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Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

Ramus, Susan J; Antoniou, Antonis C; Kuchenbaecker, Karoline B; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M; Healey, Sue and Barrowdale, Daniel, et al. (2012) In Human Mutation 33(4). p.690-702
Abstract

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218... (More)

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.

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Adult, BRCA1 Protein, BRCA2 Protein, Cohort Studies, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Middle Aged, Mutation, Odds Ratio, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Retrospective Studies
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Human Mutation
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33
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4
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13 pages
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John Wiley & Sons
external identifiers
  • scopus:84862792587
ISSN
1059-7794
DOI
10.1002/humu.22025
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English
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yes
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5457ce04-f166-461f-883c-1724a6210ed7
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2019-05-19 04:40:56
@article{5457ce04-f166-461f-883c-1724a6210ed7,
  abstract     = {<p>Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer.</p>},
  author       = {Ramus, Susan J and Antoniou, Antonis C and Kuchenbaecker, Karoline B and Soucy, Penny and Beesley, Jonathan and Chen, Xiaoqing and McGuffog, Lesley and Sinilnikova, Olga M and Healey, Sue and Barrowdale, Daniel and Lee, Andrew and Thomassen, Mads and Gerdes, Anne-Marie and Kruse, Torben A and Jensen, Uffe Birk and Skytte, Anne-Bine and Caligo, Maria A and Liljegren, Annelie and Lindblom, Annika and Olsson, Håkan and Kristoffersson, Ulf and Stenmark-Askmalm, Marie and Melin, Beatrice and Domchek, Susan M and Nathanson, Katherine L and Rebbeck, Timothy R and Jakubowska, Anna and Lubinski, Jan and Jaworska, Katarzyna and Durda, Katarzyna and Złowocka, Elżbieta and Gronwald, Jacek and Huzarski, Tomasz and Byrski, Tomasz and Cybulski, Cezary and Toloczko-Grabarek, Aleksandra and Osorio, Ana and Benitez, Javier and Duran, Mercedes and Tejada, Maria-Isabel and Hamann, Ute and Rookus, Matti and van Leeuwen, Flora E and Aalfs, Cora M and Meijers-Heijboer, Hanne E J and van Asperen, Christi J and van Roozendaal, K E P and Hoogerbrugge, Nicoline and Collée, J Margriet and Johannsson, Oskar Th and , },
  issn         = {1059-7794},
  keyword      = {Adult,BRCA1 Protein,BRCA2 Protein,Cohort Studies,Female,Genetic Predisposition to Disease,Heterozygote,Humans,Middle Aged,Mutation,Odds Ratio,Ovarian Neoplasms,Polymorphism, Single Nucleotide,Retrospective Studies},
  language     = {eng},
  number       = {4},
  pages        = {690--702},
  publisher    = {John Wiley & Sons},
  series       = {Human Mutation},
  title        = {Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers},
  url          = {http://dx.doi.org/10.1002/humu.22025},
  volume       = {33},
  year         = {2012},
}