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. 2019 Apr 1;111(4):350-364.
doi: 10.1093/jnci/djy132.

Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study

Frank Qian  1 Shengfeng Wang  2   3 Jonathan Mitchell  4 Lesley McGuffog  5 Daniel Barrowdale  5 Goska Leslie  5 Jan C Oosterwijk  6 Wendy K Chung  7 D Gareth Evans  8 Christoph Engel  9   10 Karin Kast  11   12 Cora M Aalfs  13   14   15 Muriel A Adank  16 Julian Adlard  17   12 Bjarni A Agnarsson  18   19 Kristiina Aittomäki  20 Elisa Alducci  21   12 Irene L Andrulis  22   23 Banu K Arun  24 Margreet G E M Ausems  25 Jacopo Azzollini  26 Emmanuelle Barouk-Simonet  27   28 Julian Barwell  29   30 Muriel Belotti  31 Javier Benitez  32 Andreas Berger  33 Ake Borg  34   35 Angela R Bradbury  36 Joan Brunet  31   37   38 Saundra S Buys  39 Trinidad Caldes  40 Maria A Caligo  41 Ian Campbell  42   43 Sandrine M Caputo  29   31 Jocelyne Chiquette  44 Kathleen B M Claes  45 J Margriet Collée  46 Fergus J Couch  47 Isabelle Coupier  48 Mary B Daly  49 Rosemarie Davidson  50 Orland Diez  51 Susan M Domchek  36 Alan Donaldson  52 Cecilia M Dorfling  53   54 Ros Eeles  55 Lidia Feliubadaló  56 Lenka Foretova  57   58 Jeffrey Fowler  59 Eitan Friedman  60   61 Debra Frost  5 Patricia A Ganz  32 Judy Garber  34 Vanesa Garcia-Barberan  40 Gord Glendon  22 Andrew K Godwin  28 Encarna B Gómez Garcia  12 Jacek Gronwald  12 Eric Hahnen  62 Ute HamannAlex Henderson  35 Carolyn B Hendricks  54 John L Hopper  56 Peter J Hulick  14   15 Evgeny N Imyanitov  51 Claudine Isaacs  63 Louise Izatt  64 Ángel Izquierdo  30 Anna Jakubowska  12 Katarzyna Kaczmarek  12 Eunyoung Kang  65 Beth Y Karlan  66 Carolien M Kets  67 Sung-Won Kim  68 Zisun Kim  69 Ava Kwong  70   71   72 Yael Laitman  60 Christine Lasset  73 Min Hyuk Lee  74 Jong Won Lee  75 Jihyoun Lee  12   66   74 Jenny Lester  12 Fabienne Lesueur  76   77   78   79 Jennifer T Loud  80 Jan Lubinski  12 Noura Mebirouk  76   77   78   79 Hanne E J Meijers-Heijboer  81 Alfons Meindl  82   83 Austin Miller  82 Marco Montagna  84 Thea M Mooij  85 Patrick J Morrison  86 Emmanuelle Mouret-Fourme  31 Katherine L NathansonSusan L Neuhausen  87 Heli Nevanlinna  88 Dieter Niederacher  89 Finn C Nielsen  90 Robert L Nussbaum  91 Kenneth Offit  92   93 Edith Olah  94 Kai-Ren Ong  95 Laura Ottini  96 Sue K Park  97 Paolo Peterlongo  98 Georg Pfeiler  99 Catherine M Phelan  100 Bruce Poppe  45 Nisha Pradhan  92 Paolo Radice  101 Susan J Ramus  102   103 Johanna Rantala  104 Mark Robson  93 Gustavo C Rodriguez  105 Rita K Schmutzler  62 Christina G Hutten Selkirk  14 Payal D Shah  36 Jacques Simard  106 Christian F Singer  107 Johanna Sokolowska  108 Dominique Stoppa-Lyonnet  109   110 Christian Sutter  111 Yen Yen Tan  38 R Manuel Teixeira  112   113 Soo H Teo  114   115 Mary Beth Terry  116 Mads Thomassen  117 Marc Tischkowitz  118   119 Amanda E Toland  120 Katherine M Tucker  121   122 Nadine Tung  123 Christi J van Asperen  124 Klaartje van Engelen  13 Elizabeth J van Rensburg  53 Shan Wang-Gohrke  125 Barbara Wappenschmidt  62 Jeffrey N Weitzel  126 Drakoulis Yannoukakos  127 GEMO Study CollaboratorsHEBONEMBRACEMark H Greene  80 Matti A Rookus  85 Douglas F Easton  5   128 Georgia Chenevix-Trench  129 Antonis C Antoniou  5 David E Goldgar  130 Olufunmilayo I Olopade  1 Timothy R Rebbeck  131   132 Dezheng Huo  1   133
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Free PMC article

Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study

Frank Qian et al. J Natl Cancer Inst. .
Free PMC article

Abstract

Background: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear.

Methods: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided.

Results: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer.

Conclusion: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.

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