| Summary: | Abstract Background Tumor necrosis factor superfamily member 15 (TNFSF15) is closely related to tumorigenesis and development. This study aimed to investigate the correlations between TNFSF15 polymorphisms and genetic susceptibility to lung cancer. Methods This case-control study included 209 small cell lung cancer patients (SCLC), 340 non- small cell lung cancer patients (NSCLC) and 460 health controls. TNFSF15–638 A > G and − 358 T > C polymorphisms were genotyped by polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated by unconditional logistic regression. Results Our results showed that subjects carrying the TNFSF15–638GG genotype or -358CC genotype were more likely to develop SCLC (−638GG, OR = 1.84, 95%CI = 1.13–2.99; -358CC, OR = 2.44, 95%CI = 1.46–4.06), but not NSCLC (P > 0.05). In stratified analysis, −638GG genotype was related to SCLC among males (OR = 1.95, 95%CI = 1.09–3.45, P = 0.023) and older patients (OR = 2.93, 95%CI = 1.44–8.68, P = 0.006). However, -358CC genotype was associated with SCLC among females (OR = 8.42, 95%CI = 2.22–31.89, P = 0.002) and older subjects with OR (95%CI) of 11.04 (3.57–34.15) (P < 0.001). Moreover, TNFSF15 -358CC was linked with a higher risk of SCLC among non-smokers (OR = 2.54, 95%CI = 1.20–5.35, P = 0.015) but not among smokers (OR = 1.88, 95%CI = 0.92–3.84, P = 0.086). Conclusion These findings highlight the importance of TNFSF15 polymorphisms in the development of SCLC.
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