Interleukin-1 and Interleukin-6 Gene Polymorphisms and the Risk of Breast Cancer in Caucasian Women

Abstract

Purpose: Genetic polymorphisms of cytokine-encoding genes are known to predispose to malignant disease. Interleukin (IL)-1 and IL-6 are crucially involved in breast carcinogenesis. Whether polymorphisms of the genes encoding IL-1 (IL1) and IL-6 (IL6) also influence breast cancer risk is unknown. Experimental Design: In the present case-control study, we ascertained three polymorphisms of the IL1gene cluster [À889 C/T polymorphism of the IL1a gene (IL1A), À511C/T polymorphism of the IL1b promoter (IL1B promoter), a polymorphism of IL1b exon 5 (IL1B exon 5)], an 86-bp repeat in intron 2 of the IL1 receptor antagonist gene (IL1RN), and the À174 G/C polymorphism of the IL6 gene (IL6) in 269 patients with breast cancer and 227 healthy controls using PCR and pyrosequencing. Results: Polymorphisms within the IL1 gene cluster and the respective haplotypes were not associated with the presence and the phenotype of breast cancer. The IL6 polymorphism was significantly associated with breast cancer. Odds ratios for women with one or two high-risk alleles versus women homozygous for the low-risk allele were 1.5 (95% confidence interval, 1.04-2.3; P = 0.04) and 2.0 (95% confidence interval, 1.1-3.6; P = 0.02), respectively. No association was ascertained between presence of the IL6 polymorphism and various clinicopathologic variables. Conclusions: Although polymorphisms within the IL1 gene cluster do not seem to influence breast cancer risk or phenotype, presence of the À174C IL6 allele increases the risk of breast cancer in Caucasian women in a dose-dependent fashion.

Polymorphisms in promoter regions of IL-6 and IL-10 genes in breast cancer: a case-control study

“…Our results showed that the prevalence of the CC genotype was significantly higher among the cancer patients. These findings are consistent with Hefler et al (2005), who also observed a higher incidence of the CC genotype among Caucasian women with breast cancer.…”

“…In addition to numerous other mechanisms, involvement of cytokines in the progression and pathogenesis of cancer has been observed in various patient cohorts (Smyth et al, 2004;Pooja et al, 2012). For instance, the cytokines interleukin (IL)-1, IL-4, IL-6, and IL-10 are important biomarkers for breast cancer pathogenesis and prognosis (Hefler et al, 2005).…”

Cancer-related fatigue: Links with inflammation in cancer patients and survivors

“…One of the primary factors that influence cytokine expression levels is genetic variation or gene polymorphisms. Cytokine gene polymorphisms have been linked to cancer susceptibility and severity (Hefler et al, 2005), and to physiological responses to cancer treatment (Andreassen et al, 2005). To determine whether differences in single nucleotide polymorphisms (SNPs) might contribute to persistent post-treatment fatigue, we recently examined SNPs in the promoter regions of 3 cytokine genes [IL-1β -511 (T/C), IL-6 -174 (G/C), and IL-6R -183 (G/A)] in fatigued and nonfatigued breast cancer survivors (Collado-Hidalgo et al, 2007).…”

Interleukin-6 plasma level increases with age in an Italian elderly population (“The Treviso Longeva”–Trelong–study) with a sex-specific contribution of rs1800795 polymorphism

“…A single nucleotide polymorphism (SNP), named rs1800795 (consisting of a G → C transversion in position −174 from the transcription start site) located in the promoter region of the IL-6 gene (NM_000600) reduces IL-6 production at the transcriptional level (Fishman et al 1998). The presence of the rs1800795 C-allele has been associated with a mild phenotype of inflammation-triggering pathologies (Hefler et al 2005, Sawczenko et al 2005. The role of rs1800795 in longevity has been explored in the Italian population with conflicting results (Bonafè et al 2001;Capurso et al 2004;Christiansen et al 2004;Hurme et al 2005).…”