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Analysis of inherited MYH/(MutYH) mutations in British Asian patients with colorectal cancer

Biallelic inherited mutations of the MYH gene (also known as MutYH or human MutY homologue) are associated with multiple colorectal adenomas and a high risk of colorectal cancer that approaches 100%.1,2 This recessive disorder has become known as MYH-associated polyposis (MAP) to distinguish it from dominantly inherited familial adenomatous polyposis. The risk of colorectal cancer in heterozygotes seems to be only marginally increased, if at all.2 During a review of the Wales Polyposis Register we noted that although only 4 of the 115 recorded families were of Asian origin, all four had MAP. This was in contrast to the 111 indigenous families, only 12 of which had MAP. All affected members of three unrelated British Indian families were homozygous for the mutation E466X and one patient of Pakistani descent was homozygous for Y90X.3 These mutations have not been observed in other ethnic groups. As the overall incidence of colorectal cancer among Asians living in England and Wales is markedly below that of the general population,4 we postulated that MYH mutations might contribute more significantly to colorectal cancer among British Asians than among indigenous northern Europeans. We conducted a retrospective study to assess the contribution of MYH mutations to colorectal cancer among British Asians.