<b><i>TP53</i></b> Codon 72 and Intron 3 Polymorphisms and Mutational Status in Gastric Cancer: An Association with Tumor Onset and Prognosis

Abstract

Although TP53 alterations have been studied in human tumors, data considering the role of two common TP53 polymorphisms (Pro72Arg in codon 72 and Ins16bp in intron 3) and their associations with TP53 mutations in gastric cancer are very limited. Thus, we analyzed these parameters taking into consideration the clinicopathological data. DNA from 106 gastric tumor samples was available for TP53 Pro72Arg and TP53 Ins16bp polymorphism genotyping by PCR-RFLP and PCR, respectively. The mutational status of the TP53 exons 5–7 was assessed by the single-strand conformational polymorphism test. The TP53 72ArgArg genotype was statistically associated with patients aged ≥65 years (p = 0.039), and the intron 3 A2A2 genotype was correlated with late-stage tumors (III and IV; p = 0.043). Considering both polymorphisms, a negative correlation between the TP53 Pro-A1 haplotype and age <65 years (r = –0.211; p = 0.030) was found. Taking into account the TP53 mutations, the Pro/Pro genotype was positively correlated with the presence of exon 7 mutations (p = 0.049), and a correlation between this genotype and the number of mutations in TP53 was observed (p = 0.019). This study corroborates the understanding of TP53 polymorphisms in gastric carcinogenesis, especially regarding the genetic features in tumor onset and prognosis.

Identification of DNA mutations in gastric washes from gastric adenocarcinoma patients: Possible implications for liquid biopsies and patient follow‐up

“…Among these, TP53 has been reported as one of the most frequently mutated genes in GAC, with frequencies varying from 13% to 70% . The mutational rate of TP53 found in this study (32.6%) is similar to previous findings (38%, n = 138), (33%, n = 251) and (38.7%, n = 106), but discrepant to others, which found mutation rates of 50% ( n = 295), 59% ( n = 49) or 13% ( n = 277) . In GAC, TP53 mutations appear to play an important role in the early stages of carcinogenesis and have also been found in potentially malignant lesions, such as intestinal metaplasia, where the number of mutations seems to accumulate as the disease progresses .…”

Polymorphisms in eicosanoid‐related biosynthesis enzymes associated with acute urticaria/angioedema induced by nonsteroidal anti‐inflammatory drug hypersensitivity

“…Such regulation may also play a key role in the development of particular clinical phenotypes. Thus, intronic variants have been associated with different types of cancers, 46–49 cardiovascular diseases, 50,51 and autoimmune disorders such as systemic lupus erythematosus, Hashimoto thyroiditis and rheumatoid arthritis 52 . In fact, in 2019 we reported several variants in a guanine nucleotide binding protein to be associated with NIUA 20 .…”

Genetic Variants in Cytosolic Phospholipase A2 Associated With Nonsteroidal Anti-Inflammatory Drug–Induced Acute Urticaria/Angioedema

“…The development of specific clinical entities may be influenced by intron regulation. In this sense, introns have been linked to cardiovascular (Bose et al, 2017;Wang et al, 2019) and autoimmune diseases (AlFadhli, 2013) and cancer (Neves Filho et al, 2012;Blackburn et al, 2016;Tauziède-Espariat et al, 2017;Garinet et al, 2019). Deep-sequencing technologies have also highlighted the role of intronic mutations in human diseases through different molecular mechanisms (Vaz-Drago et al, 2017;Dufner-Almeida et al, 2019).…”