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

Background: 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. Methods: 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. Results: 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. Conclusions: 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.