Single nucleotide polymorphisms in the 20q13 amplicon genes in relation to breast cancer risk and clinical outcome

The 20q13 region is frequently amplified/overexpressed in breast tumours. However, the nature of this amplification/overexpression is unknown. Here, we investigated genetic variation in five 20q13 amplicon genes (MYBL2, AURKA, ZNF217, STK4 and PTPN1) and its impact on breast cancer (BC) susceptibility and clinical outcome. As a novel finding, four polymorphisms in STK4 (rs6017452, rs7271519) and AURKA (rs2273535, rs8173) associated with steroid hormone receptor status both in a Swedish population-based cohort of 783 BC cases and in a Polish familial/early onset cohort of 506 BC cases. In the joint analysis, the minor allele carriers of rs6017452 had more often hormone receptor positive tumours (OR 0.57, 95% CI 0.40–0.81), while homozygotes for the minor allele of rs7271519, rs2273535 and rs8173 had more often hormone receptor negative tumours (2.26, 1.30–3.39; 2.39, 1.14–5.01; 2.39, 1.19–4.80, respectively) than homozygotes for the common allele. BC-specific survival analysis of AURKA suggested that the Swedish carriers of the minor allele of rs16979877, rs2273535 and rs8173 might have a worse survival compared with the major homozygotes. The survival probabilities associated with the AURKA genotypes depended on the tumour phenotype. In the Swedish case–control study, associations with BC susceptibility were observed in a dominant model for three MYBL2 promoter polymorphisms (rs619289, P = 0.02; rs826943,P = 0.03 and rs826944, P = 0.02), two AURKA promoter polymorphisms (rs6064389, P = 0.04 and rs16979877, P = 0.02) and one 30UTR polymorphism in ZNF217 (rs1056948, P = 0.01). In conclusion, our data confirmed the impact of the previously identified susceptibility locus and provided preliminary evidence for novel susceptibility variants in BC. We provided evidence for the first time that genetic variants at 20q13 may affect hormone receptor status in breast tumours and influence tumour aggressiveness and survival of the patients. Future studies are needed to confirm the prognostic value of our findings in the clinic