RESEARCH COMMUNICATION MLH1 Polymorphisms and Cancer risk: a Meta-analysis Based on 33 Case-control Studies

Exogenous carcinogens and endogenous oxygen species can induce DNA damage and genomic instability that may lead to carcinogenesis (Barnes, 2002). In humans, there are several major DNA repair pathways which are expected to play a role in maintaining genomic stability (Bernstein et al., 2002), including nucleotide excision repair (NER), base excision repair (BER) and DNA double strand breaks (DSBs). The mismatch repair (MMR) pathway, first described in bacteria, is a highly conserved process which is responsible for recognizing and correcting DNA base pairing errors in newly replicated DNA (Harfe and Jinks-Robertson, 2000). It has been confirmed that double-strand break repair is also modulated by MMR (Jacob and Praz, 2002). MMR defective cell lines display various forms of genomic instability (Surtees et al., 2004). Animal experiments in mice indicate that MMR gene deficiencies lead to an increased level of microsatellite instability (MSI) and susceptibility to cancer (Ellison et al., 2004). In humans, loss of MMR function has been implicated in several