4‐bp insertion/deletion (rs3783553) polymorphism within the 3′UTR of IL1A contributes to the risk of prostate cancer in a sample of Iranian population

Abstract

Growing evidence demonstrated the presence of an association between IL1A rs3783553 polymorphism and the risk of various cancers. We aimed to evaluate whether the 4-bp insertion/deletion polymorphism (rs3783553) within the 3' untranslated region (3'UTRs) of IL1A was associated to the risk of prostate cancer (PCa) in a sample of Iranian population. A case-control study, including 150 prostate cancer patients and 155 healthy men, was done to examine the possible association between IL1A 4-bp ins/del polymorphism and PCa risk in a sample of southeast Iranian population. Mismatched polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was designed for genotyping the studied variant. Our findings showed that 4-bp ins/del polymorphism significantly increased the risk of PCa in codominant, recessive and allelic inheritance model. We also evaluated the association between the IL1A 4-bp ins/del polymorphism and clinicopathological characteristics of the patients, and found a significant association between 4-bp ins/del variant and stage, perineural invasion and surgical margin of tumor samples. Bioinformatics analysis revealed that the ins/del variant affected the IL1A mRNA stability leading to a structural shift in IL1A mRNA and has-miR-125a-3p hybrid. In conclusion, our findings proposed an association between IL1A 4-bp ins/del polymorphism and PCa risk. Additional studies with enlarged sample size and diverse ethnicities are required to validate our finding.

Targeted exome sequencing identifies five novel loci at genome-wide significance for modulating antidepressant response in patients with major depressive disorder

“…genome-wide significance in previous GWAS of related phenotypes. For example, the 4-bp indel at rs3783553 and rs3783550 SNP at IL1A identified in this study have previously been reported to be associated with various cancers and severe inflammatory diseases, such as ankylosing spondylitis mostly in Asian populations, including Chinese Han 52,53 . The rs3783550 SNP at IL1A was also found to be in perfect LD (R 2 = 0.197 and D′ = 1) with the rs11677416 SNP at CKAP2L-IL1A, which has been found to have a strong signal for antipsychotic response in patients with schizophrenia treated with olanzapine 54 .…”

Correlation Between Single Nucleotide Polymorphisms in Cxcr4 Microrna Binding Site and the Susceptibility to Knee Osteoarthritis in Han Chinese Population

“…Generally, the 3′-UTR of a gene has a regulatory region for gene expression. Gene mutations in the regulatory region can affect regulation of gene expression; therefore, SNPs in regulatory region are related to the occurrence and development of several diseases (An et al 2006;Hashemi et al 2018;Revathidevi et al 2016;Seegers et al 2002). The rs1804029 site is located at the 3′-UTR targeted binding site of hsa-miR-146a-3p on CXCR4.…”

Effect of polymorphism on IL1A to cancer susceptibility: Evidence based on 34,016 subjects

“…In the past decades, lots of researches stated the connection between cancer risk and IL1A polymorphisms, but the conclusions were contradictory. Some casecontrol studies reported a high risk of cancer susceptibility with IL1A polymorphism [47,61] . On the contrary, others suggested a low risk in the same polymorphism and the same kind cancer [45,60] .…”

“…In term of rs3783553, it is a contention of a hundred schools of thought. It includes researches on multiple systems of cancer diseases, such as hepatocellular carcinoma, nasopharyngeal cancer, glioma, prostate cancer, gastric cancer, thyroid carcinoma, oral squamous cell carcinoma, cervical cancer, ovarian cancer, colorectal cancer, colorectal cancer, and endometrial cancer [37,[45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] . Analyzed by ethnicity, most of studies focus on Asians, yet researches direct to Caucasians are also quite a lot.…”