Elucidation of Increased Cervical Cancer Risk Due to Polymorphisms in XRCC1 (R399Q and R194W), ERCC5 (D1104H), and...

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Genetic variations, specifically single nucleotide polymorphisms (SNPs), play a role in the development of cervical cancer.
• Identifying functional SNPs associated with cervical carcinogenesis is crucial for understanding disease risk and progression.

Approach:

• Literature mining identified 114 protein-coding polymorphisms relevant to cervical cancer.
• Functional assessment of SNPs using sequence-dependent tools and analysis of protein stability via sequence and structural data.
• Meta-analysis of 23 non-synonymous SNPs (nsSNPs) to evaluate their association with cervical cancer risk at the population level.

Key Points:

• Polymorphisms in DNA damage repair genes XRCC1 (rs25487, rs1799782) and ERCC5 (rs17655), and oxidative stress gene NQO1 (rs1800566) are significantly associated with increased cervical cancer risk.
• XRCC1 rs25487 and rs1799782 showed the highest risk in homozygous and recessive models, respectively.
• ERCC5 rs17655 and NQO1 rs1800566 demonstrated significant pooled odds ratios in homozygous and heterozygous models, respectively.

Conclusions:

• This study identified specific nsSNPs that are damaging, destabilize proteins, and are associated with an increased risk of cervical cancer.
• The findings highlight the role of genetic variations in DNA damage repair and oxidative stress pathways in cervical carcinogenesis.
• These identified SNPs can serve as potential biomarkers for cervical cancer risk assessment.