Breast cancer risk assessment based on susceptibility genes and polygenic risk score in Vietnamese women.

Background: Breast screening recommendation based on individual risk assessment is emerging as an alternative approach to improve compliance and efficiency to detect breast cancer (BC) early. In Vietnam, prior knowledge to stratify risk based on genetic factors is currently lacking.

Methods: This study recruited 892 BC patients and 735 healthy Vietnamese women from 2016 to 2021. DNA from blood samples of BC patients was first analyzed for pathogenic variants associated with hereditary breast and ovarian cancer syndrome (HBOC). For patients with no HBOC and healthy participants, DNA was genotyped for 398 BC susceptibility single-nucleotide polymorphism (SNPs) by next-generation sequencing to identify significantly associated SNPs and construct a polygenic risk score (PRS).

Results: The prevalence of HBOC predisposition gene mutations in Vietnamese women with BC was 5.4%. HBOC cases were significantly younger and enriched in the age group of 20-39 years old. In patients with no HBOC, we found 36 SNPs significantly associated with BC that were mostly similar to other Asian ethnicities; 34 of them were used to build a PRS model achieving an area under the receiver operating characteristics curve of 0.61 (95% CI: 0.56-0.68). Women in the top 1% PRS percentile had an odds ratio of 5.09 (95% CI: 3.10-7.86) while those in the bottom 1% had an odds ratio of 0.21 (95% CI: 0.09-0.39) to develop BC.

Conclusions: This study provides the first large datasets for HBOC gene analysis, BC susceptibility SNP association testing, and PRS modeling for Vietnamese women. Together, these data could aid the development of personalized BC screening recommendations for women in Vietnam.