hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer

Background: The aim of this study was to search for mutations in the human mutS homolog 2 (hMSH2) and human mutL homolog I (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nompolyposis colorectal cancer (HNPCC). Methods: The families were grouped according to the following clinical criteria: Amsterdam I or 11; familial colorectal cancer (CRC); an early age of onset of CRC in the proband only; or with at least one or two relatives who had HNPCC-related cancers; CRC in the proband only. All patients were studied with direct sequencing. Results: Ten mutations Were detected (10 of 25 [40%]); of nine different mutations, seven were novel. The hMLH1 gene had a higher mutation detection rate than hMSH2 (8 of 25 [32%] vs. 2 of 25 [8%]). Only 3 of these 10 families fulfilled the Amsterdam criteria. Two different polymorphisms were detected in the hMLH1 gene and four in the hMSH2 gene. Conclusions: The hMLH1 gone had a higher mutation detection rate than hMSH2. The physician who deals with CRC must take into consideration the heredity issue with patients who present with an early age of onset or a familial history of CRC- or HNPCC-related cancers, including gastric cancer, even if they do not fulfill the former Amsterdam criteria.