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

Peterlongo, Paolo; Chang-Claude, Jenny; Moysich, Kirsten B; Rudolph, Anja; Schmutzler, Rita K; Simard, Jacques; Soucy, Penny; Eeles, Rosalind A; Easton, Douglas F and Hamann, Ute, et al. (2015) In Cancer Epidemiology Biomarkers & Prevention 24(1). p.308-316
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 non-genetic 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... (More)
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 non-genetic 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 0.005-1.000. 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. (Less)
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Cancer Epidemiology Biomarkers & Prevention
volume
24
issue
1
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308 - 316
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American Association for Cancer Research
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  • pmid:25336561
  • wos:000348030700038
  • scopus:84921028142
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-14-0532
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English
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50738424-08a2-4dc6-ae15-0f049f6cdaf7 (old id 4733442)
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http://www.ncbi.nlm.nih.gov/pubmed/25336561?dopt=Abstract
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@article{50738424-08a2-4dc6-ae15-0f049f6cdaf7,
  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 non-genetic 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 0.005-1.000. 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.},
  author       = {Peterlongo, Paolo and Chang-Claude, Jenny and Moysich, Kirsten B and Rudolph, Anja and Schmutzler, Rita K and Simard, Jacques and Soucy, Penny and Eeles, Rosalind A and Easton, Douglas F and Hamann, Ute and Wilkening, Stefan and Chen, Bowang and Rookus, Matti A and Schmidt, Marjanka K and van der Baan, Frederieke H and Spurdle, Amanda B and Walker, Logan C and Lose, Felicity and Maia, Ana-Teresa and Montagna, Marco and Matricardi, Laura and Lubinski, Jan and Jakubowska, Anna and Gomez-Garcia, Encarna B and Olopade, Olufunmilayo I and Nussbaum, Robert L and Nathanson, Katherine L and Domchek, Susan M and Rebbeck, Timothy R and Arun, Banu K and Karlan, Beth Y and Orsulic, Sandra and Lester, Jenny and Chung, Wendy K and Miron, Alex and Southey, Melissa C and Goldgar, David E and Buys, Saundra S and Janavicius, Ramunas and Dorfling, Cecelia M and van Rensburg, Elizabeth J and Ding, Yuan Chun and Neuhausen, Susan L and Hansen, Thomas V O and Gerdes, Anne-Marie and Ejlertsen, Bent and Jønson, Lars and Osorio, Ana and Martinez-Bouzas, Cristina and Benitez, Javier and Conway, Edye E and Blazer, Kathleen R and Weitzel, Jeffrey N and Manoukian, Siranoush and Peissel, Bernard and Zaffaroni, Daniela and Scuvera, Giulietta and Barile, Monica and Ficarazzi, Filomena and Mariette, Frederique and Fortuzzi, Stefano and Viel, Alessandra and Giannini, Giuseppe and Papi, Laura and Martayan, Aline and Tibiletti, Maria Grazia and Radice, Paolo and Vratimos, Athanassios and Fostira, Florentia and Garber, Judy E and Donaldson, Alan and Brewer, Carole and Foo, Claire and Evans, D Gareth R and Frost, Debra and Eccles, Diana and Brady, Angela and Cook, Jackie and Tischkowitz, Marc and Adlard, Julian and Barwell, Julian and Walker, Lisa and Izatt, Louise and Side, Lucy E and Kennedy, M John and Rogers, Mark T and Porteous, Mary E and Morrison, Patrick J and Platte, Radka and Davidson, Rosemarie and Hodgson, Shirley V and Ellis, Steve and Cole, Trevor and Godwin, Andrew K and Claes, Kathleen and Van Maerken, Tom and Meindl, Alfons and Gehrig, Andrea and Sutter, Christian and Engel, Christoph and Niederacher, Dieter and Steinemann, Doris and Plendl, Hansjoerg and Kast, Karin and Rhiem, Kerstin and Ditsch, Nina and Arnold, Norbert and Varon-Mateeva, Raymonda and Wappenschmidt, Barbara and Wang-Gohrke, Shan and Bressac-de Paillerets, Brigitte and Buecher, Bruno and Delnatte, Capucine and Houdayer, Claude and Stoppa-Lyonnet, Dominique and Damiola, Francesca and Coupier, Isabelle and Barjhoux, Laure and Venat-Bouvet, Laurence and Golmard, Lisa and Boutry-Kryza, Nadia and Sinilnikova, Olga M and Caron, Olivier and Pujol, Pascal and Mazoyer, Sylvie and Belotti, Muriel and Piedmonte, Marion and Friedlander, Michael L and Rodriguez, Gustavo C and Copeland, Larry J and de la Hoya, Miguel and Perez Segura, Pedro and Nevanlinna, Heli and Aittomäki, Kristiina and van Os, Theo A M and Meijers-Heijboer, Hanne E J and Van der Hout, Annemarie H and Vreeswijk, Maaike P G and Hoogerbrugge, Nicoline and Ausems, Margreet G E M and Van Doorn, Helena C and Collée, J Margriet and Olah, Edith and Díez, Orland and Blanco, Ignacio and Lazaro, Conxi and Brunet, Joan and Feliubadaló, Lídia and Cybulski, Cezary and Gronwald, Jacek and Durda, Katarzyna and Jaworska-Bieniek, Katarzyna and Sukiennicki, Grzegorz and Arason, Adalgeir and Chiquette, Jocelyne and Teixeira, Manuel R and Olswold, Curtis and Couch, Fergus J and Lindor, Noralane M and Wang, Xianshu and Szabo, Csilla I and Offit, Kenneth and Corines, Marina and Jacobs, Lauren and Robson, Mark and Zhang, Liying and Joseph, Vijai and Berger, Andreas and Singer, Christian F and Rappaport, Christine and Geschwantler Kaulich, Daphne and Pfeiler, Georg and Tea, Muy-Kheng M and Phelan, Catherine M and Greene, Mark H and Mai, Phuong L and Rennert, Gad and Mulligan, Anna Marie and Glendon, Gord and Tchatchou, Sandrine and Andrulis, Irene L and Toland, Amanda Ewart and Bojesen, Anders and Pedersen, Inge Sokilde and Thomassen, Mads and Jensen, Uffe Birk and Laitman, Yael and Rantala, Johanna and von Wachenfeldt, Anna and Ehrencrona, Hans and Stenmark Askmalm, Marie and Borg, Åke and Kuchenbaecker, Karoline B and McGuffog, Lesley and Barrowdale, Daniel and Healey, Sue and Lee, Andrew and Pharoah, Paul D P and Chenevix-Trench, Georgia and Antoniou, Antonis C and Friedman, Eitan},
  issn         = {1538-7755},
  language     = {eng},
  number       = {1},
  pages        = {308--316},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-14-0532},
  volume       = {24},
  year         = {2015},
}