PuSH - Publication Server of Helmholtz Zentrum München: CYP2A6 activity and cigarette consumption interact in smoking-related lung cancer susceptibility.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

EVA: Electronic Publishing

New EVA Application

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Du, M.* ; Xin, J.* ; Zheng, R.* ; Yuan, Q.* ; Wang, Z.* ; Liu, H.* ; Cai, G.* ; Albanes, D.* ; Lam, S.* ; Tardón, A.* ; Chen, C.* ; Bojesen, S.E.* ; Landi, M.T.* ; Johansson, M.* ; Risch, A.* ; Bickeböller, H.* ; Wichmann, H.-E. ; Rennert, G.* ; Arnold, S.* ; Brennan, P.* ; Field, J.K.* ; Shete, S.S.* ; Le Marchand, L.* ; Liu, G.* ; Andrew, A.S.* ; Kiemeney, L.A.* ; Zienolddiny, S.* ; Grankvist, K.* ; Caporaso, N.E.* ; Cox, A.* ; Hong, Y.C.* ; Yuan, J.M.* ; Schabath, M.B.* ; Aldrich, M.C.* ; Wang, M.* ; Shen, H.* ; Chen, F.* ; Zhang, Z.* ; Hung, R.J.* ; Amos, C.I.* ; Wei, Q.* ; Lazarus, P.* ; Christiani, D.C.*

CYP2A6 activity and cigarette consumption interact in smoking-related lung cancer susceptibility.

Cancer Res. 84, 616-625 (2024)

Postprint

DOI

	Open Access Green

Abstract
Metrics
Extra information

Cigarette smoke, containing both nicotine and carcinogens, causes lung cancer. However, not all smokers develop lung cancer, highlighting the importance of the interaction between host susceptibility and environmental exposure in tumorigenesis. Here, we aimed to delineate the interaction between metabolizing ability of tobacco carcinogens and smoking intensity in mediating genetic susceptibility to smoking-related lung tumorigenesis. Single-variant and gene-based associations of 43 tobacco carcinogen-metabolizing genes with lung cancer were analyzed using summary statistics and individual-level genetic data, followed by causal inference of Mendelian randomization, mediation analysis, and structural equation modeling. Cigarette smoke-exposed cell models were used to detect gene expression patterns in relation to specific alleles. Data from the International Lung Cancer Consortium (29,266 cases and 56,450 controls) and UK Biobank (2,155 cases and 376,329 controls) indicated that the genetic variant rs56113850 C>T located in intron 4 of CYP2A6 was significantly associated with decreased lung cancer risk among smokers (OR = 0.88, 95% confidence interval = 0.85-0.91, P = 2.18 × 10-16), which might interact (Pinteraction = 0.028) with and partially be mediated (ORindirect = 0.987) by smoking status. Smoking intensity accounted for 82.3% of the effect of CYP2A6 activity on lung cancer risk but entirely mediated the genetic effect of rs56113850. Mechanistically, the rs56113850 T allele rescued the downregulation of CYP2A6 caused by cigarette smoke exposure, potentially through preferential recruitment of transcription factor helicase-like transcription factor. Together, this study provides additional insights into the interplay between host susceptibility and carcinogen exposure in smoking-related lung tumorigenesis. SIGNIFICANCE: The causal pathway connecting CYP2A6 genetic variability and activity, cigarette consumption, and lung cancer susceptibility in smokers highlights the need for behavior modification interventions based on host susceptibility for cancer prevention.

Impact Factor

Scopus SNIP

Altmetric

12.500

0.000