Given that these tumor features are associated with the response to immune checkpoint inhibitors, we administered nivolumab to a CRC patient who carried two inactive MUTYH alleles (p.Y179C and p.G396D) and previously experienced failure of chemotherapy.
Given that these tumor features are associated with the response to immune checkpoint inhibitors, we administered nivolumab to a CRC patient who carried two inactive MUTYH alleles (p.Y179C and p.G396D) and previously experienced failure of chemotherapy.
Biallelic p.(Tyr179Cys) MUTYH germline mutations were found in one patient (frequency 1.18%) with CRC, urothelial carcinoma and a sebaceous gland carcinoma.
Homozygote carriers of G396D had nonsignificantly elevated risk of CRC (OR = 11.0, 95% CI: 0.91-213.9, p = 0.06), and combined bi-allelic carriers of G396D and Y179C had increased risk, OR = 17.4, 95% CI = (1.9-316.7, p = 0.009).
Homozygote carriers of G396D had nonsignificantly elevated risk of CRC (OR = 11.0, 95% CI: 0.91-213.9, p = 0.06), and combined bi-allelic carriers of G396D and Y179C had increased risk, OR = 17.4, 95% CI = (1.9-316.7, p = 0.009).
Fourteen years of colonoscopic surveillance of an MAP patient (compound heterozygous p.Y165C/p.G382D) showed that adenoma development was slow after initial diagnosis of a single colorectal carcinoma at the age of 44, but then the annual number of new adenomas increased substantially in the patient's early fifties.
The mean ages of CRC diagnosis in patients were 58 years (homozygous G396D) and 52 years (compound heterozygous G396D/Y179C) versus 46 years (homozygous Y179C; P = .001, linear regression).
The mean ages of CRC diagnosis in patients were 58 years (homozygous G396D) and 52 years (compound heterozygous G396D/Y179C) versus 46 years (homozygous Y179C; P = .001, linear regression).
The mean ages of CRC diagnosis in patients were 58 years (homozygous G396D) and 52 years (compound heterozygous G396D/Y179C) versus 46 years (homozygous Y179C; P = .001, linear regression).
Adenine removal activity and bacterial complementation with the human MutY homologue (MUTYH) and Y165C, G382D, P391L and Q324R variants associated with colorectal cancer.
The association of the p.Tyr165Cys mutation with fCRC indicates that this variant represents a susceptibility factor in a defined subgroup of CRC patients with a positive family history.
Using Fisher's exact test and logistic regression, we compared the frequency of the known disease-causing MYH mutations Y165C, G382D and 466delE in 137 probands (117 cases with CRC and 20 cases diagnosed on the basis of adenomatous polyps only) from families with three or more CRCs but negative for mutations in the MMR genes and in 967 healthy controls with comparable ethnic backgrounds.