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.
These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19∗ and p.Arg109TrpMUTYH variants are associated with functional impairments.
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 p.(Tyr179Cys)MUTYH germline mutations were found in one patient (frequency 1.18%) with CRC, urothelial carcinoma and a sebaceous gland carcinoma.
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.
Colorectal adenomatous polyposis is associated with a high risk of colorectal cancer (CRC) and is frequently caused by germline mutations in APC or MUTYH.
A recently described biallelic mutation of MYH, is responsible for adenomatous polyposis with an increased risk of CRC and is responsible for 30-40 % of adenomatous polyposis cases in which an APC mutation cannot be found.
Risks of CRC for carriers of monoallelic mutations in MUTYH with a first-degree relative with CRC are sufficiently high to warrant more intensive screening than for the general population.
Cumulative epidemiological evidence for a significant association with CRC risk was graded strong for eight variants in five genes (adenomatous polyposis coli (APC), CHEK2, DNMT3B, MLH1 and MUTYH), moderate for two variants in two genes (GSTM1 and TERT), and weak for 52 variants in 45 genes.
Age, sex, family history of CRC (APC/MYH), proximal/mixed/distal phenotype, indication for colonoscopy, number, size, location of the hyperplastic polyps, presence of mixed/adenomatous polyps, CRCI, follow-up and endoscopio/surgical treatment.
MUTYH germline mutations cause an inherited polyposis, MUTYH-associated-polyposis, characterized by multiple adenomas and increased susceptibility to colorectal cancer.
Biallelic inherited mutations in the oxidative DNA damage repair gene MUTYH predispose to colorectal adenomas and colorectal carcinoma (CRC) with high penetrance.
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.
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.
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.
Five monoallelic single nucleotide polymorphisms (SNPs) were identified in the 7 exon regions of MYH, which were detected in 75 (18.75%) of 400 CRC patients as well as 42 (7%) of 600 normal controls.
Several genetically defined hereditary colorectal cancer (CRC) syndromes are associated with colonic polyposis including familial adenomatous polyposis (FAP) and MUTYH adenomatous polyposis (MAP).
Clinical and molecular detection of inherited colorectal cancers in northeast Italy: a first prospective study of incidence of Lynch syndrome and MUTYH-related colorectal cancer in Italy.
Variants of the mutY homolog gene MutYH, a DNA repair gene, are associated with increased risk of colorectal cancer; however, it remains unclear whether these variants also are associated with the risk of other cancers.