TY - JOUR
T1 - Candidate genetic modifiers for breast and ovarian cancer risk inBRCA1andBRCA2 mutation carriers
AU - On Behalf Of Gemo Study Collaborators
AU - Peterlongo, Paolo
AU - Chang-Claude, Jenny
AU - Moysich, Kirsten B.
AU - Rudolph, Anja
AU - Schmutzler, Rita K.
AU - Simard, Jacques
AU - Soucy, Penny
AU - Eeles, Rosalind A.
AU - Easton, Douglas F.
AU - Hamann, Ute
AU - Wilkening, Stefan
AU - Chen, Bowang
AU - Rookus, Matti A.
AU - Schmidt, Marjanka K.
AU - Van Der Baan, Frederieke H.
AU - Spurdle, Amanda B.
AU - Walker, Logan C.
AU - Lose, Felicity
AU - Maia, Ana Teresa
AU - Montagna, Marco
AU - Matricardi, Laura
AU - Lubinski, Jan
AU - Jakubowska, Anna
AU - Garcia, Encarna B.Gómez
AU - Olopade, Olufunmilayo I.
AU - Nussbaum, Robert L.
AU - Nathanson, Katherine L.
AU - Domchek, Susan M.
AU - Rebbeck, Timothy R.
AU - Arun, Banu K.
AU - Karlan, Beth Y.
AU - Orsulic, Sandra
AU - Lester, Jenny
AU - Chung, Wendy K.
AU - Miron, Alex
AU - Southey, Melissa C.
AU - Goldgar, David E.
AU - Buys, Saundra S.
AU - Janavicius, Ramunas
AU - Dorfling, Cecilia M.
AU - Van Rensburg, Elizabeth J.
AU - Ding, Yuan Chun
AU - Neuhausen, Susan L.
AU - Hansen, Thomas V.O.
AU - Gerdes, Anne Marie
AU - Ejlertsen, Bent
AU - Jønson, Lars
AU - Osorio, Ana
AU - Martínez-Bouzas, Cristina
AU - Benitez, Javier
N1 - Publisher Copyright:
© 2014 American Association for Cancer Research.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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 inmany 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 analysiswas 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.
AB - 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 inmany 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 analysiswas 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.
UR - https://www.scopus.com/pages/publications/84921028142
U2 - 10.1158/1055-9965.EPI-14-0532
DO - 10.1158/1055-9965.EPI-14-0532
M3 - Article
C2 - 25336561
AN - SCOPUS:84921028142
SN - 1055-9965
VL - 24
SP - 308
EP - 316
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 1
ER -