Evaluation of three polygenic risk score models for the prediction of breast cancer risk in Singapore Chinese.

Autor:	Chan CHT; Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore., Munusamy P; Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore., Loke SY; Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore., Koh GL; Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore., Yang AZY; Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore., Law HY; DNA Diagnostic and Research Laboratory, KK Women's and Children's Hospital, Singapore., Yoon CS; DNA Diagnostic and Research Laboratory, KK Women's and Children's Hospital, Singapore., Wong CY; Department of General Surgery, Singapore General Hospital, Singapore., Yong WS; Department of Surgical Oncology, National Cancer Centre, Singapore., Wong NS; Department of Medical Oncology, National Cancer Centre, Singapore.; Oncocare Cancer Centre, Gleneagles Medical Centre, Singapore., Ng RCH; Department of Medical Oncology, National Cancer Centre, Singapore., Ong KW; Department of Surgical Oncology, National Cancer Centre, Singapore., Madhukumar P; Department of Surgical Oncology, National Cancer Centre, Singapore., Oey CL; Department of Surgical Oncology, National Cancer Centre, Singapore., Ho GH; Department of Surgical Oncology, National Cancer Centre, Singapore.; Koong and Ho Surgery Centre, Singapore., Tan PH; Department of Pathology, Singapore General Hospital, Singapore., Tan MH; Department of Medical Oncology, National Cancer Centre, Singapore.; Institute of Bioengineering and Nanotechnology, Singapore.; Lucence Diagnostics Pte Ltd, Singapore., Ang P; Department of Medical Oncology, National Cancer Centre, Singapore.; Oncocare Cancer Centre, Gleneagles Medical Centre, Singapore., Yap YS; Department of Medical Oncology, National Cancer Centre, Singapore., Lee ASG; Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore.; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.; Office of Clinical and Academic Faculty Affairs, Duke-NUS Graduate Medical School, Singapore.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 Jan 31; Vol. 9 (16), pp. 12796-12804. Date of Electronic Publication: 2018 Jan 31 (Print Publication: 2018).
DOI:	10.18632/oncotarget.24374
Abstrakt:	Genome-wide association studies (GWAS) have proven highly successful in identifying single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. The majority of these studies are on European populations, with limited SNP association data in other populations. We genotyped 51 GWAS-identified SNPs in two independent cohorts of Singaporean Chinese. Cohort 1 comprised 1294 BC cases and 885 controls and was used to determine odds ratios (ORs); Cohort 2 had 301 BC cases and 243 controls for deriving polygenic risk scores (PRS). After age-adjustment, 11 SNPs were found to be significantly associated with BC risk. Five SNPs were present in <1% of Cohort 1 and were excluded from further PRS analysis. To assess the cumulative effect of the remaining 46 SNPs on BC risk, we generated three PRS models: Model-1 included 46 SNPs; Model-2 included 11 statistically significant SNPs; and Model-3 included the SNPs in Model-2 but excluded SNPs that were in strong linkage disequilibrium with the others. Across Models-1, -2 and -3, women in the highest PRS quartile had the greatest ORs of 1.894 (95% CI = 1.157-3.100), 2.013 (95% CI = 1.227-3.302) and 1.751 (95% CI = 1.073-2.856) respectively, suggesting a direct correlation between PRS and BC risk. Given the potential of PRS in BC risk stratification, our findings suggest the need to tailor the selection of SNPs to be included in an ethnic-specific PRS model. Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interests.
Databáze:	MEDLINE
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