A single nucleotide polymorphism in the 5 ' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers Journal Article
| Authors: | Wang, W. W.; Spurdle, A. B.; Kolachana, P.; Bove, B.; Modan, B.; Ebbers, S. M.; Suthers, G.; Tucker, M. A.; Kaufman, D. J.; Doody, M. M.; Tarone, R. E.; Daly, M.; Levavi, H.; Pierce, H.; Chetrit, A.; Yechezkel, G. H.; Chenevix-Trench, G.; Offit, K.; Godwin, A. K.; Struewing, J. P. |
| Article Title: | A single nucleotide polymorphism in the 5 ' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers |
| Abstract: | RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a "c" allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 "c" allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the "c" allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown. |
| Keywords: | sequence; protein; repair; breast-cancer; families; repeat; genetic-heterogeneity |
| Journal Title: | Cancer Epidemiology Biomarkers and Prevention |
| Volume: | 10 |
| Issue: | 9 |
| ISSN: | 1055-9965 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2001-09-01 |
| Start Page: | 955 |
| End Page: | 960 |
| Language: | English |
| ACCESSION: | WOS:000170899000007 |
| PROVIDER: | wos |
| PUBMED: | 11535547 |
| Notes: | Article -- Source: Wos |
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