Association Between IL-4 and IL-6 Expression Variants and Gastric Cancer Among Portuguese Population

Abstract

IntroductionMultiple studies have reported strong associations between Helicobacter pylori (Hp) inflammation and gastric cancer (GC) development. Altered expressions of pro/anti-inflammatory cytokines have a crucial role in Hp and GC proliferation. Although there are many studies related to cytokines polymorphisms involvement in GC risk, the role of Interleukin-4 (IL-4) and Interleukin-6 (IL-6) in gastric inflammation process is not yet clarified.AimThis study aimed to investigate the impact of common IL-4 and IL-6 polymorphisms in GC development risk among Portuguese population.MethodsA total of 100 GC biopsies (50 with intestinal type, IGC, 50 with diffuse type, DGC) and 50 chronic gastritis cases, used as control group, were included in this case-control study. IL-4 and IL-6 common polymorphisms were genotyped by PCR-SSP, using commercially available kits.ResultsIL-4 low producer genotypes, IL-4-590TT (OR = 6.7; 95% CI 1.4–32.4) and IL-4-1098GG (OR = 4.4; 95% CI 1.7–16.9) were found associated with IGC and DGC, respectively. We also verified that IL-4 TTT haplotype was linked with both IGC (OR = 5.8; 95% CI 2.3–14.4) and DGC (OR = 2.3; 95% CI 1.0–5.5) groups. Concerning IL-6 results, IL-6-174CG genotype showed a higher prevalence among IGC cases (OR = 7.3; 95% CI 2.7–20.3), and IL-6-174CC (OR = 3.8; 95% CI 1.7–8.7) showed upper prevalence within DGC subjects. Finally, IL-6-174/nt565CG haplotype showed a significant association with both IGC (OR = 7.3; 95% CI 2.7–20.3) and DGC (OR = 7.9; 95% CI 4.2–14.9).ConclusionIL-6 and IL-4 expression variants seem to have an important role in GC risk mechanisms. This study provides preliminary evidence that IL-4 and IL-6 polymorphisms, although not directly linked to the disease, may be useful tools in the study of this multifactorial disease.

Association of angiogenesis and inflammation‑related gene functional polymorphisms with early‑stage breast cancer prognosis

“…Several authors have demonstrated that carrying the IL-6 rs1800795 G or IL-6 rs1800795 G alleles is associated with higher IL-6 protein production (19)(20)(21). Specifically, IL-6 is a cytokine which is considered a prognostic marker as well as a potential therapeutic target for BC patients.…”

“…Common polymorphisms in proinflammatory and proangiogenic cytokine genes may influence their coded protein production and play a role in the course of BC. The polymorphisms with proved functional activity are VEGFA (rs699947, rs833061, rs25648, rs1005230), IL-1β (rs1143634, rs16944), IL-1α (rs1800587) and IL-6 (rs1800795, rs1800797) (14)(15)(16)(17)(18)(19)(20)(21). Candidate gene studies as well as moderate-sized genome-wide association studies (GWAS) highlight the important role of these polymorphisms in BC risk and aggressiveness (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32), although substantial heterogeneity across studies exists.…”

IL-6 and miR-1271 expression levels in elderly and young gastric cancer patients and correlation analysis with prognosis

“…The expression level of IL-6 was higher in elderly gastric cancer than that in young gastric cancer, probably because the elderly usually have low immune function, susceptible to inflammatory infections (25). Sampaio et al (26) found that IL-6, highly expressed in gastric cancer tissues, is correlated with tumor size and the T stage of gastric cancer. The results of this study are consistent with those of Sampaio et al (26).…”

Association of IL-6 −174 G>C Polymorphism with Susceptibility to Colorectal Cancer and Gastric Cancer: a Systematic Review and Meta-Analysis

“…7,560 cases and 9,574 controls were on CRC (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), and 13 studies with 1,445 cases and 2,918 controls were on GC (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). These included studies were published between 2003 and 2017.…”