Common variants in LSP1, 2q35 and 8q24 and breast cancer risk for BRCA1 and BRCA2 mutation carriersShow others and affiliations
2009 (English)In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 18, no 22, p. 4442-4456Article in journal (Refereed) Published
Abstract [en]
Genome-wide association studies of breast cancer have identified multiple single nucleotide polymorphisms (SNPs) that are associated with increased breast cancer risks in the general population. In a previous study, we demonstrated that the minor alleles at three of these SNPs, in FGFR2, TNRC9 and MAP3K1, also confer increased risks of breast cancer for BRCA1 or BRCA2 mutation carriers. Three additional SNPs rs3817198 at LSP1, rs13387042 at 2q35 and rs13281615 at 8q24 have since been reported to be associated with breast cancer in the general population, and in this study we evaluated their association with breast cancer risk in 9442 BRCA1 and 5665 BRCA2 mutation carriers from 33 study centres. The minor allele of rs3817198 was associated with increased breast cancer risk only for BRCA2 mutation carriers [hazard ratio (HR) = 1.16, 95% CI: 1.07-1.25, P-trend = 2.8 × 10-4]. The best fit for the association of SNP rs13387042 at 2q35 with breast cancer risk was a dominant model for both BRCA1 and BRCA2 mutation carriers (BRCA1: HR = 1.14, 95% CI: 1.04-1.25, P = 0.0047; BRCA2: HR = 1.18 95% CI: 1.04-1.33, P = 0.0079). SNP rs13281615 at 8q24 was not associated with breast cancer for either BRCA1 or BRCA2 mutation carriers, but the estimated association for BRCA2 mutation carriers (per-allele HR = 1.06, 95% CI: 0.98-1.14) was consistent with odds ratio estimates derived from population-based case-control studies. The LSP1 and 2q35 SNPs appear to interact multiplicatively on breast cancer risk for BRCA2 mutation carriers. There was no evidence that the associations vary by mutation type depending on whether the mutated protein is predicted to be stable or not.
Place, publisher, year, edition, pages
Oxford University Press, 2009. Vol. 18, no 22, p. 4442-4456
Keywords [en]
BRCA1 protein, BRCA2 protein, oncoprotein, protein LSP1, unclassified drug, adult, aged, allele, article, breast cancer, cancer risk, controlled study, gene mutation, genetic association, heterozygote, human, priority journal, single nucleotide polymorphism, Aged, 80 and over, Breast Neoplasms, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 8, Female, Follow-Up Studies, Genetic Predisposition to Disease, Genetic Variation, Genetics, Population, Genome-Wide Association Study, Humans, Microfilament Proteins, Middle Aged, Mutation, Polymorphism, Single Nucleotide, Young Adult
National Category
Cancer and Oncology Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:hj:diva-39677DOI: 10.1093/hmg/ddp372ISI: 000271107300019Scopus ID: 2-s2.0-71049194443OAI: oai:DiVA.org:hj-39677DiVA, id: diva2:1212088
Note
The Swedish BRCA1 and BRCA2 Study (SWE-BRCA)
SWE-BRCA collaborators: P.K., Margareta Nordling, Annika Bergman and Zakaria Einbeigi, Gothenburg, Sahlgrenska University Hospital; Marie Stenmark-Askmalm and Sigrun Liedgren, Linkoping University Hospital; Ake Borg, Niklas Loman, Hakan Olsson, Ulf Kristoffersson, Helena Jernstrom, K.H. and Karin Henrisson, Lund University Hospital; Annika Lindblom, Brita Arver, Anna von Wachenfeldt, Annelie Liljegren, G.B.-B. and J.R., Stockholm, Karolinska. University Hospital; Beatrice Malmer, Eva-Lena Stattin and Monica Emanuelsson, Umea University Hospital; H.E., Richard Rosenquist Brandell and Niklas Dahl, Uppsala University Hospital.
2018-06-012018-06-012018-06-01Bibliographically approved