Single nucleotide polymorphisms in miRNA binding sites and miRNA genes as breast/ovarian cancer risk modifiers in jewish high-risk women

Tair Kontorovich, Asaf Levy, Michael Korostishevsky, Uri Nir, Eitan Friedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

We hypothesized that aberrant gene silencing by miRNA may affect mutant BRCA penetrance. To test this notion, frequency of single nucleotide polymorphisms (SNPs; n = 42) within predicted miRNA binding sites or miRNA precursors were determined and compared in 363 BRCA1 mutation carriers: asymptomatic (n = 160), breast cancer (n = 140) and ovarian cancer (n = 63) patients, and in 125 BRCA2 mutation carriers: asymptomatic (n = 48), breast cancer (n = 58) and ovarian cancer (n = 19) patients. Overall, 16 of 42 SNPs were polymorphic, 11 had a minor allele frequency greater than 5% and 9 of them maintained the Hardy-Weinberg Equilibrium. Based on Cox regression and Kaplan-Meier analyses, statistically significant differences were noted in BRCA2 mutation carriers by health status in 3 SNPs: CC homozygosity at rs6505162 increased ovarian cancer risk (RR 2.77; p = 0.028; 95% CI, 1.11-6.9); heterozygote SNP carriers of rs11169571 had an ∼2 fold increased risk for developing breast/ovarian cancer, whereas heterozygotes of the rs895819 SNP had an ∼50% reduced risk for developing breast/ovarian cancer. This study provides preliminary evidence for another regulatory level of penetrance of deleterious mutations in cancer predisposition genes.

Original languageAmerican English
Pages (from-to)589-597
Number of pages9
JournalInternational Journal of Cancer
Volume127
Issue number3
DOIs
StatePublished - 1 Aug 2010
Externally publishedYes

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