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

Khanra, Kalyani; Panda, Kakali; Bhattacharya, Chandan; Mitra, A.K.; Sarkar, Ranu; Bhattacharyya, Nandan

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자료유형: 학술저널

저자정보: Khanra, Kalyani (Department of Biotechnology, Haldia Institute of Technology) Panda, Kakali (Department of Biotechnology, Haldia Institute of Technology) Bhattacharya, Chandan (Bidhan Chandra Krishi Vishyavidyalaya, Regional Research Station) Mitra, A.K. (Haldia Seva Sadan) Sarkar, Ranu (Department of Pathology, NRS Medical College) Bhattacharyya, Nandan (Department of Biotechnology, Haldia Institute of Technology)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제13권 제4호

발행연도: 2012.1

수록면: 1,321 - 1,324 (4page)

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Background: DNA polymerase beta ($pol{\beta}$) is a key enzyme in the base excision repair pathway. It is 39kDa protein, 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 strand DNA binding activity, whereas exons VIII to XI account for the nucleotidyl transferase activity and exons XII to XIV the dNTP selection activity. Aim: To examine the association between $pol{\beta}$ polymorphisms and the risk of ovarian cancer, the present case control study was performed using 152 cancer samples and non-metastatic normal samples from the same patients. In this study, mutational analysis of $pol{\beta}$ genomic DNA was undertaken using primers from exons IX to XIV - the portion having catalytic activity. Results: We detected alteration in DNA polymerase beta by SSCP. Two specific heterozygous point mutations of $pol{\beta}$ were identified in Exon 9:486, A->C (polymorphism 1; 11.18%) and in Exon 11:676, A->C (polymorphism 2; 9.86%). The correlation study involving polymorphism 1 and 4 types of tissue showed a significant correlation between mucinous type with a Pearson correlation value of 4.03 (p=0.04). The association among polymorphism 2 with serous type and stage IV together have shown Pearson ${\chi}^2$ 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 for $pol{\beta}$ polymorphisms being a risk factor for ovarian carcinogenesis in India.

#DNA polymerase beta #DNA repair #somatic mutation #polymorphism #DNA-SSCP #India

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