Evaluating new candidate SNPs as low penetrance risk factors in sporadic breast cancer: a two-stage Spanish case-control study.

OBJECTIVES:A polygenic model has been proposed in order to explain the genetic susceptibility to sporadic breast cancer. According to this model, common population variants would be responsible for low to modest effects on the risk of developing the disease. We have carried out a high-throughput SNP genotyping project in order to shed some light on the complex genetic aetiology of non-familial breast cancer. METHODS:Ninety-one genes have been selected because of their implications in several candidate cell pathways for breast cancer. A total of 640 SNPs in these genes were genotyped in a series of 450 consecutive cases and 448 controls from mainland Spain. Promising SNPs were then studied in an independent series of 294 cases and 299 controls from the Canary Islands. RESULTS:In the first case-control series we identified 25 SNPs with P-values below 0.05 (under a 1 df Chi-square test), five of them with P-values below 0.01 (best=0.0008). In the stage 2 Canary Islands series, odd ratios (OR) for two SNPs in HUS1 were in a consistent direction. CONCLUSIONS:SNPs located at the gene HUS1 are good candidates for further investigation in independent association studies and functional assays.

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