Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas.
Biallelic germline mutations of MUTYH have been shown to predict familial and sporadic multiple colorectal adenomas and carcinomas, however, whether there is an association between single nucleotide polymorphisms (SNPs) of MUTYH and sporadic colorectal cancer (CRC) risk has remained unclear.
Recently, it has been shown that germline mutations in MUTYH predispose to MUTYH-associated polyposis (MAP), an autosomal recessive disorder characterised by multiple colorectal adenomas and carcinomas.
Three SNPS modified the effect of smoking (MUTYH interaction p = 0.002; OGG1 interaction p = 0.013); FEN1 interaction p = 0.013)), one SNP in LIG3 modified the effect of alcohol consumption (interaction p = 0.024) and two SNPs in LIG3 modified the effect of dietary folate (interaction p = 0.001 and p = 0.08) on colorectal adenoma risk.
Our data suggest that the contribution of bi-allelic MUTYH mutations to the development of CRC in Dutch non-polyposis patients that meet clinical genetic referral criteria, and to the development of low number of colorectal adenomas in non-CRC patients, is likely to be low.
MAP (MutYH-associated polyposis) is a recently described colorectal adenoma and carcinoma predisposition syndrome that is associated with biallelic-inherited mutations of the human MutY homologue gene, MutYH.MutYH is often also termed MYH.
Biallelic inherited mutations in the oxidative DNA damage repair gene MUTYH predispose to colorectal adenomas and colorectal carcinoma (CRC) with high penetrance.
In this study, screening for germinal mutations in the MYH gene was performed in 53 Portuguese individuals with multiple colorectal adenomas or classic adenomatous polyposis, in whom no mutation had been identified in the APC gene.
The MUTYH gene encodes a DNA glycosylase that can initiate the excision repair of adenine mispaired with 8-hydroxyguanine (8OHG) and is responsible for a susceptibility to multiple colorectal adenomas and carcinomas.
Recessively inherited mutations in the base excision repair gene MYH have recently been associated with predisposition to colorectal adenomas and cancer in materials selected for occurrence of multiple adenomas.
Recessively inherited mutations in the base excision repair gene MYH have recently been associated with predisposition to colorectal adenomas and cancer.
The expression of MUTYH protein in colorectal adenomas or cancer was studied by IHC using three different (1 polyclonal and 2 monoclonal) antibodies in six samples from patients with biallelic MUTYH mutations, in three samples from patients with a single MUTYH mutation, and in 11 samples from patients without MUTYH mutations.
To determine the prevalence of pathogenic APC and MUTYH mutations in patients with multiple colorectal adenomas who had undergone genetic testing and to compare the prevalence and clinical characteristics of APC and MUTYH mutation carriers.
Very recently, germline mutations in the base-excision repair gene MYH have been associated with recessive inheritance of multiple colorectal adenomas in a subset of patients.
However, limited data are available on the duodenal phenotype of patients with multiple colorectal adenomas (10-99) without a germline APC or MUTYH mutation.