Interleukin-6 -572G/C polymorphism and prostate cancer susceptibility

Abstract

ABSTRACT. Strong evidence suggests that cancer-associated inflammation promotes tumor growth and progression, and interleukin-6 (IL6) is an important modulator of inflammation. However, the roles of IL6 and mutations of its corresponding gene in prostate cancer have not been clearly documented. We retrieved data from the Oncomine database concerning IL6 expression in prostate cancer and its role in prostatespecific antigen (PSA) recurrence. We also performed a case-control study of the IL6 -572G/C polymorphism (rs1800796) in 236 sporadic prostate cancer patients and 256 healthy controls from a southern Han Chinese population. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between rs1800796 and prostate cancer susceptibility. A dual-luciferase reporter assay was used to test the transcriptional activity of the IL6 promoter G and C alleles. IL6 was overexpressed in prostate cancer tissues compared to normal tissues, especially in those with higher Gleason scores. Moreover, elevated IL6 expression was associated with high PSA recurrence rate in Oncomine data. Our case-control study demonstrated that compared with the -572C allele, the -572G allele conferred a borderline increased risk of prostate cancer (OR = 1.31, 95%CI = 0.99-1.74, P = 0.061). This was more pronounced in the subgroup of individuals having never smoked (OR = 1.85, 95%CI = 1.07-3.22). Moreover, the G allele showed increased activity relative to the C allele in the dual-luciferase reporter assay. Our results suggest that the -572G/C polymorphism may be associated with IL6 expression, which in turn plays a role in prostate cancer development.

Association of interleukin‐6 polymorphisms with obesity or metabolic traits in young Mexican‐Americans

“…Elevated levels of IL6 are typically associated with obesity-related inflammation and type 2 diabetes in adolescents and adults with obesity (2,3). One recent study found higher promoter activity of the rs1800796 G-allele compared with the C-allele (32). Interestingly, in this study, rs1800796-CC homozygotes had lower plasma IL6 levels when compared with G-allele carriers.…”

Increased expression of interleukin-6 gene in gastritis and gastric cancer

“…Jurečekova et al ( 12 ) also observed an increase in IL-6 mRNA expression but did not find any association between the presence of the rs1800795 polymorphism and the alterations of its gene expression. Nevertheless, Huang et al ( 29 ) demonstrated that the presence of the rs1800796 polymorphism is able to modulate the transcriptional activity of the IL-6 gene, resulting in a high risk of prostate cancer. The meta-analysis by Peng et al ( 14 ) showed that the three polymorphisms influence the expression of IL-6 , contributing to the progression of cancer.…”