Autophagy ATG16L1 rs2241880 impacts the colorectal cancer risk: A case‐control study

Abstract

Background Despite many efforts to discover the important role of the autophagy process in the pathogenesis of colorectal cancer (CRC), the exact involved molecular mechanism still remains to be elucidated. Recently, a limited number of studies have been employed to discover the impact of autophagy genes’ variants on the development and progression of CRC. Here, we evaluated the association between two single‐nucleotide polymorphisms (SNPs) in the main components of the autophagy genes, ATG16L1 rs2241880, and ATG5 rs1475270, and the CRC risk in an Iranian population. Methods During this investigation, a total of 369 subjects, including 179 CRC patients and 190 non‐cancer controls have been genotyped using Tetra‐primer amplification refractory mutation system‐polymerase chain reaction (TP‐ARMS‐PCR) method. Result The results demonstrated that the T allele of the ATG16L1 rs2241880 was significantly associated with the increased risk of CRC in the studied population (OR 1.64, 95% CI: 1.21–2.22, p = 0.0015). Moreover, ATG16L1 rs2241880 TT genotype increased the susceptibility to CRC (OR 3.31, 95% CI: 1.64–6.69, p = 0.0008). Furthermore, a significant association was observed under the recessive and dominant inheritance models (p = 0.0015 and p = 0.017, respectively). No statistically significant differences were found in the ATG5 rs1475270 alleles and genotypes between the cases and controls. Conclusion The results of the present study may be helpful concerning the risk stratification in CRC patients based on the genotyping approach of autophagy pathways and emphasize the need for further investigations among different populations and ethnicities to refine our conclusions.

The potential importance of autophagy genes expression profile dysregulation and ATG polymorphisms in COVID‐19 pathogenesis

“…Studies have revealed that polymorphisms in the ATG5 promoter such as rs510432 and rs506027 and ATG16L1 (rs2241880) play a role in various immune-mediated, malignancies, or infectious diseases [42,[44][45][46][47][48]. According to the effects of these polymorphisms on the expression of ATGs [49], we examined the association of these genetic variations.…”

“…ATG genes polymorphism can play a role as an element in pathogenesis of different diseases [42,48,49]. In one study, it has been determined that ATG16L1 rs2241880 polymorphisms are related to colorectal cancer risk [48].…”

“…ATG genes polymorphism can play a role as an element in pathogenesis of different diseases [42,48,49]. In one study, it has been determined that ATG16L1 rs2241880 polymorphisms are related to colorectal cancer risk [48]. It has also been found that ATG5 and ATG7 polymorphisms contribute to neutrophilic airway inflammation in asthma and could be a key to the pathogenesis process for asthma in adult patients [42].…”

Association of PNPLA3 (rs738409) & TM6SF2 (rs58542926) and ATG16L1 (rs2241880) genetic variants with susceptibility to hepatocellular carcinoma in a group of Egyptian patients with HCV-induced liver cirrhosis

“…In the primary stages of neoplasia formation, autophagy plays a tumor-suppressive role to maintain normal homeostasis inside the cells. In later stages of cancer formation, autophagy could induce tumor growth, which is the second role of autophagy in carcinogenesis [ 10 ]. The autophagy process is mediated through autophagy-related proteins (ATG).…”

“…The autophagy process is mediated through autophagy-related proteins (ATG). Several studies have shown that the SNPs in ATG genes may be correlated with the risk of many cancers such as melanoma, gastric cancer, colorectal cancer, and HCC [ 10 , 11 ]. The ATG16L1 gene which is located on chromosome 2 plays a vital role in autophagy.…”