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Causal effects of lifetime smoking on breast and colorectal cancer risk: mendelian randomization study

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...

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Main Authors: Dimou, Niki (Author) , Yarmolinsky, James (Author) , Bouras, Emmanouil (Author) , Tsilidis, Konstantinos K. (Author) , Martin, Richard M. (Author) , Lewis, Sarah J. (Author) , Gram, Inger T. (Author) , Bakker, Marije F. (Author) , Brenner, Hermann (Author) , Figueiredo, Jane C. (Author) , Turzanski Fortner, Renée (Author) , Gruber, Stephen B. (Author) , Guelpen, Bethany van (Author) , Hsu, Li (Author) , Kaaks, Rudolf (Author) , Kweon, Sun-Seog (Author) , Lin, Yi (Author) , Lindor, Noralane M. (Author) , Newcomb, Polly A. (Author) , Sánchez, Maria-Jose (Author) , Severi, Gianluca (Author) , Tindle, Hilary A. (Author) , Tumino, Rosario (Author) , Weiderpass, Elisabete (Author) , Gunter, Marc J. (Author) , Murphy, Neil (Author)
Format: Article (Journal)
Language:English
Published: March 2, 2021
In: Cancer epidemiology, biomarkers & prevention
Year: 2021, Volume: 30, Issue: 5, Pages: 953-964
ISSN:1538-7755
DOI:10.1158/1055-9965.EPI-20-1218
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1158/1055-9965.EPI-20-1218
Verlag, lizenzpflichtig, Volltext: https://cebp.aacrjournals.org/content/30/5/953
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Author Notes: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, and Neil Murphy

MARC

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245 1 0 |a Causal effects of lifetime smoking on breast and colorectal cancer risk  |b mendelian randomization study  |c 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, and Neil Murphy 
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520 |a 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. 
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