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@article{Dimou:2021:10.1158/1055-9965.EPI-20-1218,
author = {Dimou, N and Yarmolinsky, J and Bouras, E and Tsilidis, KK and Martin, RM and Lewis, SJ and Gram, IT and Bakker, MF and Brenner, H and Figueiredo, JC and Fortner, RT and Gruber, SB and Van, Guelpen B and Hsu, L and Kaaks, R and Kweon, S-S and Lin, Y and Lindor, NM and Newcomb, PA and Sanchez-Perez, M-J and Severi, G and Tindle, HA and Tumino, R and Weiderpass, E and Gunter, MJ and Murphy, N},
doi = {10.1158/1055-9965.EPI-20-1218},
journal = {Cancer Epidemiology, Biomarkers and Prevention},
pages = {953--964},
title = {Causal effects of lifetime smoking on breast and colorectal cancer risk: Mendelian randomization study},
url = {http://dx.doi.org/10.1158/1055-9965.EPI-20-1218},
volume = {30},
year = {2021}
}

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TY  - JOUR
AB  - 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 [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]. 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.
AU  - Dimou,N
AU  - Yarmolinsky,J
AU  - Bouras,E
AU  - Tsilidis,KK
AU  - Martin,RM
AU  - Lewis,SJ
AU  - Gram,IT
AU  - Bakker,MF
AU  - Brenner,H
AU  - Figueiredo,JC
AU  - Fortner,RT
AU  - Gruber,SB
AU  - Van,Guelpen B
AU  - Hsu,L
AU  - Kaaks,R
AU  - Kweon,S-S
AU  - Lin,Y
AU  - Lindor,NM
AU  - Newcomb,PA
AU  - Sanchez-Perez,M-J
AU  - Severi,G
AU  - Tindle,HA
AU  - Tumino,R
AU  - Weiderpass,E
AU  - Gunter,MJ
AU  - Murphy,N
DO  - 10.1158/1055-9965.EPI-20-1218
EP  - 964
PY  - 2021///
SN  - 1055-9965
SP  - 953
TI  - Causal effects of lifetime smoking on breast and colorectal cancer risk: Mendelian randomization study
T2  - Cancer Epidemiology, Biomarkers and Prevention
UR  - http://dx.doi.org/10.1158/1055-9965.EPI-20-1218
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33653810
UR  - https://cebp.aacrjournals.org/content/30/5/953
UR  - http://hdl.handle.net/10044/1/88262
VL  - 30
ER  -

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