MLH1 Ile219Val polymorphism in argentinean families with suspected lynch syndrome

DOMINGUEZ-VALENTIN, MEV; WERNHOFF, PATRIK; CAJAL, ANDREA R.; KALFAYAN, PABLO G.; PIÏ¿½ERO, TAMARA A.; GONZALEZ, MARIA L.; FERRO, ALEJANDRA; SAMMARTINO, INES; CAUSADA CALO, NATALIA S.; VACCARO, CARLOS A.

Frontiers in Oncology

Frontiers Media S.A.

Año: 2016 vol. 6

In the current study, no association was observed between theMLH1 Ile219Val polymorphism and cancer risk. This is consistent with several functional analyses indicating that the variant hasbinding properties to PMS2 and DNA repair efficiency similarto the wild type (29, 30). A recent CRC meta-analysis including8068 cases and 6568 controls from Australia, Czech Republic,Spain, Germany, and Sweden with frequencies of 0.678 and0.671, respectively, found not associations of CRC risk and MLH1Ile219Val polymorphism (31). However, Kim et al. suggestedthat the homozygosity for the 219V variant was correlated witha significantly reduced MLH1 expression among sporadic CRCcases (32). The difference might be a reflection of environmentalimpact on gene distribution, ethnic background or small-sizedfamily cohort (33?35).We found that the absence of the MLH1 Ile219Val polymorphism was associated with an early mean age at CRC cancer diagnosis, and the development of breast tumors was the main clinical features. This is in line with the Brazilian hereditary non-polyposis colorectal cancer (HNPCC) familial study that reported that breast cancer followed by endometrial and uterine cervix cancer are the most frequent extracolonic tumors found in women (36). Although, this is a small increase in breast cancer risk, it might point out interesting biological connections.In summary, our findings point to a high frequency of theMLH1 Ile219Val polymorphism in the Argentinean familieswith suspected Lynch syndrome and its modifier effect withthe disease-predisposing MLH1/MSH2 genes mutations. Ourdata may provide important clues to contribute to moleculardiagnostics, improved risk stratification, and targeted therapeuticstrategies in hereditary CRC.