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Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2014 Oct 21. pii: 1055-9965.EPI-14-0532. doi: 10.1158/1055-9965.EPI-14-0532. pmc: PMC4294951. mid: NIHMS644448

Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.

Peterlongo P¹, Chang-Claude J², Moysich KB³, Rudolph A⁴, Schmutzler RK⁵, Simard J⁶, Soucy P⁷, Eeles RA⁸, Easton DF⁹, Hamann U¹⁰, Wilkening S¹¹, Chen B¹², Rookus MA¹³, Schmidt MK¹⁴, van der Baan FH¹⁵, Spurdle AB¹⁶, Walker LC¹⁷, Lose F¹⁸, Maia AT¹⁹, Montagna M²⁰, Matricardi L²¹, Lubinski J²², Jakubowska A²³, Gómez Garcia EB²⁴, Olopade OI²⁵, Nussbaum RL²⁶, Nathanson KL²⁷, Domchek SM²⁸, Rebbeck TR²⁹, Arun BK³⁰, Karlan BY³¹, Orsulic S³², Lester J³³, Chung WK³⁴, Miron A³⁵, Southey MC³⁶, Goldgar DE³⁷, Buys SS³⁸, Janavicius R³⁹, Dorfling CM⁴⁰, van Rensburg EJ⁴¹, Ding YC⁴², Neuhausen SL⁴³, Hansen TV⁴⁴, Gerdes AM⁴⁵, Ejlertsen B⁴⁶, Jønson L⁴⁷, Osorio A⁴⁸, Martínez-Bouzas C⁴⁹, Benitez J⁵⁰, Conway EE⁵¹, Blazer KR⁵², Weitzel JN⁵³, Manoukian S⁵⁴, Peissel B⁵⁵, Zaffaroni D⁵⁶, Scuvera G⁵⁷, Barile M⁵⁸, Ficarazzi F⁵⁹, Mariette F⁶⁰, Fortuzzi S⁶¹, Viel A⁶², Giannini G⁶³, Papi L⁶⁴, Martayan A⁶⁵, Tibiletti MG⁶⁶, Radice P⁶⁷, Vratimos A⁶⁸, Fostira F⁶⁹, Garber JE⁷⁰, Donaldson A⁷¹, Brewer C⁷², Foo C⁷³, Evans DG⁷⁴, Frost D⁷⁵, Eccles D⁷⁶, Brady A⁷⁷, Cook J⁷⁸, Tischkowitz M⁷⁹, Adlard J⁸⁰, Barwell J⁸¹, Walker L⁸², Izatt L⁸³, Side LE⁸⁴, Kennedy MJ⁸⁵, Rogers MT⁸⁶, Porteous ME⁸⁷, Morrison PJ⁸⁸, Platte R⁸⁹, Davidson R⁹⁰, Hodgson SV⁹¹, Ellis S⁹², Cole T⁹³, Godwin AK⁹⁴, Claes K⁹⁵, Van Maerken T⁹⁶, Meindl A⁹⁷, Gehrig A⁹⁸, Sutter C⁹⁹, Engel C¹⁰⁰, Niederacher D¹⁰¹, Steinemann D¹⁰², Plendl H¹⁰³, Kast K¹⁰⁴, Rhiem K¹⁰⁵, Ditsch N¹⁰⁶, Arnold N¹⁰⁷, Varon-Mateeva R¹⁰⁸, Wappenschmidt B¹⁰⁹, Wang-Gohrke S¹¹⁰, Bressac-de Paillerets B¹¹¹, Buecher B¹¹², Delnatte C¹¹³, Houdayer C¹¹⁴, Stoppa-Lyonnet D¹¹⁵, Damiola F¹¹⁶, Coupier I¹¹⁷, Barjhoux L¹¹⁸, Venat-Bouvet L¹¹⁹, Golmard L¹²⁰, Boutry-Kryza N¹²¹, Sinilnikova OM¹²², Caron O¹²³, Pujol P¹²⁴, Mazoyer S¹²⁵, Belotti M¹²⁶, Piedmonte M¹²⁷, Friedlander ML¹²⁸, Rodriguez GC¹²⁹, Copeland LJ¹³⁰, de la Hoya M¹³¹, Segura PP¹³², Nevanlinna H¹³³, Aittomäki K¹³⁴, van Os TA¹³⁵, Meijers-Heijboer HE¹³⁶, van der Hout AH¹³⁷, Vreeswijk MP¹³⁸, Hoogerbrugge N¹³⁹, Ausems MG¹⁴⁰, van Doorn HC¹⁴¹, Collée JM¹⁴², Olah E¹⁴³, Diez O¹⁴⁴, Blanco I¹⁴⁵, Lazaro C¹⁴⁶, Brunet J¹⁴⁷, Feliubadalo L¹⁴⁸, Cybulski C¹⁴⁹, Gronwald J¹⁵⁰, Durda K¹⁵¹, Jaworska-Bieniek K¹⁵², Sukiennicki G¹⁵³, Arason A¹⁵⁴, Chiquette J¹⁵⁵, Teixeira MR¹⁵⁶, Olswold C¹⁵⁷, Couch FJ¹⁵⁸, Lindor NM¹⁵⁹, Wang X¹⁶⁰, Szabo CI¹⁶¹, Offit K¹⁶², Corines M¹⁶³, Jacobs L¹⁶⁴, Robson ME¹⁶⁵, Zhang L¹⁶⁶, Joseph V¹⁶⁷, Berger A¹⁶⁸, Singer CF¹⁶⁹, Rappaport C¹⁷⁰, Kaulich DG¹⁷¹, Pfeiler G¹⁷², Tea MK¹⁷³, Phelan CM¹⁷⁴, Greene MH¹⁷⁵, Mai PL¹⁷⁶, Rennert G¹⁷⁷, Mulligan AM¹⁷⁸, Glendon G¹⁷⁹, Tchatchou S¹⁸⁰, Andrulis IL¹⁸¹, Toland AE¹⁸², Bojesen A¹⁸³, Pedersen IS¹⁸⁴, Thomassen M¹⁸⁵, Jensen UB¹⁸⁶, Laitman Y¹⁸⁷, Rantala J¹⁸⁸, von Wachenfeldt A¹⁸⁹, Ehrencrona H¹⁹⁰, Askmalm MS¹⁹¹, Borg Å¹⁹², Kuchenbaecker KB¹⁹³, McGuffog L¹⁹⁴, Barrowdale D¹⁹⁵, Healey S¹⁹⁶, Lee A¹⁹⁷, Pharoah PD¹⁹⁸, Chenevix-Trench G¹⁹⁹, Antoniou AC²⁰⁰, Friedman E²⁰¹

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Abstract

BACKGROUND: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes.

METHODS: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach.

RESULTS: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments.

CONCLUSION: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.

IMPACT: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

Publikations ID: 25336561
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