Replication of genome-wide discovered breast cancer risk loci in the Cypriot population
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Genome-wide association studies (GWAS) have identified associations with robust statistical support for influencing breast cancer susceptibility. Most GWAS and replications have been conducted in Northern European populations and to a lesser extent in Asians, and Ashkenazi Jews. It is important to evaluate whether these variants confer risk across different populations and also to assess the magnitude of risk conferred. The aim of this study was to evaluate previously GWAS-identified breast cancer risk variants in the Cypriot population. Eleven GWAS-discovered single nucleotide polymorphisms (SNPs) were analyzed for association with breast cancer in 1,109 Cypriot female breast cancer patients and 1,177 healthy female controls. Four of the 11 SNPs evaluated were found to be nominally significantly associated (P < 0.05) with breast cancer risk in the Cypriot population. Based on estimated power, five associations would be expected to be nominally significant. The correlation coefficient of effect sizes (per-allele odds ratio) between the Cypriot population and the original GWAS populations where these SNPs had been discovered was 0.58 (P = 0.064), while allele frequencies were very similar (r = 0.88, P < 0.001). Overall, we show modest concordance for breast cancer GWAS-discovered alleles and their effect sizes in the Cypriot population. The effects sizes of GWAS-discovered SNPs need to be verified separately in different populations.
KeywordsBreast cancer Cyprus GWAS replication SNP
The authors thank Drs Yiola Marcou, Eleni Kakouri, Maria Daniel, Panayiotis Papadopoulos, and Simon Malas for their assistance in recruiting breast cancer patients. The authors also thank Rena Papachristoforou and Thalia Michael for their assistance in data collection, and Christina Flouri and Ioanna Neophytou for help with genotyping. The authors are indebted to all study participants. This study is co-funded by the Republic of Cyprus through Cyprus Research Promotion Foundation, the European Union Regional Development Structural Funds (Grant:ΥΓΕΙΑ/ΒΙΟΣ/0308 (ΒΙΕ)/08) and the Cyprus Institute of Neurology and Genetics.
Conflict of interest
- 7.Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A et al (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130PubMedCrossRefGoogle Scholar
- 24.The International Hapmap Consortium (2003) The international hapmap project. Nature 426:789–796Google Scholar