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Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas
Author(s) -
Gismondi Viviana,
Meta Maurizio,
Bonelli Luigina,
Radice Paolo,
Sala Paola,
Bertario Lucio,
Viel Alessandra,
Fornasarig Mara,
Arrigoni Arrigo,
Gentile Mattia,
Ponz de Leon Maurizio,
Anselmi Luca,
Mareni Cristina,
Bruzzi Paolo,
Varesco Liliana
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20054
Subject(s) - mutyh , germline mutation , germline , adenoma , adenomatous polyposis coli , population , colorectal cancer , biology , colorectal adenoma , genetics , medicine , mutation , cancer research , gastroenterology , gene , cancer , environmental health
Biallelic germline mutations in the base excision repair gene MYH have been reported in patients with multiple colorectal adenomas and cancer and in sporadic FAP patients not showing a detectable APC germline mutation. In this study, the prevalence of the common Y165C and G382D germline variants of the MYH gene was examined in 70 FAP/AAPC patients with no detectable APC mutation and a family history compatible with recessive inheritance. In addition, 141 normal‐population adenoma patients (mean number of adenomas, 2.8; range, 1–9) and 52 clean colon controls were studied. The entire coding region of the MYH gene was analyzed in Y165C or G382D heterozygous patients. Since the same second mutational event (a 3 bp deletion in exon 14, 1395delGGA) was detected in 3 patients, the prevalence of this variant was also examined in all groups. In all, 14 of 70 patients in the FAP/AAPC group (20%; 95% CI = 11.7–31.6%) had biallelic germline MYH variants and 3 were heterozygotes (4.3%). None of the 141 normal‐population adenoma patients carried biallelic germline MYH variants (95% CI = 0.06–4.1%) and 3 were heterozygotes (2.1%). In the control group, no MYH variants were detected. These results indicated that MYH ‐associated polyposis (MAP) is present in about 20% of Italian FAP/AAPC patients, in whom no germline APC mutation is detectable and showing a family history compatible with recessive inheritance, and in a small fraction of patients with colorectal adenomas in the general population. In addition, our data suggest that mutation 1395delGGA is a subpolymorphic MYH mutational event in some Caucasian populations. © 2004 Wiley‐Liss, Inc.