Meta-Analysis of Polymorphic Variants Conferring Genetic Risk to Cervical Cancer in Indian Women Supports CYP1A1 as an Important Associated Locus

Objective: Association of multiple polymorphic variants with cervical cancer has been elucidated by severalcandidate gene based as well as genome-wide association studies. However, contradictory outcomes of those studieshave failed to estimate the true effect of the polymorphic variants on cervical cancer. Methods: Literature mining ofthe PubMed database was done to gather all the publications related to genetic association with cervical cancer in India.Out of 98 PubMed hits only 29 genetic association studies were selected for meta-analysis based on specific inclusioncriteria. A fixed-effect meta-analysis was performed to evaluate the overall association of the genetic polymorphismswith cervical cancer. Cochran’s Q test was performed to assess between study heterogeneity. Publication bias wasalso estimated by funnel plots and Egger’s regression test. Further, sub-group analysis was conducted by fixed-effectmeta-regression to assess the impact of polymorphisms on cervical cancer in the presence of Human Papilloma Virus(HPV). Result: Following a fixed-effect model, meta-analysis was conducted that revealed 2 polymorphic variantsviz. ‘deletion polymorphism (Del2) (OR=1.79, 95% CI= 1.08-2.95, P=0.023) in GSTM1’ and ‘rs1048943 (OR = 2.34,95% CI=1.37-3.99, P=0.0018) in CYP1A1’ to be associated with cervical cancer. However, multiple testing correctionshowed only rs1048943 of CYP1A1 to be significantly associated (P-value=0.029) with cervical cancer with significantpublication bias (P-value=0.0113) as estimated by Egger’s regression test. The polymorphic variants ‘rs1801131’,‘rs1801133’, ‘rs2430561’, ‘rs1799782’, ‘rs25486’ and ‘rs25487’ showed significant (p<0.05) evidence of heterogeneitybetween studies by Cochran’s Q test and also by heterogeneity index (I2) calculation. Conclusion: Therefore, our studyrevealed significant association of rs1048943 in CYP1A1, but a nominal association of deletion polymorphism (Del2)in GSTM1 with cervical cancer, which provides a comprehensive insight on the true effect of the polymorphisms,reported in various case-control studies, on the risk of the development of cervical cancer in Indian women.