Interleukin-10 promoter polymorphism is associated with decreased breast cancer risk

Abstract

Interleukin-10 (IL-10) is an immunosuppressive cytokine which may facilitate development of cancer by supporting tumor escape from the immune response. A [TCATA] haplotype formed by polymorphisms at positions -3575, -2763, -1082, -819 and -592 in the promoter of the IL-10 gene is a strong determinant for IL-10 expression. The presence of this haplotype can be determined by analysis of the -592C > A polymorphism. Aim of the present study was to analyze the role of the IL-10 [TCATA] haplotype for breast cancer. We performed a case-control study including 500 female patients with histologically confirmed breast cancer and 500 female, age-matched, healthy control subjects from population-based screening studies. The -592C > A polymorphism was determined by a 5'-nuclease assay (TaqMan). Frequency of the homozygous -592 AA genotype, indicating homozygosity for the [TCATA] haplotype, was 4.2% among patients and 7.3% among controls (p=0.038; odds ratio 0.56; 95% confidence interval 0.32-0.97). IL-10 genotypes were not associated with tumor size, histological grading, estrogen or progesterone receptor status and age at diagnosis. Therefore we conclude that the IL-10 -592C > A promoter polymorphism may be associated with a reduced breast cancer risk.

Inflammatory breast cancer: High incidence of GCC haplotypes (−1082A/G, −819T/C, and −592A/C) in the interleukin-10 gene promoter correlates with over-expression of interleukin-10 in patients’ carcinoma tissues

“…35,36,64,65 On the contrary, some other studies found GG genotype as a protective factor against breast cancer, 35,40 and other studies suggested that AA genotype plays a risk factor in breast cancer etiology. 39,40,42 According to the published literatures, only two studies conducted on Egyptian population and included only −1082G/A SNP in IL-10 gene promoter in breast cancer patients and they did not detect any significant difference in distribution of genotypes but the tumor size was significantly larger in breast cancer patients with AA genotype. 37 There are a number of recognition sites in the promoter of the IL-10 gene, including API, PEA1, and an ETS-like element.…”

Inflammatory Cytokine Gene Polymorphisms, Nonsteroidal Anti-Inflammatory Drug Use, and Risk of Adenoma Polyp Recurrence in the Polyp Prevention Trial

“…However, other studies show that high levels of IL-10 may actually be a risk factor for other cancers, hepatocellular, ovarian, melanoma, lymphoma, and myeloma (50). The IL-10 À592 C>A promoter polymorphism has been associated with a reduced breast cancer risk (37) and the IL-10 À1082 G>A polymorphism was associated with increased risk of noncardia gastric cancer (36). Currently, the role of IL-10 in cancer remains unresolved (53).…”

“…Data show that SNPs in the proinflammatory IL-1b, IL-6, and IL-8 genes and in the anti-inflammatory IL-10 gene result in changes in biological functions of the inflammation pathway and have been associated with a number of inflammatory diseases, including inflammatory bowel disease, arthritis, and Alzheimer's disease (29)(30)(31)(32)(33), as well as a number of cancers including colon, stomach, breast, and liver cancer and melanoma of the skin (34)(35)(36)(37)(38)(39)(40).…”

The cyclooxygenase-2 (PTGS2) 8473T>C polymorphism is associated with breast cancer risk.

“…PCR reaction and evaluation of fluorescence data were done as described previously (14). For each set of reactions, one negative control containing water instead of DNA was added to check for contamination.…”