The association of interleukin-16 polymorphisms with IL-16 serum levels and risk of colorectal and gastric cancer

Abstract

Interleukin (IL)-16, a multifunctional cytokine, plays a fundamental role in inflammatory diseases, as well as in the development and progression of tumors. Genetic variation in the DNA sequence of the IL-16 gene may lead to altered cytokine production and/or activity, and this variation may modulate an individual's susceptibility to both colorectal cancer (CRC) and gastric cancer (GC). To test this hypothesis, we investigated the association of IL-16 gene polymorphisms with serum levels of IL-16 and the risk of CRC and GC in a Chinese population. We analyzed single-nucleotide polymorphisms of the IL-16 gene in 596 cancer patients (376 patients with CRC and 220 patients with GC), and also in 480 age- and sex-matched controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. Serum IL-16 levels were measured by enzyme-linked immunosorbent assay. The rs11556218 T/G polymorphism of the IL-16 gene was significantly associated with the susceptibility to CRC and GC patients. Both male and female patients carrying the G allele had a significantly higher risk for developing CRC and GC compared with individuals carrying the T allele. Alternatively, women carrying the T allele (rs4072111 C/T) showed a decreased risk for CRC and GC compared with individuals carrying the C allele. In patients with CRC or GC, IL-16 serum levels were significantly higher than those in the healthy controls, although no significant association between IL-16 polymorphisms and serum levels of IL-16 was observed. Our data indicate that IL-16 polymorphisms may contribute to CRC and GC susceptibility.

Association between interleukin 6 and interleukin 16 gene polymorphisms and coronary heart disease risk in a Chinese population

“…21 The rs4778889 polymorphism has been associated with Graves' disease and asthma, 9 systemic lupus erythematosus, 11 and colorectal and gastric cancer. 10 There was no association between rs4778889 and CAD in the present study, however. This may be explained by differences in population background, the source of control subjects and sample size.…”

“…15 The SNPs rs11556218, rs8034928, rs3848180 and rs4577037 lie within the intron region, whereas rs1131445 and rs4778889 are located in the 3 0 untranslated region. The rs11556218 SNP has been shown to be associated with allergic contact dermatitis, colorectal cancer, endometriosis, gastric cancer, systemic lupus erythematosus, nasopharyngeal carcinoma and renal cell carcinoma, 10,11,[16][17][18][19][20] in addition to CAD risk. 12,21 In accordance with the present study findings, the rs11556218 TG/GG genotypes were previously associated with 1.77-fold increased risk of CAD compared with the TT genotype.…”

Positive Association Between IL-16 rs11556218 T/G Polymorphism and Cancer Risk: a Meta-analysis

“…Nine publications were excluded after reading the full article in detail, because they were editorial comment, letter, case report, other polymorphism of IL-16, without sufficient data, repeated literatures and violated HWE (Thomas et al, 2008;Obara et al, 2010;Azimzadeh et al, 2012;Batai et al, 2012;Lin et al, 2012;Deng et al, 2012;Du, et al, 2012;Hughes et al, 2013;Zhang et al, 2013). The study of Gao et al (2009b) presented separate OR by colorectal and gastric two cancer types and each of them was considered as a separate study. Finally, eight case-control studies from DOI:http://dx.doi.org/10.7314/APJCP.2014.15.11.4697 Positive Association Between IL-16 rs11556218 T/G Polymorphism and Cancer Risk: a Meta-analysis seven publications (6 in English, 1 in Chinese) involving 3944 cases were finally included into the meta-analysis (Gao et al, 2009a;2009b, Zhu et al, 2010Azimzadeh et al, 2011;Li et al, 2011;Zhao et al, 2012;Qin et al, 2014).…”

“…The study of Gao et al (2009b) presented separate OR by colorectal and gastric two cancer types and each of them was considered as a separate study. Finally, eight case-control studies from DOI:http://dx.doi.org/10.7314/APJCP.2014.15.11.4697 Positive Association Between IL-16 rs11556218 T/G Polymorphism and Cancer Risk: a Meta-analysis seven publications (6 in English, 1 in Chinese) involving 3944 cases were finally included into the meta-analysis (Gao et al, 2009a;2009b, Zhu et al, 2010Azimzadeh et al, 2011;Li et al, 2011;Zhao et al, 2012;Qin et al, 2014). The main characteristics of the studies are listed in Table 1.…”

IL-16 Induces Intestinal Inflammation via PepT1 Upregulation in a Pufferfish Model: New Insights into the Molecular Mechanism of Inflammatory Bowel Disease

“…Several previous epidemiological investigations have shown that IL-16 is considerably increased at both the mRNA and protein levels in pathologic intestinal tissues and the systemic circulation of patients with UC and CD compared with healthy control individuals (19,20). Neutralization of IL-16 reportedly attenuates colitis-like inflammation in an experimental mouse model (21).…”