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

Document Type: Systematic Review and Meta-analysis

Authors

1 Department of Genetics, University of Calcutta, Kolkata, India.

2 National Institute of Biomedical Genomics, Kalyani, India.

Abstract

Objective: Association of multiple polymorphic variants with cervical cancer has been elucidated by several
candidate gene based as well as genome-wide association studies. However, contradictory outcomes of those studies
have failed to estimate the true effect of the polymorphic variants on cervical cancer. Methods: Literature mining of
the 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 inclusion
criteria. A fixed-effect meta-analysis was performed to evaluate the overall association of the genetic polymorphisms
with cervical cancer. Cochran’s Q test was performed to assess between study heterogeneity. Publication bias was
also estimated by funnel plots and Egger’s regression test. Further, sub-group analysis was conducted by fixed-effect
meta-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 variants
viz. ‘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 correction
showed only rs1048943 of CYP1A1 to be significantly associated (P-value=0.029) with cervical cancer with significant
publication 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 heterogeneity
between studies by Cochran’s Q test and also by heterogeneity index (I2) calculation. Conclusion: Therefore, our study
revealed 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.

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