免疫相关基因 STIM1、ITPKC 和 PELI1 多态性与结直肠癌风险相关。

Immune-related genes STIM1, ITPKC and PELI1 polymorphisms are associated with risk of colorectal cancer.

机构信息

Department of Gastrointestinal and Breast Surgery, The First Affiliated Hospital, School of Medicine, Shihezi University.

Department of Pathology, The First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang.

出版信息

Eur J Cancer Prev. 2021 Sep 1;30(5):357-363. doi: 10.1097/CEJ.0000000000000641.

DOI:10.1097/CEJ.0000000000000641

PMID:33470690

Abstract

OBJECTIVES

STIM1, ITPKC and PELI1 are all immune-related genes that take part in the T cell activation, toll-like receptor and IL1 receptor pathways. The goal of this study was to evaluate the associations between STIM1, ITPKC and PELI1 polymorphisms and colorectal cancer (CRC) risk.

METHODS

Six single nucleotide polymorphisms (SNPs) in STIM1, ITPKC and PELI1 were genotyped using a MassARRAY platform in a discovery cohort including 480 CRC cases and 480 healthy individuals and validated in a replication cohort including 505 CRC cases and 510 controls.

RESULTS

The minor alleles of rs3794050, rs3750996 and rs2607420 were associated with an increased CRC risk (P < 0.05). In contrast, the minor allele of rs329497 was correlated with reduced disease risk (P = 0.025). Genetic model analysis showed that rs3794050 was related to an increased risk of disease in recessive and log-additive models (P < 0.05); rs3750996 had a strong correlation with CRC risk under all genetic models (P < 0.02); rs2607420 was correlated with an increased risk of disease in dominant and log-additive models (P < 0.01); whereas the protective effect of rs329497 on CRC risk was observed in dominant and log-additive models (P < 0.05). Finally, the association between the above SNPs and CRC risk was validated in a replication cohort (P < 0.05).

CONCLUSIONS

Our results could be helpful for the early screening of individuals with high CRC risk.

摘要

目的

STIM1、ITPKC 和 PELI1 均为参与 T 细胞激活、Toll 样受体和 IL1 受体途径的免疫相关基因。本研究旨在评估 STIM1、ITPKC 和 PELI1 多态性与结直肠癌（CRC）风险之间的关系。

方法

使用 MassARRAY 平台在包含 480 例 CRC 病例和 480 例健康个体的发现队列中对 STIM1、ITPKC 和 PELI1 中的 6 个单核苷酸多态性（SNP）进行基因分型，并在包含 505 例 CRC 病例和 510 例对照的验证队列中进行验证。

结果

rs3794050、rs3750996 和 rs2607420 的次要等位基因与 CRC 风险增加相关（P<0.05）。相比之下，rs329497 的次要等位基因与疾病风险降低相关（P=0.025）。遗传模型分析表明，rs3794050 在隐性和对数相加模型中与疾病风险增加相关（P<0.05）；rs3750996 在所有遗传模型中均与 CRC 风险密切相关（P<0.02）；rs2607420 与显性和对数相加模型中的疾病风险增加相关（P<0.01）；而 rs329497 对 CRC 风险的保护作用在显性和对数相加模型中观察到（P<0.05）。最后，在验证队列中验证了上述 SNP 与 CRC 风险的关联（P<0.05）。