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Background  Immune system-related receptors CD40 (tumor necrosis factor receptor superfamily member 5), BAFFR (tumor necrosis factor receptor superfamily member 13C), and LTβR (tumor necrosis factor receptor superfamily member 3) play a pivotal role in non-small-cell lung cancer (NSCLC). To further evaluate their role in NSCLC,  CD40  rs1883832 (T>C),  BAFFR  rs7290134 (A>G), and  LTβR  rs10849448 (A>G) single-nucleotide polymorphisms (SNPs) were investigated regarding their impact in risk and clinical outcome of NSCLC patients.    Methods  The three selected SNPs were evaluated in 229 NSCLC patients and 299 healthy controls, while CD40, BAFFR, and LTβR protein expression was assessed by immunohistochemistry in 96 tumor specimens from NSCLC patients.    Results  In total,  CD40  rs1883832 was associated with NSCLC risk, with the T allele, after adjusting for cofactors, being related to increased risk (p = 0.007; OR 1.701). Moreover, the CT genotype was associated with increased risk (p = 0.024; OR 1.606) and poorer 5-year overall survival (OS) after adjusting for cofactors (p = 0.001, HR 1.829), while CC was associated with higher CD40 expression in tumorous cells (p = 0.040) and in stromal cells (p = 0.036). In addition, AA homozygotes for the  LTβR  rs10849448 had increased risk for NSCLC in multivariate analysis (p = 0.008; OR, 2.106) and higher LTβR membranous expression (p = 0.035). Although  BAFFR  rs7290134 was associated with BAFFR membranous expression (p = 0.039),  BAFFR  rs7290134 was not associated with neither the disease risk nor the prognosis of NSCLC patients.    Conclusions  In conclusion,  CD40  rs1883832 and  LTβR  rs10849448 seem to be associated with increased risk for NSCLC, while  CD40  rs1883832 is also associated with OS of patients with NSCLC.

Genetic Variations of CD40 and LTβR Genes Are Associated With Increased Susceptibility and Clinical Outcome of Non-Small-Cell Carcinoma Patients