Title : Impact of matrix metalloproteinase [MMP]-2 (2735C>T) and tissue inhibitor of metalloproteinase [TIMP]-2 (2418G>C) gene polymorphisms with human papillomavirus-mediated cervical cancer: Emerging trends in Gynecologic Oncology
Abstract:
Objectives: Inflammation is a hallmark of HPV-mediated cervical cancer; Matrix metalloproteinase [MMP]-2 and tissue inhibitor of metalloproteinase [TIMP]-2 are emerging as pivotal players in inflammation and carcinogenesis. My study aimed to evaluate the role of MMP-2 (-735C>T) [rs2285053] and TIMP-2 (-418G>C) [rs8179090] gene polymorphisms in HPV-mediated cervical cancer susceptibility in North Indian women.
Methods: Hospital-based case-control epidemiology study in Lucknow, Uttar Pradesh, India; power-analysis sample size was calculated by Quanto-software (version1.0) (http://hydra.usc.edu/gxe) with input of variables: significance-level (α)<0.05 (2-sided), model-of-inheritance:log additive, allele frequency lowest in controls, genetic effect for Odds Ratio (OR)≥1.65 yielding >80% statistical power: N=400 study subjects viz. 200 histopathologically confirmed cervical cancer cases and 200 healthy controls: age-matched and similar ethnicity i.e. North Indian. Genomic DNA extraction from peripheral blood samples collected from study-subjects was carried out using salting-out method. MMP-2 and TIMP-2 genotyping was performed using polymerase chain reaction-based restriction fragment length polymorphism. χ2 goodness-of-fit test was used for any deviation from Hardy-Weinberg equilibrium in controls; chi-square analysis was utilized to determine differences in genotype and allele frequencies. Binary logistic regression was applied to estimate age-adjusted Odds Ratio (OR) with Bonferroni’s correction for multiple comparisons.
Results and Conclusions: My findings demonstrated no significant association between MMP-2(-735C>T) and TIMP-2 (-418G>C) gene polymorphisms and risk of developing cervical cancer in the study-population. Interestingly, stratified-analysis using a case-only approach revealed no effect of MMP-2/TIMP-2 polymorphisms on early (FIGO I, II) and advanced stages (FIGO III, IV) of cervical cancer; MMP-2 and TIMP-2 polymorphisms did not modulate risk in cervical cancer patients who smoked tobacco/cigarettes. Overall, my innovative study demonstrated lack of association between MMP-2 and TIMP-2 gene polymorphisms and cervical cancer susceptibility in women of North Indian ethnicity; HPV-genotyping suggested that higher the viral load in terms of test cut-off value, higher was susceptibility to develop cervical cancer.
