TY  - JOUR
AB  - BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer cohort. METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants. CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.
AU  - Rothwell, J.A.*
AU  - Murphy, N.*
AU  - Bešević, J.*
AU  - Kliemann, N.*
AU  - Jenab, M.*
AU  - Ferrari, P.*
AU  - Achaintre, D.*
AU  - Gicquiau, A.*
AU  - Vozar, B.*
AU  - Scalbert, A.*
AU  - Huybrechts, I.*
AU  - Freisling, H.*
AU  - Prehn, C.*
AU  - Adamski, J.
AU  - Cross, A.J.*
AU  - Pala, V.M.*
AU  - Boutron-Ruault, M.C.*
AU  - Dahm, C.C.*
AU  - Overvad, K.*
AU  - Gram, I.T.*
AU  - Sandanger, T.M.*
AU  - Skeie, G.*
AU  - Jakszyn, P.*
AU  - Tsilidis, K.K.*
AU  - Aleksandrova, K.*
AU  - Schulze, M.B.*
AU  - Hughes, D.J.*
AU  - van Guelpen, B.*
AU  - Bodén, S.*
AU  - Sánchez, M.J.*
AU  - Schmidt, J.A.*
AU  - Katzke, V.*
AU  - Kühn, T.*
AU  - Colorado-Yohar, S.*
AU  - Tumino, R.*
AU  - Bueno-de-Mesquita, B.*
AU  - Vineis, P.*
AU  - Masala, G.*
AU  - Panico, S.*
AU  - Eriksen, A.K.*
AU  - Tjønneland, A.*
AU  - Aune, D.*
AU  - Weiderpass, E.*
AU  - Severi, G.*
AU  - Chajès, V.*
AU  - Gunter, M.J.*
C1  - 61231
C2  - 49768
SP  - E1061-E1082
TI  - Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort.
JO  - Clin. Gastroenterol. Hepatol.
VL  - 20
IS  - 5
PY  - 2022
SN  - 1542-3565
ER  - 

TY  - JOUR
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) may foster a tumor microenvironment that promotes cancer recurrence and progression. We examined the relationship between NAFLD and mortality among a sample of cancer survivors. METHODS: Ultrasonography was used to assess hepatic steatosis, and standardized algorithms were used to define NAFLD. Study endpoints included all-cause, cancer-specific, and cardiovascular-specific mortality. RESULTS: Among 387 cancer survivors, 17.6% had NAFLD. During a median of 17.9 years of follow up, we observed 196 deaths from all causes. In multivariable-adjusted regression models, NAFLD was associated with an increased risk of all-cause mortality [HR: 2.52, 95% CI: 1.47-4.34; P=0.001]. We observed 86 cancer-specific deaths. In multivariable-adjusted regression models, NAFLD was associated with an increased risk of cancer-specific mortality [HR: 3.21, 95% CI: 1.46-7.07; P=0.004]. We observed 46 cardiovascular-specific deaths. In multivariable-adjusted regression models, NAFLD was not associated with an increased risk of cardiovascular-specific mortality [HR: 1.04, 95% CI: 0.30-3.64, P=0.951]. CONCLUSION: NAFLD is associated with an increased risk of all-cause and cancer-specific mortality among cancer survivors. This novel observation warrants replication. Evaluating the efficacy of interventions, such as lifestyle modification through weight loss and exercise, to improve NAFLD in this population may be considered.
AU  - Stefan, N.
C1  - 53044
C2  - 44446
CY  - Po Box 211, 1000 Ae Amsterdam, Netherlands
SP  - 1043-1045
TI  - Nonalcoholic fatty liver disease and mortality.
JO  - Clin. Gastroenterol. Hepatol.
VL  - 16
IS  - 7
PB  - Elsevier Science Bv
PY  - 2018
SN  - 1542-3565
ER  - 

TY  - JOUR
AB  - BACKGROUND & AIMS: Little is known about the pathogenic mechanisms of gluten immunogenicity in patients with celiac disease. We studied temporal associations between infections and the development of celiac disease autoimmunity, and examined effects of HLA alleles, rotavirus vaccination status, and infant feeding. METHODS: We monitored 6327 children in the United States and Europe carrying HLA risk genotypes for celiac disease from 1 to 4 years of age for presence of tissue transglutaminase autoantibodies (the definition of celiac disease autoimmunity), until March 31, 2015. Parental reports of gastrointestinal and respiratory infections were collected every third month from birth. We analyzed time-varying relationships among reported infections, rotavirus vaccination status, time to first introduction of gluten, breastfeeding, and risk of celiac disease autoimmunity using proportional hazard models. RESULTS: We identified 13,881 gastrointestinal infectious episodes (GIE) and 79,816 respiratory infectious episodes. During the follow-up period, 732 of 6327 (11.6%) children developed celiac disease autoimmunity. A GIE increased the risk of celiac disease autoimmunity within the following 3 months by 33% (hazard ratio [HR], 1.33; 95% confidence interval [CI], 1.11-1.59). This risk increased 2-fold among children born in winter and introduced to gluten before age 6 months (HR, 2.08; 95% CI, 1.46-2.98), and increased 10-fold among children without HLA-DQ2 alleles and breastfed for fewer than 4 months (HR, 9.76; 95% CI, 3.87-24.8). Risk of celiac disease autoimmunity was reduced in children vaccinated against rotavirus and introduced to gluten before age 6 months (HR, 0.57; 95% CI, 0.36-0.88). CONCLUSIONS: Gastrointestinal infections increase the risk of celiac disease autoimmunity in children with genetic susceptibility to this autoimmune disorder. The risk is modified by HLA genotype, infant gluten consumption, breastfeeding, and rotavirus vaccination, indicating complex interactions among infections, genetic factors, and diet in the etiology of celiac disease in early childhood.
AU  - Kemppainen, K.M.*
AU  - Lynch, K.F.*
AU  - Liu, E.*
AU  - Lönnrot, M.*
AU  - Simell, V.*
AU  - Briese, T.*
AU  - Koletzko, S.*
AU  - Hagopian, W.*
AU  - Rewers, M.*
AU  - She, J.*
AU  - Simell, O.*
AU  - Toppari, J.*
AU  - Ziegler, A.-G.
AU  - Akolkar, B.*
AU  - Krischer, J.P.*
AU  - Lernmark, A.*
AU  - Hyoty, H.*
AU  - Triplett, E.W.*
AU  - Agardh, D.*
C1  - 51270
C2  - 42949
CY  - New York
SP  - 694-702
TI  - Factors that increase risk of celiac disease autoimmunity after a gastrointestinal infection in early life.
JO  - Clin. Gastroenterol. Hepatol.
VL  - 15
IS  - 5
PB  - Elsevier Science Inc
PY  - 2017
SN  - 1542-3565
ER  - 

TY  - JOUR
AB  - BACKGROUND & AIMS: It is not clear how intake of gluten during infancy affects subsequent risk of celiac disease. We investigated whether gluten intake before 2 years of age increases risk for celiac disease in genetically susceptible children. METHODS: We performed a case-control study of 436 pairs of children, generated from a database of 2525 children with genetic susceptibility to celiac disease in Sweden, matched for sex, birth year, and HLA genotype from September 2004 and February 2010. Children were screened annually for celiac disease using an assay for tissue transglutaminase autoantibodies (tTGA). Intestinal biopsies were collected from children who tested positive for tTGA to confirm the presence of celiac disease. Gluten intake was calculated from 3-day food records collected when the children were 9, 12, 18 and 24 months old. RESULTS: Breastfeeding duration (median 32 weeks) and age at first introduction to gluten (median 22 weeks) did not differ between cases and tTGA-negative children (controls). At the visit prior to tTGA seroconversion, cases reported a larger intake of gluten (median 4.9 g/day) than controls (median 3.9 g/day) (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.13-1.46; P=.0002). More cases consumed amounts of gluten in the upper 3rd tertile (i.e. >5.0 g/day) before they tested positive for tTGA seroconversion than controls (OR, 2.65; 95% CI, 1.70-4.13; P<.0001). This increase in risk was similar for children homozygous for DR3-DQ2 (OR, 3.19; 95% CI, 1.61-6.30; P=.001), heterozygous for DR3-DQ2 (OR, 2.24; 95% CI, 1.08≥4.62; P=.030), and for children not carrying DR3-DQ2 (OR, 2.43; 95% CI, 0.90-6.54; P=.079). CONCLUSIONS: Intake of gluten before 2 years of age increases risk of celiac disease at least 2-fold in children with genetic risk factors for this disease. This association did not differ among HLA-DR3-DQ2 haplotypes. These findings may be taken into account for future infant feeding recommendations.
AU  - Andrén Aronsson, C.*
AU  - Lee, H.S.*
AU  - Koletzko, S.*
AU  - Uusitalo, U.*
AU  - Yang, J.*
AU  - Virtanen, S.M.*
AU  - Liu, E.*
AU  - Lernmark, A.*
AU  - Norris, J.M.*
AU  - Agardh, D.*
AU  - TEDDY Study Group (Ziegler, A.-G.
AU  - Beyerlein, A.
AU  - Bonifacio, E.
AU  - Hummel, M.
AU  - Hummel, S.
AU  - Foterek, K.
AU  - Kersting, M.
AU  - Knopff, A.
AU  - Koletzko, S.
AU  - Peplow, C.
AU  - Roth, R.
AU  - Stock, J.
AU  - Strauss, E.
AU  - Warncke, K.
AU  - Winkler, C.)
C1  - 47438
C2  - 39424
CY  - New York
SP  - 403-409
TI  - Effects of gluten intake on risk of celiac disease: A case-control study on a Swedish birth cohort.
JO  - Clin. Gastroenterol. Hepatol.
VL  - 14
IS  - 3
PB  - Elsevier Science Inc
PY  - 2016
SN  - 1542-3565
ER  - 

TY  - JOUR
AU  - Stefan, N.
C1  - 48704
C2  - 41279
CY  - New York
SP  - 1345-1346
TI  - Nonalcoholic fatty liver disease and coronary artery calcification.
JO  - Clin. Gastroenterol. Hepatol.
VL  - 14
IS  - 9
PB  - Elsevier Science Inc
PY  - 2016
SN  - 1542-3565
ER  -