Dataset Information

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

ABSTRACT:

Background

Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.

Methods

We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models.

Results

Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m² increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (P_interaction < 0.05).

Conclusion

Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

SUBMITTER: Qian F

PROVIDER: S-EPMC6738050 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

Qian Frank F Rookus Matti A MA Leslie Goska G Risch Harvey A HA Greene Mark H MH Aalfs Cora M CM Adank Muriel A MA Adlard Julian J Agnarsson Bjarni A BA Ahmed Munaza M Aittomäki Kristiina K Andrulis Irene L IL Arnold Norbert N Arun Banu K BK Ausems Margreet G E M MGEM Azzollini Jacopo J Barrowdale Daniel D Barwell Julian J Benitez Javier J Białkowska Katarzyna K Bonadona Valérie V Borde Julika J Borg Ake A Bradbury Angela R AR Brunet Joan J Buys Saundra S SS Caldés Trinidad T Caligo Maria A MA Campbell Ian I Carter Jonathan J Chiquette Jocelyne J Chung Wendy K WK Claes Kathleen B M KBM Collée J Margriet JM Collonge-Rame Marie-Agnès MA Couch Fergus J FJ Daly Mary B MB Delnatte Capucine C Diez Orland O Domchek Susan M SM Dorfling Cecilia M CM Eason Jacqueline J Easton Douglas F DF Eeles Ros R Engel Christoph C Evans D Gareth DG Faivre Laurence L Feliubadaló Lidia L Foretova Lenka L Friedman Eitan E Frost Debra D Ganz Patricia A PA Garber Judy J Garcia-Barberan Vanesa V Gehrig Andrea A Glendon Gord G Godwin Andrew K AK Gómez Garcia Encarna B EB Hamann Ute U Hauke Jan J Hopper John L JL Hulick Peter J PJ Imyanitov Evgeny N EN Isaacs Claudine C Izatt Louise L Jakubowska Anna A Janavicius Ramunas R John Esther M EM Karlan Beth Y BY Kets Carolien M CM Laitman Yael Y Lázaro Conxi C Leroux Dominique D Lester Jenny J Lesueur Fabienne F Loud Jennifer T JT Lubiński Jan J Łukomska Alicja A McGuffog Lesley L Mebirouk Noura N Meijers-Heijboer Hanne E J HEJ Meindl Alfons A Miller Austin A Montagna Marco M Mooij Thea M TM Mouret-Fourme Emmanuelle E Nathanson Katherine L KL Nehoray Bita B Neuhausen Susan L SL Nevanlinna Heli H Nielsen Finn C FC Offit Kenneth K Olah Edith E Ong Kai-Ren KR Oosterwijk Jan C JC Ottini Laura L Parsons Michael T MT Peterlongo Paolo P Pfeiler Georg G Pradhan Nisha N Radice Paolo P Ramus Susan J SJ Rantala Johanna J Rennert Gad G Robson Mark M Rodriguez Gustavo C GC Salani Ritu R Scheuner Maren T MT Schmutzler Rita K RK Shah Payal D PD Side Lucy E LE Simard Jacques J Singer Christian F CF Steinemann Doris D Stoppa-Lyonnet Dominique D Tan Yen Yen YY Teixeira Manuel R MR Terry Mary Beth MB Thomassen Mads M Tischkowitz Marc M Tognazzo Silvia S Toland Amanda E AE Tung Nadine N van Asperen Christi J CJ van Engelen Klaartje K van Rensburg Elizabeth J EJ Venat-Bouvet Laurence L Vierstraete Jeroen J Wagner Gabriel G Walker Lisa L Weitzel Jeffrey N JN Yannoukakos Drakoulis D Antoniou Antonis C AC Goldgar David E DE Olopade Olufunmilayo I OI Chenevix-Trench Georgia G Rebbeck Timothy R TR Huo Dezheng D

British journal of cancer 20190619 2

<h4>Background</h4>Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown.<h4>Methods</h4>We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created ...[more]

PMID: 31213659

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Project description:ObjectiveTo determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status.DesignMendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors.SettingUK Biobank.Participants119,669 men and women of British ancestry, aged between 37 and 73 years.Main outcome measuresAge completed full time education, degree level education, job class, annual household income, and Townsend deprivation index.ResultsIn the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6 × 10(-3)) lower annual household income in men and a £1890 (£1680 to £2100; P=6 × 10(-15)) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6 × 10(-7)), and a £1130 (£680 to £1580) higher annual household income (P=4 × 10(-8)). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m(2)) caused a £2940 (£1680 to £4200; P=1 × 10(-5)) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only.ConclusionsThese data support evidence that height and BMI play an important partial role in determining several aspects of a person's socioeconomic status, especially women's BMI for income and deprivation and men's height for education, income, and job class. These findings have important social and health implications, supporting evidence that overweight people, especially women, are at a disadvantage and that taller people, especially men, are at an advantage.

Dataset Information

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

Background

Methods

Results

Conclusion

Publications

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

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