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls from eight countries. Information on environmental exposures was obtained through a personal interview. The presence of GSTM1 and GSTT1 genes was determined using multiplex PCR. GSTM1-positive samples were then analyzed for *1A and* 1B polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9–2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9–6.1) than for cases with adenocarcinomas. It was also elevated in individuals with long-term exposure to indoor wood combustion (OR, 3.1; 95% CI, 0.9–9.9), in subjects who mainly lived in a rural setting (OR, 3.6; 95% CI, 1.0–13), and in cases exposed to occupational carcinogens (OR, 10.7; 96% CI, 0.4–260) but not in subjects exposed to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in smokers. It does not seem to interact with ETS exposure, although we cannot exclude that it does in association with exposure to other specific environmental carcinogens.
AU  - Malats, N.*
AU  - Camus-Radon, A.*
AU  - Nyberg, F.*
AU  - Ahrens, W.*
AU  - Constantinescu, V.*
AU  - Mukeria, A.*
AU  - Benhamou, S.*
AU  - Batura-Gabryel, H.*
AU  - Brüske, I.
AU  - Simonato, L.*
AU  - Menezes, A.*
AU  - Lea, S.*
AU  - Lang, M.*
AU  - Boffetta, P.*
C1  - 21682
C2  - 19882
SP  - 827-833
TI  - Lung Cancer Risk in Nonsmokers and GSTM1 and GSTT1 Genetic Polymorphism.
JO  - Cancer Epidemiol. Biomarkers Prev.
VL  - 9
PY  - 2000
SN  - 1055-9965
ER  -