Mendelian randomisation study of smoking exposure in relation to breast cancer risk.
Park HA., Neumeyer S., Michailidou K., Bolla MK., Wang Q., Dennis J., Ahearn TU., Andrulis IL., Anton-Culver H., Antonenkova NN., Arndt V., Aronson KJ., Augustinsson A., Baten A., Beane Freeman LE., Becher H., Beckmann MW., Behrens S., Benitez J., Bermisheva M., Bogdanova NV., Bojesen SE., Brauch H., Brenner H., Brucker SY., Burwinkel B., Campa D., Canzian F., Castelao JE., Chanock SJ., Chenevix-Trench G., Clarke CL., NBCS Collaborators None., Conroy DM., Couch FJ., Cox A., Cross SS., Czene K., Daly MB., Devilee P., Dörk T., Dos-Santos-Silva I., Dwek M., Eccles DM., Eliassen AH., Engel C., Eriksson M., Evans DG., Fasching PA., Flyger H., Fritschi L., García-Closas M., García-Sáenz JA., Gaudet MM., Giles GG., Glendon G., Goldberg MS., Goldgar DE., González-Neira A., Grip M., Guénel P., Hahnen E., Haiman CA., Håkansson N., Hall P., Hamann U., Han S., Harkness EF., Hart SN., He W., Heemskerk-Gerritsen BAM., Hopper JL., Hunter DJ., ABCTB Investigators None., kConFab Investigators None., Jager A., Jakubowska A., John EM., Jung A., Kaaks R., Kapoor PM., Keeman R., Khusnutdinova E., Kitahara CM., Koppert LB., Koutros S., Kristensen VN., Kurian AW., Lacey J., Lambrechts D., Le Marchand L., Lo W-Y., Lubiński J., Mannermaa A., Manoochehri M., Margolin S., Martinez ME., Mavroudis D., Meindl A., Menon U., Milne RL., Muranen TA., Nevanlinna H., Newman WG., Nordestgaard BG., Offit K., Olshan AF., Olsson H., Park-Simon T-W., Peterlongo P., Peto J., Plaseska-Karanfilska D., Presneau N., Radice P., Rennert G., Rennert HS., Romero A., Saloustros E., Sawyer EJ., Schmidt MK., Schmutzler RK., Schoemaker MJ., Schwentner L., Scott C., Shah M., Shu X-O., Simard J., Smeets A., Southey MC., Spinelli JJ., Stevens V., Swerdlow AJ., Tamimi RM., Tapper WJ., Taylor JA., Terry MB., Tomlinson I., Troester MA., Truong T., Vachon CM., van Veen EM., Vijai J., Wang S., Wendt C., Winqvist R., Wolk A., Ziogas A., Dunning AM., Pharoah PDP., Easton DF., Zheng W., Kraft P., Chang-Claude J.
BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.