Association of a Germline KRAS Exon 2 (codon-12 region) Variant with Cervical Cancer Risk in Eastern Algeria Women

Abstract

Background & Objective: Cervical cancer remains a major health concern worldwide. Beyond infectious causes, genetic factors such as KRAS mutations may play a role in cervical carcinogenesis. This study was conducted with aim to assess the association between the germline KRAS exon 2 (codon 12, c.35G>T; p.Gly12Val; rs121913529) variant and cervical cancer susceptibility in Eastern Algerian women.Materials & Methods: This case-control study was conducted on 97 women with histologically confirmed cervical cancer and 100 healthy controls. Genotyping of KRAS exon 2 was performed on leukocyte deoxyribonucleic acid using polymerase chain reaction followed by restriction fragment length polymorphism. Genotype and allele frequencies were compared, and logistic regression was applied to identify independent demographic, reproductive, and genetic risk factors.Results: The controls deviated from Hardy-Weinberg equilibrium, which may affect interpretation. The homozygous mutant genotype was detected exclusively in patients (P<0.0001). The mutant allele was significantly more frequent in cases than controls (43.3% vs. 26.5%; OR=2.12; 95% CI: 1.39-3.23; P<0.0001). Multivariate regression identified age <50 years (P=0.033), postmenopausal status (P<0.001), and higher parity (P=0.016) as independent predictors of cervical cancer.Conclusion: The germline KRAS exon 2 (codon-12 region) variant may contribute to genetic susceptibility to cervical cancer in this population. These findings are preliminary and highlight the need for larger, well-matched cohorts with detailed HPV genotyping to validate the association.