Association of two polymorphisms of DNA polymerase beta in exon-9 and exon-11 with ovarian carcinoma in India.

Abstract

BACKGROUND:

DNA polymerase beta (polβ ) is a key enzyme in the base excision repair pathway. It is 39 kDa 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 polβ 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 polβ 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 polβ 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 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 for polβ polymorphisms being a risk factor for ovarian carcinogenesis in India.

• Authors: Kalyani Khanra, Kakali Panda, Chandan Bhattacharya, A K Mitra, Ranu Sarkar, Nandan Bhattacharyya
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 13 Issue 4 Pg. 1321-4 ( 2012) ISSN: 2476-762X [Electronic] Thailand
• PMID: 22799326 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Polymerase beta

Topics

• Adult
• Aged
• Carcinoma (genetics, pathology)
• Case-Control Studies
• Confidence Intervals
• DNA Mutational Analysis
• DNA Polymerase beta (genetics)
• Exons
• Female
• Humans
• India
• Likelihood Functions
• Middle Aged
• Neoplasm Staging
• Neoplasms, Cystic, Mucinous, and Serous (genetics, pathology)
• Odds Ratio
• Ovarian Neoplasms (genetics, pathology)
• Point Mutation
• Polymorphism, Genetic
• Young Adult