Association of single nucleotide autophagy‐related protein 5 gene polymorphism rs2245214 with susceptibility to non–small cell lung cancer

Abstract

Introduction: Autophagy is a mechanism that is involved in the regulation of cellular life, apoptosis, and stemness while its intervening genes play important functions in various cancers including lung cancer. ATG5 is one of the key genes for the regulation of the autophagy pathway. In this study, our team has investigated the potential relationship between ATG5 gene polymorphism rs2245214 with non–small cell lung cancer (NSCLC) in a subpopulation of patients from southern Iran. In this study, 34 patients with NSCLC (20 males and 14 females [mean age: 12.86 ± 60.47 years]) and 50 healthy subjects (30 males and 20 females [mean age: 13.09 ± 56.62 years]) were studied in terms of the genotype of the ATG5 gene. We used restriction fragment length polymorphism and analyzed the results using SPSS software (v.23). The results revealed that subjects harboring the guanine/cytosine (GC) genotype of the rs2245214 ATG5 gene polymorphism had suffered less from NSCLC, whereas the prevalence of the C‐allele of this polymorphism was significantly higher in patients with NSCLC ( P < 0.05). On the basis of the results of logistic regression, the presence of this C‐allele may predict the risk of lung cancer ( P value = 0.011; OR, 3.52; 95% CI, 1.33‐9.26). This study concludes that the C‐allele of the rs2245214 ATG5 gene polymorphism is associated with increased susceptibility to NSCLC, whereas the GC genotype of this polymorphism is associated with decreased risk and might therefore have a protective role in the development of NSCLC.

Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis, Impact on Disease Development/Progression, and Potential as Therapeutic Targets

“…Autophagy induction in tumor cells is related to many factors, including the occurrence of ROS and the unfolded protein response [ 115 ]. Its occurrence correlates with diverse genetic polymorphisms and levels of specific proteins such as S100A8/A9, of which the involvement in the induction of autophagy was described by Ghavami et al in 2010 [ 116 , 117 ].…”

ATG5: A central autophagy regulator implicated in various human diseases

“…No significant associations were found in both. However, the same polymorphism was found to be protective in the case of non‐small‐cell lung cancer in the Iranian population and the case of risk of Q fever caused by Coxiella burnetii in recent studies 181,182 …”

Pathogenic Single Nucleotide Polymorphisms on Autophagy-Related Genes

“…For example, pathogenic alleles of ATG5 , ATG10 , ATG12 and ATG16L1 have been all linked to changes in susceptibility or treatment efficiency in neck squamous cell cancer [ 103 , 114 , 115 , 116 ], hepatocellular carcinoma [ 117 ] and lung adenocarcinoma [ 118 ] and others have been found to also affect development of other types of cancer, such as melanoma [ 119 ], brain metastases in patients with non-small lung cancer [ 120 ] or breast cancer [ 121 , 122 , 123 , 124 ]. Moreover, there is also an association between SNPs in ATG5 and ATG7 with clear cell renal cell carcinoma [ 125 ] and variants of ATG5 and ATG10 have been linked to non-small cell lung cancer [ 126 , 127 ]. Additional connections between changes on these genes and cancer are those of ATG5 in multiple myeloma [ 128 ] or non-medullary thyroid cancer [ 129 ].…”