Lack of associations of the COMT Val158Met polymorphism with risk of endometrial and ovarian cancer: a pooled analysis of case-control studies.

Jin-Xin Liu,Xia Li,Da-Peng Ding,Rong-Cheng Luo,Rong Li,Yu-Wu Guo,Yi-Zhi Chen

doi:10.7314/apjcp.2014.15.15.6181

Abstract

This meta-analysis was conducted to examine whether the genotype status of Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with endometrial and ovarian cancer risk. Eligible studies were identified by searching several databases for relevant reports published before January 1, 2014. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. In total, 15 studies (1,293 cases and 2,647 controls for ovarian cancer and 2,174 cases and 2,699 controls for endometrial cancer) were included in the present meta-analysis. When all studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val158Met polymorphism and ovarian cancer risk (Val/Met versus Val/Val: OR=0.91, 95% CI=0.76-1.08; Met/Met versus Val/Val: OR=0.90, 95% CI=0.73-1.10; dominant model: OR=0.90, 95% CI=0.77-1.06; recessive model: OR=0.95, 95% CI=0.80-1.13). Similarly, no associations were found in all comparisons for endometrial cancer (Val/Met versus Val/Val: OR 0.97, 95% CI=0.77-1.21; Met/Met versus Val/Val: OR=1.02, 95% CI=0.73-1.42; dominant model: OR=0.98, 95% CI=0.77-1.25; recessive model: OR=1.02, 95% CI=0.87-1.20). In the subgroup analyses by source of control and ethnicity, no significant associations were found in any subgroup of population. This meta-analysis strongly suggests that COMT Val158Met polymorphism is not associated with increased endometrial and ovarian cancer risk.

Highlights

Ovarian cancer is associated with the highest mortality rate among gynaecological malignancies (Hennessy et al, 2009)
When all studies were pooled into the meta-analysis, there was no evidence for significant association between COMT Val158Met polymorphism and ovarian cancer risk (Val/Met versus Val/Val: odds ratios (ORs)=0.91, 95% confidence interval (CI)=0.76-1.08; Met/Met versus Val/Val: OR=0.90, 95% CI=0.73-1.10; dominant model: OR=0.90, 95% CI=0.77-1.06; recessive model: OR=0.95, 95% CI=0.80-1.13)
Eligible Studies and Meta-analysis Databases A total of 15 studies with full-text articles examined the association of COMT Val158Met polymorphism with endometrial and ovarian cancer were found

Summary

Introduction

Ovarian cancer is associated with the highest mortality rate among gynaecological malignancies (Hennessy et al, 2009). Multiple lines of evidence support a central role of hormones in the etiology of endometrial and ovarian cancers (Lundin et al, 2012). Polymorphisms within genes responsible for estrogen catabolism could alter cellular levels of genotoxic 4-hydroxylated catechol estrogens and antiangiogenic 2-methoxyestradiol, influencing risk of developing endometrial and ovarian cancers. Lachman et al identified a functional polymorphism in the COMT gene, a G-A transition at codon 158 in exon 4, leading to a substitution of methionine for valine that result in a thermolabile enzyme with reduced activity (Lachman et al, 1996). It has been hypothesized that this COMT polymorphism (rs4680) may modulate risk of hormonally responsive cancers because of a decreased ability of COMT to methylate and thereby inactivate catechol estrogens, as well as through decreased production of the intermediate products of catechol estrogen metabolism (Lajin et al, 2013)

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