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 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.


OBJECTIVE
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.


CONCLUSIONS
Hence, the results indicate that there is a tendency for polβ polymorphisms being a risk factor for ovarian carcinogenesis in India.
Department of Biotechnology, Haldia Institute of Technology, Haldia, India.
Kalyani
K
Khanra
Kakali
K
Panda
Chandan
C
Bhattacharya
A K
AK
Mitra
Ranu
R
Sarkar
Nandan
N
Bhattacharyya
D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D016001:Confidence Intervals; D004252:DNA Mutational Analysis; D019951:DNA Polymerase beta / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D007194:India; D016013:Likelihood Functions; D008875:Middle Aged; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics* / Q000473:pathology*; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D017354:Point Mutation; D011110:Polymorphism, Genetic; D055815:Young Adult
D019951:DNA Polymerase beta