IL1 Receptor Antagonist Gene IL1-RN Variable Number of Tandem Repeats Polymorphism and Cancer Risk: A Literature Review and Meta-Analysis

Abstract

IL1 receptor antagonist (IL1RA) and IL1beta (IL1β), members of the pro-inflammatory cytokine interleukin-1 (IL1) family, play a potential role against infection and in the pathogenesis of cancers. The variable number of tandem repeats (VNTR) polymorphism in the second intron of the IL1 receptor antagonist gene (IL1-RN) and a polymorphism in exon 5 of IL1B (IL1B+3954C>T, rs1143634) have been suggested in predisposition to cancer risk. However, studies have shown inconsistent results. To validate any association, a meta-analysis was performed with 14,854 cases and 19,337 controls from 71 published case–control studies for IL1-RN VNTR and 33 eligible studies contained 7,847 cases and 8917 controls for IL1B +3954. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated from comparisons to assess the strength of the association. There was significant association between the IL1-RN VNTR polymorphism and the risk of cancer for any overall comparison. Furthermore, cancer type stratification analysis revealed that there were significantly increased risks of gastric cancer, bladder cancer and other cancer groups. Infection status analysis indicated that the H. pylori or HBV/HCV infection and IL1-RN VNTR genotypes were independent factors for developing gastric or hepatocellular cancers. In addition, a borderline significant association was observed between IL1B+3954 polymorphism and the increased cancer risk. Although some modest bias could not be eliminated, this meta-analysis suggested that the IL1-RN VNTR polymorphisms may contribute to genetic susceptibility to gastric cancer. More studies are needed to further evaluate the role of the IL1B+3954 polymorphism in the etiology of cancer.

Association between cytokine gene polymorphisms and squamous cell lung cancer depending on the duration of smoking in men

“…В настоящей работе не выявлены ассоциации по-лиморфных локусов IL1B (rs1143634, rs16944), IL1rn (rs2234663), tnfa (rs1800629), IL6 (rs1800795) и IL10 (rs1800896) генов цитокинов с риском ПРЛ без уче-та длительности курения. Анализ большинства про-веденных ранее метаанализов тоже не показал зна-чимых ассоциаций полиморфизма в генах цитокинов с раком легкого [18][19][20][21]. Однако при их выполнении не были учтены социальные и средовые факторы, роль которых в патогенезе рака легкого доказана.…”

Polymorphisms in host immune response associated genes and risk of nasopharyngeal carcinoma development in Portugal

“…T carriers were reported as not able to develop an effective response against virus (Omran et al, 2013), nevertheless, when combined with other alleles from other SNPs was associated with a protection to perinatal HIV-1 infection (Pontillo et al, 2012). Many studies have shown that this polymorphism might be associated with several cancers (Ter-Minassian et al, 2008;Zhang et al, 2012;Pooja et al, 2012) but none has yet showed any correlation with NPC. Our study showed no correlation with the risk of NPC development, still studies in population with higher incidence of NPC may help to clarify its role.…”

Association of the IL-1RN variable number of tandem repeat polymorphism and Helicobacter pylori infection: A meta-analysis

“…pylori related-diseases has been extensively investigated [21–23]. One meta-analysis reported that the short genotype of IL-1RN VNTR significantly increases the risk of gastric cancer [24]; another paper found that IL-1RN VNTR has no association with duodenal ulcer [25]. A number of studies performed on H .…”