Association of IL-1ß gene polymorphisms rs1143627, rs1799916, and rs16944 with altered risk of triple-negative breast cancer.

PURPOSE: Breast cancer (BC) is the most recognized malignancy in females globally and is heterogeneous in its clinical manifestation, among which the triple-negative (TNBC) subtype is the most aggressive. This study examines the associations between IL-1ß polymorphisms and BC and TNBC susceptibility. METHODS: Genotyping ofIL-1ßrs1143627, rs1799916, and rs16944 polymorphisms was done in 488 women with BC (130 TNBC, 358 non-TNBC) and 476 cancer-free control women using real-time PCR genotyping. RESULTS: The minor allele and genotype frequencies of rs1799916, rs1143627, and rs16944 significantly differed among BC cases and controls and remained after correcting key covariates. On the other hand, minor allele and genotype frequencies of only rs16944 significantly differed between TNBC and non-TNBC cases. Spearman correlation analyses demonstrated that all three variants correlated positively with menopausal status and Her2 status but negatively with menarche, breastfeeding, and cancer type. In addition, rs1143627 and rs16944 correlated positively with HR and ER, while rs1799916 correlated positively with Ki67 status. The three variants correlated negatively with menarche, breastfeeding, and cancer type in non-TNBC cases but positively with histological grading in non-TNBC and Her2 in TNBC cases. A positive correlation was noted between rs1143627 and rs1799916 and age (<40 years) and between rs1799916 and rs16944 with menopausal status. We confirmed that GCG haplotype imparted BC susceptibility, while TCA and TTG haplotypes were protective of BC. Among TNBC cases, only GCG and TCA haplotypes remained protective of TNBC after adjustment. CONCLUSIONS: Our study highlights the association between IL-1ßgenetic polymorphisms and BC and TNBC susceptibility, suggesting these variants' diagnostic/prognostic capacity in BC patients.

Common matrix metalloproteinase-2 gene variants and altered susceptibility to breast cancer and associated features in Tunisian women.

A role for matrix metalloproteinase polymorphisms in breast cancer development and progression was proposed, but with inconclusive results. We assessed the relation of matrix metalloproteinase-2 variants with breast cancer and related phenotypes in Tunisians. This case-control retrospective study involved 430 women with breast cancer and 498 healthy controls. Genotyping of matrix metalloproteinase-2 rs243866, rs243865, rs243864, and rs2285053 was analyzed by allelic exclusion. The minor allele frequency of rs2285053 was significantly lower in women with breast cancer cases as compared to control women; minor allele frequencies of the remaining single-nucleotide polymorphisms were similar between cases and control women. The distribution of rs243865 and rs2285053 genotypes was significantly different between breast cancer patients and control subjects. This persisted when key covariates were controlled for. None of the matrix metalloproteinase-2 variants were associated with estrogen receptor positivity, progesterone receptor positivity, or with double estrogen receptor-progesterone receptor positivity in breast cancer patients. Matrix metalloproteinase-2 rs243866, rs243865, and rs243864 were positively associated with menstrual irregularity and histological type, while rs243866 and rs2285053 were negatively associated with menarche and nodal status. In addition, rs2285053 was negatively associated with triple negativity, tumor size, distance metastasis, molecular type, and chemotherapy. Haploview analysis revealed high linkage disequilibrium between matrix metalloproteinase-2 variants. Four-locus Haploview analysis identified haplotypes GCTT and GTTC to be negatively associated with breast cancer, which remained statistically after controlling for key covariates. Matrix metalloproteinase-2 alleles and genotypes, along with four-locus haplotypes, are related to reduced susceptibility to breast cancer in Tunisian women, suggesting a protective effect.