Case-Control Study for 23 Cancer Types With Functional Analysis of : Risk Estimation and Clinical Recommendations in East Asia.

Purpose: is the frequently detected cancer-predisposing gene in female breast cancer. In addition, the association with the risks of other cancer types has been suggested, and clinical management has also been discussed. Although clinical relevance of germline variants differs across population, there is little evidence of the clinical relevance of germline variants in East Asia.

Methods: Targeted sequencing and functional analyses of missense variants for the coding region of in 111,571 East Asian individuals were performed. Variants classified as pathogenic/likely pathogenic in ClinVar, predicted loss-of-function, or functionally impaired in functional analysis were defined as germline damaging variants (gDVs). We evaluated the association between gDVs and the risk of 23 cancer types. We also compared the clinical characteristics of carriers and noncarriers among patients with -associated cancers.

Results: We identified 77 gDVs including 36 functionally impaired missense variants. gDVs were significantly associated exclusively with prostate cancer (odds ratio [OR], 1.8 [95% CI, 1.2 to 2.6]; 1.7 × 10), in addition to female breast cancer (OR, 1.8 [95% CI, 1.3 to 2.6]; 1.2 × 10), among 23 cancer types. There were no differences in age at diagnosis, pathologic status, and prognosis between carriers and noncarriers. Besides, there was no association with the risk of cancer types with high incidence rates in East Asian countries.

Conclusion: gDVs were associated with female breast and prostate cancer risks in East Asia. The necessity of additional systematic clinical management for all gDV carriers should be carefully discussed, and standard cancer screening is recommended unless no other clinical features suggestive of cancer predisposition are noted in East Asia.