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. 2019 Jul;121(2):180-192.
doi: 10.1038/s41416-019-0492-8. Epub 2019 Jun 19.

Mendelian Randomisation Study of Height and Body Mass Index as Modifiers of Ovarian Cancer Risk in 22,588 BRCA1 and BRCA2 Mutation Carriers

Frank Qian  1 Matti A Rookus  2 Goska Leslie  3 Harvey A Risch  4 Mark H Greene  5 Cora M Aalfs  6 Muriel A Adank  7 Julian Adlard  8 Bjarni A Agnarsson  9   10 Munaza Ahmed  11 Kristiina Aittomäki  12 Irene L Andrulis  13   14 Norbert Arnold  15   16 Banu K Arun  17 Margreet G E M Ausems  18 Jacopo Azzollini  19 Daniel Barrowdale  3 Julian Barwell  20 Javier Benitez  21   22 Katarzyna Białkowska  23 Valérie Bonadona  24 Julika Borde  25   26   27 Ake Borg  28 Angela R Bradbury  29 Joan Brunet  30 Saundra S Buys  31 Trinidad Caldés  32 Maria A Caligo  33 Ian Campbell  34   35 Jonathan Carter  36 Jocelyne Chiquette  37 Wendy K Chung  38 Kathleen B M Claes  39 J Margriet Collée  40 Marie-Agnès Collonge-Rame  41 Fergus J Couch  42 Mary B Daly  43 Capucine Delnatte  44 Orland Diez  45 Susan M Domchek  29 Cecilia M Dorfling  46 Jacqueline Eason  47 Douglas F Easton  3   48 Ros Eeles  49 Christoph Engel  50 D Gareth Evans  51   52 Laurence Faivre  53   54 Lidia Feliubadaló  55 Lenka Foretova  56 Eitan Friedman  57   58 Debra Frost  3 Patricia A Ganz  59 Judy Garber  60 Vanesa Garcia-Barberan  31 Andrea Gehrig  61 Gord Glendon  13 Andrew K Godwin  62 Encarna B Gómez Garcia  63 Ute Hamann  64 Jan Hauke  24   25   26 John L Hopper  65 Peter J Hulick  66   67 Evgeny N Imyanitov  68 Claudine Isaacs  69 Louise Izatt  70 Anna Jakubowska  22   71 Ramunas Janavicius  72   73 Esther M John  74 Beth Y Karlan  75 Carolien M Kets  76 Yael Laitman  57 Conxi Lázaro  55 Dominique Leroux  77 Jenny Lester  75 Fabienne Lesueur  78   79 Jennifer T Loud  5 Jan Lubiński  23 Alicja Łukomska  23 Lesley McGuffog  3 Noura Mebirouk  78   79   80 Hanne E J Meijers-Heijboer  81 Alfons Meindl  82 Austin Miller  83 Marco Montagna  84 Thea M Mooij  2 Emmanuelle Mouret-Fourme  85 Katherine L Nathanson  29 Bita Nehoray  86 Susan L Neuhausen  87 Heli Nevanlinna  88 Finn C Nielsen  89 Kenneth Offit  90   91 Edith Olah  92 Kai-Ren Ong  93 Jan C Oosterwijk  94 Laura Ottini  95 Michael T Parsons  96 Paolo Peterlongo  97 Georg Pfeiler  98 Nisha Pradhan  90 Paolo Radice  99 Susan J Ramus  100   101 Johanna Rantala  102 Gad Rennert  103 Mark Robson  91 Gustavo C Rodriguez  104 Ritu Salani  105 Maren T Scheuner  106 Rita K Schmutzler  26   27 Payal D Shah  29 Lucy E Side  107 Jacques Simard  108 Christian F Singer  98 Doris Steinemann  109 Dominique Stoppa-Lyonnet  85   110   111 Yen Yen Tan  98 Manuel R Teixeira  112   113 Mary Beth Terry  114 Mads Thomassen  115 Marc Tischkowitz  116   117 Silvia Tognazzo  84 Amanda E Toland  118 Nadine Tung  119 Christi J van Asperen  120 Klaartje van Engelen  121 Elizabeth J van Rensburg  46 Laurence Venat-Bouvet  122 Jeroen Vierstraete  39 Gabriel Wagner  98 Lisa Walker  123 Jeffrey N Weitzel  86 Drakoulis Yannoukakos  124 KConFab InvestigatorsHEBON InvestigatorsGEMO Study CollaboratorsEMBRACE CollaboratorsAntonis C Antoniou  3 David E Goldgar  125 Olufunmilayo I Olopade  126 Georgia Chenevix-Trench  96 Timothy R Rebbeck  127   128 Dezheng Huo  129   130 CIMBA
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Free PMC article

Mendelian Randomisation Study of Height and Body Mass Index as Modifiers of Ovarian Cancer Risk in 22,588 BRCA1 and BRCA2 Mutation Carriers

Frank Qian et al. Br J Cancer. .
Free PMC article

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 (Pinteraction < 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.

Conflict of interest statement

G.P. received honoraria and grant from Pfizer, Roche, Novartis, Accord, AstraZeneca, Amgen, Accord and Lilly. R.S. served on advisory board for Tesaro, Clovis, Astra Zeneca, Ethicon and Genmab, and speaker’s bureau for Tesaro and Genentech. The other authors declare no competing interests.

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