Analysis of common germline polymorphisms as prognostic factors in patients with lymph node-positive breast cancer

Abstract

Women with breast cancer that initially involves local lymph nodes have a higher risk for local recurrence or developing metastases. Recent data suggest that germline polymorphism is a significant, previously unrecognized factor in breast cancer progression and metastasis. We assessed the influence of 16 selected common germline polymorphisms in disease-free survival and overall survival among 216 women diagnosed with lymph node-positive breast cancer. The rare allele of FAS 1377G>A was significantly associated with prolonged disease-free survival (P = 0.012, risk ratio of recurrence (RR) = 0.557, 95% confidence interval (CI) = 0.353-0.878) in univariate analysis. After adjusting for known breast cancer prognostic factors the association remained significant (P = 0.050, RR = 0.500, CI = 0.309-0.809). In overall survival analysis we found a significant association of the FAS 1377G>A (P = 0.040, RR = 0.451, CI = 0.496-1.188) and IL10 592C>A polymorphisms (P = 0.020, RR = 1.707, CI = 1.087-2.680) in the univariate Cox regression. The effect remained statistically significant in the multivariate analysis for the IL10 592C>A polymorphism (P = 0.013, RR 1.841, CI 1.140-2.973). No association was found for MTHFR 677C>T, VEGF 936C>T, CCND1 870G>A, TGFB1 29T>C, FASLG 844C>T, FAS 670A>G, GPB3 825C>T, ITGA2 807C>T, ITGA2 1648G>A, ITGB3 176T>C, MMP1 -1607 1G/2G, MMP3 5A/6A, PTGS2 8473T>C, IL10 592C>A and SULT1A1 638G>A polymorphisms and disease-free survival or overall survival. Our data suggest that the FAS 1377G>A and IL10 592C>A polymorphisms could modify disease-free and overall survival in women with lymph node-positive breast cancer.