Carrier Frequency and Incidence of -Associated Polyposis Based on Database Analysis in East Asians and Koreans.

BACKGROUND

-associated polyposis is an autosomal recessive disorder associated with an increased lifetime risk of colorectal cancer and a moderately increased risk of ovarian, bladder, breast, and endometrial cancers. We analyzed the carrier frequency and estimated the incidence of -associated polyposis in East Asian and Korean populations, for which limited data were previously available.

METHODS

We examined 125,748 exomes from the gnomAD database, including 9,197 East Asians, and additional data from 5,305 individuals in the Korean Variant Archive and 1,722 in the Korean Reference Genome Database. All variants were interpreted according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines and the Sequence Variant Interpretation guidelines from ClinGen.

RESULTS

The global carrier frequency of -associated polyposis was 1.29%, with Europeans (non-Finnish) having the highest frequency of 1.86% and Ashkenazi Jews the lowest at 0.06%. East Asians and Koreans had a carrier frequency of 0.35% and 0.37% and an estimated incidence of 1 in 330,409 and 1 in 293,304 in Koreans, respectively, which were substantially lower than the global average of 1 in 24,160 and the European (non-Finnish) incidence of 1 in 11,520.

CONCLUSIONS

This was the first study to investigate the frequency of carriers of -associated polyposis in East Asians, including specific subgroups, utilizing gnomAD and a Korean genome database. Our data provide valuable reference information for future investigations of -associated polyposis to understand the genetic diversity and specific variants associated with this condition in East Asian populations.