Here, we report the identification of seven further unrelated patients with >100 colorectal adenomas (six with colorectal cancer) and biallelic germline mutations in MYH: four were homozygous for truncating mutations, two were homozygous for Y165C and one was a Y165C/G382D compound heterozygote.
However, it was recently discovered that biallelic mutations in the BER DNA glycosylase MYH lead to an autosomal recessive syndrome of adenomatous colorectal polyposis and very high colorectal cancer risk.
These results confirm that biallelic MYH mutations confer susceptibility to colorectal cancer but are unlikely to account for more than 3% of early-onset colorectal cancer.
The aim of this study was to analyse the incidence of germ-line MYH mutations in selected Portuguese families recorded in a hereditary tumour registry and to evaluate the risk of colorectal cancer in this syndrome.
We show that biallelic MUTYH defects impart a 93-fold (95% CI 42-213) excess risk of colorectal cancer, which accounts for 0.8% of cases aged <55 years and 0.54% of the entire cohort.
Biallelic germline mutations of MUTYH-a gene encoding a base excision repair protein-are associated with an increased susceptibility of colorectal cancer.
AXIN2 and MUTYH genes were screened for germline mutations by PCR and direct sequencing in 39 unrelated patients with multiple adenomas or colorectal cancer without evidence of APC mutation nor mismatch repair defect.
In summary, biallelic germline mutations of MYH are unlikely to cause colorectal cancer in patients sharing clinical features with hereditary nonpolyposis colorectal cancer families without mismatch repair defect and therefore cannot fill the molecular diagnostic gap in this subgroup of Bethesda-positive patients.
The examined MYH-mutation positive patients were found to have higher risks of colorectal cancer at diagnosis, right-sided location of cancers, and a significantly lower incidence of upper gastrointestinal manifestations, compared with APC-mutation positive patients.
Multiplex tetra-primer amplification refractory mutation system PCR to detect 6 common germline mutations of the MUTYH gene associated with polyposis and colorectal cancer.
A single patient with an inherited MYH mutation as well as a subset of 26 patients presenting with a family history of colorectal cancer were screened for additional MYH mutations by direct sequencing of the entire coding region.
We observed a nonstatistically significant association between these MUTYH mutations at a heterozygous state and an increase in colorectal cancer risk (odds ratio [OR] 1.26, 95% confidence interval [CI] 0.70-2.27).
The importance of preventing mutations associated with 8-oxoguanine is shown by a direct association between defects in the DNA glycosylase MUTYH and colorectal cancer.
Germ-line predisposition to colorectal cancer was identified in 37 probands [3.4%; 95% confidence interval (95% CI), 2.4-4.6]: 29 with MLH1/MSH2 mutations, 2 with familial adenomatous polyposis, 1 with juvenile polyposis, and 5 with biallelic MYH variants.
The value of MUTYH testing in patients with early onset microsatellite stable colorectal cancer referred for hereditary nonpolyposis colon cancer syndrome testing.
The joint effect of tobacco exposure and the MUTYHGln324His showed a significant association with colorectal cancer risk in non-smokers (adjusted OR 4.08, 95%CI 1.22-13.58, p = 0.022) and the APEX1 Asp148Glu was significantly increased in smokers (adjusted OR 5.02, 95%CI 1.80-13.99, p = 0.002).