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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]

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