Objective: The purpose of the present study was to evaluate the associations between seven tagging single nucleotide polymorphisms (tSNPs) and risk of breast cancer assessed by tumor pathological characteristics and body mass index (BMI).
Methods: Seven tSNPs of four breast cancer susceptibility genes were analyzed in 734 Chinese women with breast cancer and 672 age-matched healthy controls; then, the association with clinicopathological characteristics, BMI, molecular subtype, TNM (T, tumor; N, lymph node; M, metastasis) staging and lymph node status was determined by unconditional logistic regression.
Results: Rs12951053 in TP53 and rs16945628 in BRIP1, displayed increased risk of breast cancer in the BMI ≧ 25 kg/m² group (OR=1.50, 95% CI: 1.02– 2.21, P=0.041 and OR=1.92, 95% CI: 1.13– 3.26, P=0.015, respectively). The other five tSNPs (rs1805812, rs2735385 and rs6999227 in NBS1, rs7220719 in BRIP1 and rs2299941 in PTEN) displayed a decreased risk of breast cancer in the 18.5≤BMI< 25 kg/m² group. Rs12951053 in TP53 and rs7220719 in BRIP1 exhibited an increased risk of triple‐negative breast cancer (OR=1.50, 95% CI: 1.05– 2.15, P=0.026 and OR=2.13, 95% CI: 1.05– 4.29, P=0.032, respectively), but three tSNPs in NBS1 (rs1805812, rs2735385 and rs6999227) all displayed a negative association with both luminal B and triple-negative breast cancer. The tSNP rs2299941 in PTEN also exhibited a negative association with each molecular subtype, except triple-negative breast cancer. The majority of tSNPs displayed a negative association with stage II or III breast cancer. Most tSNPs showed a negative association with breast cancer that was lymph node negative or with 1– 3 positive nodes. Only rs12951053 in TP53 displayed a positive association with lymph node-negative breast cancer (OR=1.43, 95% CI: 1.08– 1.91, P=0.013).
Conclusion: The majority of tSNPs displayed a negative association with breast cancer and only a few tSNPs (rs12951053 in TP53, rs16945628 and rs7220719 in BRIP1) showed an increased risk of breast cancer as defined by clinicopathological characteristics.
Keywords: breast cancer, SNP, molecular subtype, BRIP1, NBS1