Role of DNA repair and cell cycle control genes in ovarian cancer susceptibility
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Role of DNA repair and cell cycle control genes in ovarian cancer susceptibility Faten Zahran Mohamed • Yousry Mostafa Hussien • Mohamad Mohamad AlBakry • Randa H. Mohamed Noha Mohamed Said
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Received: 24 May 2012 / Accepted: 18 December 2012 / Published online: 1 January 2013 Ó Springer Science+Business Media Dordrecht 2012
Abstract Recent studies have identified several single nucleotide polymorphisms (SNPs) in the population that are associated with variations in the risks of many different cancer diseases. For ovarian cancer, the known highly penetrant susceptibility genes (BRCA1 and BRCA2) are probably responsible for only 40 % of the excess familial ovarian cancer risks, suggesting that other susceptibility genes of lower penetrance exist. The aim of the present study was to evaluate the role of SNPs in three genes, XRCC2 (R188H), ERCC2 (K751Q) and CDKN1B (V109G) which are with moderate risk for ovarian cancer susceptibility in Egyptian women. We further investigated the potential combined effect of these genes variants on ovarian cancer risk. The three genes polymorphisms were characterized in 100 ovarian cancer Egyptian females and 100 healthy women by (RFLP–PCR) method in a case control study. Our results revealed that the frequencies of AC genotypes of ERCC2 (K751Q), and GG genotypes of CDKN1B (V109G) polymorphisms were significantly higher in EOC patients than in normal individual (P = 0.007, 0.02 respectively). The frequencies of AA genotype of XRCC2 (R188H) and CC genotype of ERCC2 (K751Q) were higher in EOC patients than in normal
F. Z. Mohamed N. M. Said (&) Biochemistry Division, Chemistry Department, Faculty of Sciences, Zagazig University, Zagazig, Egypt e-mail: [email protected] Y. M. Hussien R. H. Mohamed Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt M. M. AlBakry Obstetric and Gynecology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
individual but without significance (P = 0.06, 0.38 respectively). Also, no association between any one of the three studied genes polymorphisms and the clinical characteristics of disease. The combination of GA (XRCC2) ? AC (ERCC2) ? GG (CDKN1B) was significantly associated with increased EOC risk. Also, the combination for GA (XRCC2) ? AC (ERCC2) and the combination of AA (XRCC2) ? CC (ERCC2) were significantly associated with increased EOC risk. There was significant difference in CA125 values between EOC and control Group (P \ 0.001). Our results suggested that, XRCC2, ERCC2 and CDKN1B genes are important candidate genes for susceptibility to EOC. Also, gene–gene interaction between GA (XRCC2) ? AC (ERCC2) ? GG (CDKN1B) polymorphism may be associated with increased risk of EOCC in Egyptian women. Keywords Ovarian cancer XRCC2 ERCC2 CDKN1B RFLP–PCR
Introduction One of the strongest risk factors for ovarian cancer is a family history of the disease; a woman with a single first degree relative diagnosed with ovarian cancer has a two to threefold increased risk [1]. This could be due
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