Association of Two Polymorphisms of DNA Polymerase Beta in Exon-9 and Exon-11 with Ovarian Carcinoma in India

Background: DNA polymerase beta (polβ) is a key enzyme in the base excision repair pathway. It is 39kDaprotein, with two subunits, one large subunit of 31 kDa having catalytic activity between exon V to exon XIV,and an 8 kDa smaller subunit having single strand DNA binding activity. Exons V to VII have double strandDNA binding activity, whereas exons VIII to XI account for the nucleotidyl transferase activity and exons XIIto XIV the dNTP selection activity. Aim: To examine the association between polβ polymorphisms and the riskof ovarian cancer, the present case control study was performed using 152 cancer samples and non-metastaticnormal samples from the same patients. In this study, mutational analysis of polβ genomic DNA was undertakenusing primers from exons IX to XIV - the portion having catalytic activity.
Results: We detected alteration inDNA polymerase beta by SSCP. Two specific heterozygous point mutations of polβ were identified in Exon9:486, A->C (polymorphism 1; 11.18%) and in Exon 11:676, A->C (polymorphism 2; 9.86%). The correlationstudy involving polymorphism 1 and 4 types of tissue showed a significant correlation between mucinous typewith a Pearson correlation value of 4.03 (p=0.04). The association among polymorphism 2 with serous type andstage IV together have shown Pearson χ2 value of 3.28 with likelihood ratio of 4.4 (p=0.07) with OR =2.08 (0.3-14.55). This indicates that there is a tendency of correlation among polymorphism 2, serous type and stage IV,indicating a risk factor for ovarian cancer.
Conclusion: Hence, the results indicate that there is a tendency forpolβ polymorphisms being a risk factor for ovarian carcinogenesis in India.