Carcinogenesis Advance Access published online on December 10, 2008
Carcinogenesis, doi:10.1093/carcin/bgn281
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The Association of Interleukin-16 Polymorphisms with IL-16 Serum Levels and Risk of Colorectal and Gastric Cancer
1 Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R.China
2 Department of Cardiology, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041 P.R.China
3 Department of Immunology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R.China
4 Laboratory of Molecular Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R.China
5 Department of Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041 P.R.China
* Corresponding author. Tel: +86-28-85469033; fax: +86-28-85405541, E-mail address: westzh{at}yahoo.com.cn (L. Zhang)
Interleukin-16 (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 (SNPs) 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 (PCR-RFLP) and DNA sequencing methods. Serum IL-16 levels were measured by ELISA. 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 to individuals carrying the T allele. Alternatively, women carrying the T allele (rs4072111 C/T) showed a decreased risk for CRC and GC compared to 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.
Key Words: Interleukin-16 • Polymorphism • Serum levels • Colorectal cancer • Gastric cancer
Lin-Bo Gao and Li Rao contributed equally to this work Received September 12, 2008; revised November 16, 2008; accepted December 6, 2008.