The methods described herein have not only been leveraged to provide insight into the roles of the MutY Fe-S cluster but have also been provided crucial information needed to delineate the impact of inherited variants of the human homolog MUTYH associated with a colorectal cancer syndrome known as MUTYH-associated polyposis or MAP.
The base excision repair gene MUTYH is the causative gene of colorectal polyposis syndrome, which is an autosomal recessive disorder associated with a high risk of colorectal cancer.
In addition to the well-established role of the DNA glycosylase gene MUTYH, biallelic mutations in which predispose to MUTYH-associated polyposis, a second DNA glycosylase gene, NTHL1, has recently been associated with adenomatous polyposis and a high colorectal cancer risk.
The paramount role of MUTYH in guarding the genome is well established in the etiology of a colorectal cancer predisposition syndrome involving variants of MUTYH, referred to as MUTYH-associated polyposis (MAP).
MYH-associated polyposis is a recessively inherited syndrome of colorectal cancer predisposition attributed to biallelic germline mutations in the base excision repair gene MYH.
To uncover novel causative genes in patients with unexplained adenomatous polyposis, a model disease for colorectal cancer, we performed a genome-wide analysis of germline copy number variants (CNV) in a large, well characterized APC and MUTYH mutation negative patient cohort followed by a targeted next generation sequencing (NGS) approach.
Within the limited power of this study, there was no evidence that a monoallelic MUTYH gene mutation confers additional risk of colorectal cancer for carriers of a MMR gene mutation alone.
The second cohort contained 921 patients with colorectal cancer <50 years and <10 reported colorectal adenomas who had undergone MUTYH mutation testing.
Germline mutations in the MUTYH gene are linked to colorectal polyposis and a high risk of colorectal cancer, a syndrome referred to as MUTYH-associated polyposis (MAP).
Profuse gastrointestinal polyposis is associated with rare, inherited colorectal cancer predisposition syndromes, most commonly caused by mutations in the adenomatous polyposis coli (APC) or mutY homolog (MUTYH) genes.
Germline and somatic mutations in BER genes, such as MutY Homolog (MUTYH/MYH) and DNA-directed polymerase (POLB), are associated with increased risk of colorectal cancer.
Biallelic mutations in the MYH gene have been shown to increase the risk of colorectal cancer over the lifetime of the mutation carrier.1,2 However, there is no clear consensus in the literature as whether a monoallelic mutation increases the risk for colorectal cancer.3 In this report, we postulate that a single mutation is sufficient to increase the risk of colorectal cancer.
MUTYH germline mutations cause an inherited polyposis, MUTYH-associated-polyposis, characterized by multiple adenomas and increased susceptibility to colorectal cancer.
Contribution of bi-allelic germline MUTYH mutations to early-onset and familial colorectal cancer and to low number of adenomatous polyps: case-series and literature review.
The results obtained in our study indicated an association of OGG1 and MUTYH genes polymorphisms involved in oxidative DNA lesions repair with the risk occurrence of colorectal cancer in Polish patients.