Journal Article

DKFZ-2021-00533

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Causal effects of lifetime smoking on breast and colorectal cancer risk: Mendelian randomization study.

Dimou, N. ; Yarmolinsky, J. ; Bouras, E. ; Tsilidis, K. K. ; Martin, R. M. ; Lewis, S. J. ; Gram, I. T. ; Bakker, M. F. ; Brenner, H.DKFZ* ; Figueiredo, J. C. ; Turzanski-Fortner, R.DKFZ* ; Gruber, S. B. ; Van Guelpen, B. ; Hsu, L. ; Kaaks, R.DKFZ* ; Kweon, S.-S. ; Lin, Y. ; Lindor, N. M. ; Newcomb, P. A. ; Sanchez-Perez, M.-J. ; Severi, G. ; Tindle, H. A. ; Tumino, R. ; Weiderpass, E. ; Gunter, M. J. ; Murphy, N.

2021
AACR Philadelphia, Pa.

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Please use a persistent id in citations: doi:10.1158/1055-9965.EPI-20-1218

Abstract: Observational evidence has shown that smoking is a risk factor for breast and colorectal cancer. We used Mendelian randomization (MR) to examine causal associations between smoking and risks of breast and colorectal cancer.Genome-wide association study summary data were used to identify genetic variants associated with lifetime amount of smoking (n=126 variants) and ever having smoked regularly (n=112 variants). Using two-sample MR, we examined these variants in relation to incident breast (122,977 cases/105,974 controls) and colorectal cancer (52,775 cases/45,940 controls).In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [odds ratio [OR] per 1-standard deviation (SD) increment: 1.13 (95% confidence interval [CI]: 1.00-1.26); P: 0.04]; although heterogeneity was observed. Similar associations were found for estrogen receptor-positive and estrogen receptor-negative tumors. Higher lifetime amount of smoking was positively associated with colorectal cancer [OR per 1-SD increment: 1.21 (95% CI: 1.04-1.40); P: 0.01], colon cancer [OR: 1.31 (95% CI: 1.11-1.55); P: <0.01], and rectal cancer [OR: 1.36 (95% CI: 1.07-1.73); P: 0.01]. Ever having smoked regularly was not associated with risks of breast [OR: 1.01 (95% CI: 0.90-1.14); P: 0.85] or colorectal cancer [OR: 0.97 (95% CI: 0.86-1.10); P: 0.68].These findings are consistent with prior observational evidence and support a causal role of higher lifetime smoking amount in the development of breast and colorectal cancer.The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.

Note: 30(5):953-964

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)
4. C020 Epidemiologie von Krebs (C020)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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