Dataset Information

Body mass index and breast cancer survival: a Mendelian randomization analysis.

ABSTRACT: Background:There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. Methods:We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results:BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95). Conclusions:Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.

SUBMITTER: Guo Q

PROVIDER: S-EPMC5837506 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Body mass index and breast cancer survival: a Mendelian randomization analysis.

Guo Qi Q Burgess Stephen S Turman Constance C Bolla Manjeet K MK Wang Qin Q Lush Michael M Abraham Jean J Aittomäki Kristiina K Andrulis Irene L IL Apicella Carmel C Arndt Volker V Barrdahl Myrto M Benitez Javier J Berg Christine D CD Blomqvist Carl C Bojesen Stig E SE Bonanni Bernardo B Brand Judith S JS Brenner Hermann H Broeks Annegien A Burwinkel Barbara B Caldas Carlos C Campa Daniele D Canzian Federico F Chang-Claude Jenny J Chanock Stephen J SJ Chin Suet-Feung SF Couch Fergus J FJ Cox Angela A Cross Simon S SS Cybulski Cezary C Czene Kamila K Darabi Hatef H Devilee Peter P Diver W Ryan WR Dunning Alison M AM Earl Helena M HM Eccles Diana M DM Ekici Arif B AB Eriksson Mikael M Evans D Gareth DG Fasching Peter A PA Figueroa Jonine J Flesch-Janys Dieter D Flyger Henrik H Gapstur Susan M SM Gaudet Mia M MM Giles Graham G GG Glendon Gord G Grip Mervi M Gronwald Jacek J Haeberle Lothar L Haiman Christopher A CA Hall Per P Hamann Ute U Hankinson Susan S Hartikainen Jaana M JM Hein Alexander A Hiller Louise L Hogervorst Frans B FB Holleczek Bernd B Hooning Maartje J MJ Hoover Robert N RN Humphreys Keith K Hunter David J DJ Hüsing Anika A Jakubowska Anna A Jukkola-Vuorinen Arja A Kaaks Rudolf R Kabisch Maria M Kataja Vesa V Knight Julia A JA Koppert Linetta B LB Kosma Veli-Matti VM Kristensen Vessela N VN Lambrechts Diether D Le Marchand Loic L Li Jingmei J Lindblom Annika A Lindström Sara S Lissowska Jolanta J Lubinski Jan J Machiela Mitchell J MJ Mannermaa Arto A Manoukian Siranoush S Margolin Sara S Marme Federik F Martens John W M JWM McLean Catriona C Menéndez Primitiva P Milne Roger L RL Marie Mulligan Anna A Muranen Taru A TA Nevanlinna Heli H Neven Patrick P Nielsen Sune F SF Nordestgaard Børge G BG Olson Janet E JE Perez Jose I A JIA Peterlongo Paolo P Phillips Kelly-Anne KA Poole Christopher J CJ Pylkäs Katri K Radice Paolo P Rahman Nazneen N Rüdiger Thomas T Rudolph Anja A Sawyer Elinor J EJ Schumacher Fredrick F Seibold Petra P Seynaeve Caroline C Shah Mitul M Smeets Ann A Southey Melissa C MC Tollenaar Rob A E M RAEM Tomlinson Ian I Tsimiklis Helen H Ulmer Hans-Ulrich HU Vachon Celine C van den Ouweland Ans M W AMW Van't Veer Laura J LJ Wildiers Hans H Willett Walter W Winqvist Robert R Zamora M Pilar MP Chenevix-Trench Georgia G Dörk Thilo T Easton Douglas F DF García-Closas Montserrat M Kraft Peter P Hopper John L JL Zheng Wei W Schmidt Marjanka K MK Pharoah Paul D P PDP

International journal of epidemiology 20171201 6

<h4>Background</h4>There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.<h4>Methods</h4>We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a B ...[more]

PMID: 29232439

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Project description:BACKGROUND:Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. METHODS:We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases? = ?46,325, controls? = ?42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. RESULTS:In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR]? = ?0.65 per 5 kg/m2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32?×?10-10). The associations were similar for both premenopausal (OR?? = ??0.44, 95% CI:0.31-0.62, p? = ?9.91?×?10-8) and postmenopausal breast cancer (OR? = ?0.57, 95%?CI: 0.46-0.71, p? = ?1.88?×?10-8). This association was replicated in the data from the DRIVE consortium (OR? = ?0.72, 95%?CI: 0.60-0.84, p?? = ??1.64?×?10-7). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p?<?0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. CONCLUSIONS:BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.

Dataset Information

Body mass index and breast cancer survival: a Mendelian randomization analysis.

Publications

Body mass index and breast cancer survival: a Mendelian randomization analysis.

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