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Cancer Epidemiol. 2013 Oct;37(5):639-46. doi: 10.1016/j.canep.2013.04.018. Epub 2013 Jun 18.

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

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1
Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), School of Basic Medical Sciences, Peking University Health Science Center, Beijing, PR China.

Abstract

INTRODUCTION:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

This study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may affect ovarian cancer susceptibility in Chinese Han women.

KEYWORDS:

AURKA; BRCA1; CCNE1; CDK2; Ovarian cancer; Single nucleotide polymorphism (SNP)

PMID:
23787073
DOI:
10.1016/j.canep.2013.04.018
[Indexed for MEDLINE]
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