Immune Response-Related Genes - STAT4, IL8RA and CCR7 Polymorphisms in Lung Cancer: A Case-Control Study in China

Pharmgenomics Pers Med. 2020 Oct 21:13:511-519. doi: 10.2147/PGPM.S271983. eCollection 2020.

Abstract

Purpose: This study aimed to evaluate the associations between immune response-related genes - STAT4, IL8RA and CCR7 polymorphisms and risk of lung cancer.

Methods: Seven polymorphisms of STAT4, IL8RA and CCR7 were genotyped in 350 cases and 350 controls using a MassARRAY platform.

Results: The STAT4 rs1400656-G and rs7574865-T alleles may decrease the susceptibility to lung cancer (p rs1400656= 0.020; p rs7574865= 0.014); while IL8RA rs1008562-C and CCR7 rs3136685-T alleles may increase the risk of disease (p rs1008562< 0.001; p rs3136685= 0.018). The STAT4 rs1400656-GA and rs7574865-GT genotypes were determined as protective genotypes against lung cancer risk (p rs1400656= 0.048; p rs7574865= 0.042). However, IL8RA rs1008562-CG/GG and CCR7 rs3136685-TT genotypes were significantly associated with an elevated risk of disease (p rs1008562< 0.0001; p rs3136685= 0.020). Genetic model analysis revealed that STAT4 rs1400656 and rs7574865 were relate to a declining risk of disease under dominant and log-additive models (rs1400656: p dominant = 0.014, p log-additive= 0.016; rs7574865: p dominant = 0.013, p log-additive= 0.013). In contrast, IL8RA rs1008562 exhibited a strong correlation with an elevated risk of lung cancer under all three models (p dominant < 0.0001, p recessive = 0.011, p log-additive< 0.0001). Moreover, CCR7 rs3136685 was correlated with an increased risk of disease under recessive and log-additive models (p recessive = 0.007, p log-additive= 0.019); and CCR7 rs17708087 was also identified as a risk factor in the dominant model (p = 0.038).

Conclusion: These results widen the scope of knowledge about the association between STAT4, IL8RA and CCR7 polymorphisms and risk of lung cancer.

Keywords: CCR7; Chemokine (C-C motif) receptor 7; IL8RA; SNPs; STAT4; interleukin 8-receptor alpha; lung cancer; signal transducers and activators of transcription 4; single nucleotide polymorphisms.