Estrogen metabolism genes and transforming growth factor-beta1 gene polymorphisms in estrogen receptor-positive and -negative infiltrating ductal breast carcinoma

Abstract

The aim of our study was to determine the possible association between estrogen receptor status and CYP1A1-6235T/C (rs4646903), SULT1A1-638G/A (rs9282861) and TGFB1-509C>T (rs1800469) genes polymorphism with infiltrating ductal breast carcinoma risk and response to neoadjuvant chemotherapy. Subjects and methods: One hundred sixteen patients with operable primary infiltrating ductal breast carcinoma who received two-four cycles of neoadjuvant chemotherapy in the Tomsk Cancer Research Institute were included in the present study. The healthy women (n=269) from Western Siberian region were used as the control group. Patient characteristics such as estrogen receptor status were evaluated. The genotypes were determined by RFLP-PCR. Results: The ER-positive patients with TGFB1(T/T) genotype had a significantly decreased risk for infiltrating ductal breast carcinoma (p=0,01) than the ER-negative patients. The CYP1A1(T/T) and SULT1A1(G/G) genotypes significantly reduced risk of infiltrating ductal breast carcinoma among the ER-positive patients (p=0,008 and p=0,001, respectively) and the ER-negative patients (p=0,01 and p=0,01, respectively). In addition, both patients groups carrying SULT1A1(A/A) genotype had higher risk for ductal breast carcinoma development (OR=2,02;p=0,002 and OR=1,88;p=0,03, respectively). The ER-positive patients with the TGFB1(C/C) genotype responded more frequently to treatment as compared with negative estrogen receptor status patients (p = 0,09). The CYP1A1(T/T) genotype was found to be associated with a nonstatistically significant better response to neoadjuvant chemotherapy among the ER-positive patients (p=0,09) and the ER-negative patients (p=0,06). Furthermore, ER-positive homozygous for the SULT1A1(A/A) genotype had a poorer response to chemotherapy than patients with ER-negative status (p=0,05). Conclusion: Our study suggested that CYP1A1-6235T/C, SULT1A1-638G/A, TGFB1-509C>T genotypes may be associated with infiltrating ductal breast carcinoma risk and the efficacy neoadjuvant chemotherapy in patients with different estrogen status.