Association of IL-1β 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-1β polymorphisms and BC and TNBC susceptibility.

Methods

Genotyping of IL-1β rs1143627, 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-1β genetic polymorphisms and BC and TNBC susceptibility, suggesting these variants’ diagnostic/prognostic capacity in BC patients.