Cost-utility analysis of genetic screening in families of patients with germline MUTYH mutations

Abstract

Background: MUTYH associated polyposis (MAP) is an autosomal recessive inherited disorder. Carriers of bi-allelic MUTYH germline mutations have a risk of approximately 60% to develop colorectal carcinoma (CRC). In the general population about 1.5% is a heterozygous MUTYH mutation carrier. Children of MAP patients have an increased risk of inheriting two MUTYH mutations compared to the general population, implicating an increased risk for developing CRC.

Screening for variants in the <i>MUTYH</i> gene in Saudis

“…Different variants of the MUTYH gene can affect the protein function and hence the DNA repair capacity that is tightly linked to cancer development. Biallelic germline mutations in the MUTYH lead to MUTYH associated polyposis (MAP) and provide a significant risk for colorectal cancer [24]. Different studies supported the role of MUTYH in colorectal adenoma and carcinoma pre-disposition [33,34].…”

“…Although carriers of biallelic MUTYH mutations have a 60% risk to develop CRC [24] it is now clear that some genes which cause autosomal recessive cancers predisposition are related to fairly increased risk of adult cancer in monoallelic carriers [25]. Such monoallelic mutations may be strongly related to cancer when combined with other genes mutations [26] or carcinogen exposure [27] and they also can influence genetic pathways in CRC [19].…”

Management of MUTYH‐associated neoplasia in Australia

“…One‐third of the respondents do not recommend regular upper gastrointestinal tract surveillance. The currently available evidence is insufficient to endorse or refute the recommendation, but the reported association of MAP with duodenal polyposis and other extracolonic features typical of FAP makes upper gastrointestinal surveillance not unreasonable, at least until more definitive data are available 11,19 …”

Gastrointestinal polyposis syndromes for the general gastroenterologist

“…Studies have shown biallelic MUTYH mutations in 26% to 29% of patients with 10–100 polyps,7 and in these families it is cost effective to perform genetic screening, since 2% of the normal population is heterozygous for an MUTYH mutation; a child of a biallelic mutation carrier has a 1% chance of inheriting two mutated MUTYH alleles 15. However, the true prevalence of MAP remains unclear, and the phenotypic characteristics are still being determined.…”