Causal Effects of Lifetime Smoking on Breast and Colorectal Cancer Risk: Mendelian Randomization Study.

Abstract

BACKGROUND:

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.

METHODS:

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).

RESULTS:

In inverse-variance weighted models, a genetic predisposition to higher lifetime amount of smoking was positively associated with breast cancer risk [OR per 1-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).

CONCLUSIONS:

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.

IMPACT:

The results from this comprehensive MR analysis indicate that lifetime smoking is a causal risk factor for these common malignancies.

• Authors: Niki Dimou, James Yarmolinsky, Emmanouil Bouras, Konstantinos K Tsilidis, Richard M Martin, Sarah J Lewis, Inger T Gram, Marije F Bakker, Hermann Brenner, Jane C Figueiredo, Renée T Fortner, Stephen B Gruber, Bethany van Guelpen, Li Hsu, Rudolf Kaaks, Sun-Seog Kweon, Yi Lin, Noralane M Lindor, Polly A Newcomb, Maria-Jose Sánchez, Gianluca Severi, Hilary A Tindle, Rosario Tumino, Elisabete Weiderpass, Marc J Gunter, Neil Murphy
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 30 Issue 5 Pg. 953-964 (05 2021) ISSN: 1538-7755 [Electronic] United States
• PMID: 33653810 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: ©2021 American Association for Cancer Research.

Topics

• Breast Neoplasms (epidemiology)
• Causality
• Colorectal Neoplasms (epidemiology)
• Female
• Genome-Wide Association Study
• Humans
• Male
• Mendelian Randomization Analysis (methods)
• Risk Factors
• Smoking (epidemiology)