There is limited data on the efficacy of surveillance in prevention of CRC development in MUTYH biallelic carriers.
The majority of, but not all, patients with biallelic MUTYH gene pathogenic variants and CRC have polyps at presentation. The polyps include adenomas and serrated polyps. The risk of CRC does not appear to correlate with the number of polyps.r 29% of population-based biallelic MUTYH patients with CRC do not have co-existing adenomas.r Thus, colonoscopy surveillance is suggested for patients with biallelic MUTYH pathogenic variants independent of the presence of polyps.
The mean age of diagnosis of CRC in patients with biallelic MUTYH gene pathogenic variants is age 48-53 years.rr In one study the risk of developing a primary or metachronous CRC within 5 years of follow-up was approximately 10%.r The high risk of CRC development in patients under surveillance suggests an accelerated carcinogenesis mechanism. Thus, regular colonoscopies are proposed.r Subtotal colectomy with rectum sparing may be appropriate in the absence of rectal cancer or rectal polyposis with regular ongoing surveillance of the rectal stump.r
A genotype-phenotype correlation has been reported for Y165C homozygotes being at increased risk for CRC.r
Duodenal polyposis and cancer
There are no studies to show the efficacy of gastrointestinal endoscopy in reducing the risk for duodenal cancer in MAP. There is an increased risk for duodenal polyps and cancer and surveillance has been recommended on the basis of the similarities of the MAP phenotype and attenuated FAP, though the age of presentation is older and frequency of polyposis is less in the MAP phenotype.rr A recent study has suggested that surveillance chromoendoscopy enhances the detection rate of duodenal adenomas and there is a significant increase in the Spiegelman stage based on the numbers of polyps.r
A genotype-phenotype correlation has been reported for Y165C homozygotes being at increased risk for duodenal polyps and cancer.r
Extraintestinal cancers have been described in patients with biallelic MUTYH gene pathogenic variants,r but whether they are causally linked is debated. No specific surveillance is recommended for these. Cutaneous manifestations include sebaceous gland tumours, lipomas and malignant skin cancers. The data is not sufficient to determine the prevalence.
Increased risk of other cancer types has been suggested (including cancer of the ovary, bladder, breast and endometrium) but more research is required as data is conflicting. Screening and advice should be based on the family history of these cancers.r