Functional variants in the promoter of interleukin‐1β are associated with an increased risk of breast cancer: A case‐control analysis in a Chinese population

Interleukin 1β (IL‐1β) 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‐1β gene promoter were suggested to be correlated with alteration of IL‐1β 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‐1β‐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‐1β‐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‐1βT‐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‐1β promoter variants may contribute to risk of developing breast cancer in the Chinese population. © 2005 Wiley‐Liss, Inc.