Association between newly identified variant form of DNA polymerase beta Δ208–304 and ovarian cancer

Abstract

Background:

Base excision repair (BER) is a key pathway for maintaining genomic stability. A key enzyme in the BER pathway is DNA polymerase beta (polβ), which removes the deoxyribose phosphate group (dRP) and fills in the gap with a nucleotide after the DNA lesion is excised. It has been shown that more than thirty percent of breast, bladder, esophageal, colon, and gastric cancer samples studied so far have exhibited DNA polymerase beta mutation.

Aim:

To examine the association between polβ polymorphism and ovarian cancer, case control study was performed using one hundred fifty two cancer samples and non-metastatic normal samples from the same patients in Indian population.

Design:

The polβ polymorphism was studied in ovarian carcinoma tissues samples initially by RT-PCR followed by sequencing and then by western blot analysis.

Result:

A new type of variant was detected along with the WT allele (pol $\mathit{\beta }{\mathrm{\Delta }}_{208-304}$ ). Stage IV samples have shown a significant factor for cancer progression in ovarian cancer patients of India [OR=3.58; 95% CI (1.6–7.9); and p=0.001]. The association study involving serous type and the variant showed a tendency towards ovarian carcinogenesis [OR=1.57; 95% CI (0.8–3.1); p=0.19]. The western blot analysis result indicates that the specific deletion appears to be associated with disease progression.

Conclusion:

The result reveals that this variant form of polβ is a predisposing factor for stage IV ovarian cancer samples in Indian population.