Genetic polymorphisms in AURKA, BRCA1, CCNE1 and CDK2 are associated with ovarian cancer susceptibility among Chinese Han women.

Centrosome aberrations and cell-cycle deregulation have important implications for ovarian cancer development. The AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation.,Using a haplotype-based analysis, this study aimed to investigate whether genetic polymorphisms in these four genes may contribute to ovarian cancer susceptibility. A total of 22 single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 287 cases of ovarian serous cystadenocarcinomas and 618 age-matched cancer-free controls from the Chinese Han population, and then haplotype blocks were reconstructed according to our genotyping data and linkage disequilibrium (LD) status of these SNPs.,For AURKA, we found that haplotype GA [rs6064391 (T→G)+rs911162 (G→A)] was strongly associated with decreased ovarian cancer risk (adjusted OR=0.31, 95% CI=0.15-0.63, P=0.0012). For BRCA1, we found that haplotype CGTAG was associated with decreased ovarian cancer risk (adjusted OR=0.64, 95% CI=0.41-0.98, P=0.0417). Moreover, women harboring homozygous GA/CGTAG haplotypes showed the lowest risk (OR=0.12, 95% CI=0.02-0.94, P=0.0438). In CCNE1, the SNPs rs3218035 and rs3218042 were significantly associated with increased ovarian cancer risk (rs3218035: adjusted OR=5.20, 95% CI=1.85-14.52, P=0.0017; rs3218042: adjusted OR=4.98, 95% CI=1.75-14.19, P=0.0027). For CDK2, no significant association was found.,This study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may affect ovarian cancer susceptibility in Chinese Han women.