hMLH1 andhMSH2 gene mutation in Brazilian families with suspected hereditary nonpolyposis colorectal cancer

• DOI: 10.1007/bf02573891
• Publication Date: 2007-03-22T14:21:15Z
• Authors: Benedito Mauro Rossi; Ademar Lopes; Fabio Oliveira Fe...; Wilson Toshihiko ...; Cláudia C. Napoli...; José C. Casali da...; Catarina C. Simpson; Andrew J. G. Simpson
• Keywords: Adult; Male; Polymorphism, Genetic; Adolescent; Nuclear Proteins; Middle Aged; Colorectal Neoplasms, Hereditary Nonpolyposis; Neoplasm Proteins; Pedigree; 3. Good health; DNA-Binding Proteins; 03 medical and health sciences; MutS Homolog 2 Protein; 0302 clinical medicine; Proto-Oncogene Proteins; Mutation; Humans; Female; Carrier Proteins; MutL Protein Homolog 1; Brazil; Adaptor Proteins, Signal Transducing; Aged

The aim of this study was to search for mutations in the human mutS homolog 2 (hMSH2) and human mutL homolog 1 (hMLH1) genes in 25 unrelated Brazilian kindreds with suspected hereditary nonpolyposis colorectal cancer (HNPCC).The families were grouped according to the following clinical criteria: Amsterdam I or II; 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.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.The hMLH1 gene 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.