Jamali Leila, Sadeghi Hossein, Ghasemi Mohammad-Reza, Mohseni Roohollah, Nazemalhosseini-Mojarad Ehsan, Yassaee Vahid Reza, Larki Pegah, Zali Mohammad Reza, Mirfakhraie Reza
Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Clin Lab Anal. 2022 Jan;36(1):e24169. doi: 10.1002/jcla.24169. Epub 2021 Dec 11.
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.
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.
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.
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.
尽管人们为揭示自噬过程在结直肠癌（CRC）发病机制中的重要作用付出了诸多努力，但其确切的分子机制仍有待阐明。最近，已有少数研究致力于探究自噬基因变异对CRC发生发展的影响。在此，我们评估了自噬基因主要成分中的两个单核苷酸多态性（SNP），即ATG16L1 rs2241880和ATG5 rs1475270，与伊朗人群CRC风险之间的关联。
在本研究中，共369名受试者，包括179例CRC患者和190名非癌对照，采用四引物扩增阻滞突变系统-聚合酶链反应（TP-ARMS-PCR）方法进行基因分型。
结果表明，在研究人群中，ATG16L1 rs2241880的T等位基因与CRC风险增加显著相关（比值比1.64，95%置信区间：1.21 - 2.22，p = 0.0015）。此外，ATG16L1 rs2241880的TT基因型增加了患CRC的易感性（比值比3.31，95%置信区间：1.64 - 6.69，p = 0.0008）。此外，在隐性和显性遗传模型下均观察到显著关联（分别为p = 0.0015和p = 0.017）。病例组和对照组在ATG5 rs1475270等位基因和基因型方面未发现统计学显著差异。
本研究结果可能有助于基于自噬途径的基因分型方法对CRC患者进行风险分层，并强调需要在不同人群和种族中进一步开展研究以完善我们的结论。
