The effect of TP53 and P21 gene polymorphisms on papillary thyroid carcinoma susceptibility and clinical/pathological features

Abstract

Papillary thyroid cancer (PTC) is the most common thyroid malignancy. Genetic polymorphisms of the TP53 and P21 genes are the candidate variants in various cancers development. This study investigated whether the polymorphisms in TP53 (rs1042522) and P21 (rs1059234 and rs1801270) affect the risk of PTC and whether such the genotype of these polymorphisms is associated with pathological and clinical characteristics of PTC. A case–control study was conducted with 286 Iranian people, including 131 PTC cases and 155 healthy controls. The genetic polymorphisms were investigated by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Our results suggested that TP53‐rs1042522 CC genotype was significantly associated with protection against PTC, in the dominant, recessive and allelic models (OR = 0.4, 95%CI: 0.2–0.8, P = .008; OR = 0.5, 95%CI: 0.3–0.9, P = .01; OR = 0.6, 95%CI: 0.4–0.8, P = .002, respectively). The rs1042522 was associated with PTC patients with tumor size greater than 1 cm in dominant and recessive models (OR = 0.2, 95%CI = 0.04–0.9, P = .04 and OR = 0.3, 95%CI = 0.1–0.7, P = .009, respectively) and was associated with vascular invasion in dominant model (OR = 0.3, 95%CI = 0.1–0.7, P = .01). No correlation was identified between P21 rs1059234 and rs1801270 polymorphisms and risk of PTC and pathological and clinical characteristics of PTC. Genetic variations in rs1042522 might alter the PTC risk, which could affect tumor size and cause lower incidence of vascular invasion in PTC cases. This was the first report suggesting that no correlation was found between P21 rs1059234 and rs1801270 polymorphisms and PTC risk. Thus, more studies with a larger population size and different ethnic groups and functional assays are needed to confirm our results.

Three‐dimensional nuclear architecture distinguishes thyroid cancer histotypes

“…Indeed, this variant is considered benign in the ClinVar archive according to the American College of Medical Genetics and Genomics (ACMG) criteria, and recently the effect of TP53-rs1042522 variants on decreased risk of PTC, smaller tumor size and lower incidence of vascular invasion was described. 50 Nevertheless, we observed that NIFTP nodules with these variants had significant differences in chromatin condensation (P = .0002). Further study of cases with the same variant will clarify if this association may characterize a subtype of NIFTPs.…”

“…The arg allele of rs1042522 is slightly more active in inducing apoptosis 49 and it has been associated with winter temperature. Indeed, this variant is considered benign in the ClinVar archive according to the American College of Medical Genetics and Genomics (ACMG) criteria, and recently the effect of TP53 ‐rs1042522 variants on decreased risk of PTC, smaller tumor size and lower incidence of vascular invasion was described 50 . Nevertheless, we observed that NIFTP nodules with these variants had significant differences in chromatin condensation ( P = .0002).…”

The effects of the genetic polymorphisms of antioxidant enzymes on susceptibility to papillary thyroid carcinoma

“…21,22 A large number of studies have been carried out on candidate genes to illustrate the role of genetics in PTC development, but the findings show no similar results for a gene. 23,24 Despite the powerful effect of oxidative stress mechanisms on cancer susceptibility including PTC, a few gene variants have been investigated and inconsistent results have also been reported. 25 There are many polymorphisms in the antioxidant enzymes' genes which may alter their ROS detoxification efficiency.…”

The Role of Genetic Polymorphisms in Differentiated Thyroid Cancer: A 2023 Update

“…Moreover, the rs1042522 was associated with tumors > 1 cm in dominant and recessive models ( p = 0.04, p = 0.009, respectively) and with vascular invasion in the dominant model ( p = 0.01). However, regarding SNP of the p21 gene (rs10559234 and rs1801270), no correlation was found with the risk of PTC or clinical and histopathologic features [ 37 ]. There is little data in the literature concerning SNP in these genes and their role in thyroid cancer; therefore, there is a need to expand the research towards this area knowing the role they have in suppressing carcinogenesis.…”