Functional variants in the promoter of interleukin-1beta are associated with an increased risk of breast cancer: a case-control analysis in a Chinese population.

Interleukin 1beta (IL-1beta) is a multifunctional cytokine that upregulates the inflammatory response, and participates in carcinogenesis, malignant transformation, tumor growth, invasion and metastasis. Two potentially functional polymorphisms (T-31C and C-511T) in the IL-1beta gene promoter were suggested to be correlated with alteration of IL-1beta expression and therefore may be associated with cancer risk. To test the hypothesis that these 2 polymorphisms are associated with risk of breast cancer, we performed a case-control study of 365 breast cancer cases, 270 patients with benign breast diseases (BBD) and 631 cancer-free controls in a Chinese population. Multivariate logistic regression analyses revealed that increased risk of breast cancer was associated with IL-1beta-31C variant genotypes [adjusted odds ratio (OR)=1.28 and 95% confidence interval (CI)=0.91-1.80 for -31CT and 1.72 (95% CI=1.16-2.54) for -31CC], compared with the -31TT genotype. Similarly, IL-1beta-511T variant genotypes were also associated with increased risk of breast cancer (adjusted OR=1.20, 95% CI=0.86-1.67 for -511CT and adjusted OR=1.74, 95% CI=1.18-2.56 for -511TT), compared with the -511CC genotype. Furthermore, cancer risks associated with IL-1betaT-31C variant genotypes were more evident in older women, postmenopausal women and individuals with a later menarche age. Interestingly, although we did not find significant associations of these 2 variants with cancer risk when compared with the BBD patients, a 1.27-fold (95% CI=1.01-1.60) increased risk was observed with the -31C-511T common haplotype. These findings indicate that these 2 IL-1beta promoter variants may contribute to risk of developing breast cancer in the Chinese population. Copyright (c) 2005 Wiley-Liss, Inc.