Genetic Variants of Interleukin-8 and Interleukin-16 and Their Association with Cervical Cancer Risk

Cervical cancer (CC) is the fourth most common cancer diagnosis in women worldwide. Infection with high-risk human papillomavirus (HPV) is a critical but not determinative condition for CC development, as several co-factors modulate the progression of HPV-associated cervical lesions. Interleukin-8 (IL-8) and Interleukin-16 (IL-16) are chemokine-like interleukins involved in the pathogenesis of various cancers. Singular studies in Asian populations have suggested a potential role of IL-8 rs4073 (-251 A>T) and IL-16 rs1131445 (3'UTR T>C) in cervical carcinogenesis.

A case-control study was conducted in a European cohort of 339 women, including 126 CC patients and 213 controls. Four common IL-8 SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), rs1126647 (+2767 A>T), and rs2227543 (+1633 C>T), and four IL-16 polymorphism, rs4778889 (-295 T>C), rs11556218 (3441 T>G), rs4072111 (1300 C>T), and rs1131445 (3'UTR T>C), were assessed using RFLP-PCR and analyzed under seven inheritance models. Subgroup analyses were stratified by menopausal status (age threshold 51 years), disease stage, and histological subtype.

IL-16 rs4072111 was significantly associated with an increased CC risk in premenopausal women in the co-dominant (p = 0.038), dominant (p = 0.022), and heterozygote (p = 0.045) models, identifying the T allele as the risk allele (OR 2.31, CI95% 1.17-4.56; p = 0.017). In women aged over 51, IL-16 rs4778889 was associated with CC in the heterozygote (p = 0.048) and overdominant (p = 0.042) models but not in the co-dominant model (p = 0.092). None of the analyzed SNPs significantly increased CC risk in the entire cohort. Specifically, neither IL-16 rs1131445 nor IL-8 rs4073, previously reported as risk factors in Asian populations, were associated with CC risk in this European cohort.

These findings highlight the role of age stage in immunity and cancer susceptibility, suggest that IL-8 and IL-16 SNPs may function differently in cervical carcinogenesis compared with other cancers, and emphasize the importance of ethnic background in cancer risk, warranting further research.