The Role ofp73G4C14-to-A4T14 Polymorphism in the Susceptibility to Cervical Cancer

Abstract

Several reports have suggested the importance of p73 polymorphisms in tumor behavior. We investigated the role of a p73 gene polymorphism in the susceptibility to cervical lesions in a southwestern European population. Peripheral blood samples were obtained from Radiotherapy and Gynaecology Departments of Portuguese Institute of Oncology (Porto, Portugal), from 1998 to 2002. We analyzed the p73 cytosine thymine polymorphism in peripheral blood DNA of 176 healthy donors, 38 high-grade squamous intraepithelial lesions (HSIL), and 141 patients with primary untreated invasive cervical cancers (ICC), by polymerase chain reaction-restriction fragment length polymorphism. Our results demonstrate a twofold increased susceptibility to the development of HSIL in women carrying the p73 AT allele (OR=2.39; p=0.022). Further, this association seems to be more evident in women with high parity (OR=12.53; p=0.007). This is in agreement with the possible role of p73 in cervical carcinogenesis, namely, in human papillomavirus-infected transition zone subjected to the action of estrogens and in conjunction with disruption of differentiation program of this squamous epithelium that occurs in HSIL phase before the next step to invasiveness and squamous cervical cancer.

Association between the p73 gene G4C14-to-A4T14 single nucleotide polymorphism and risk of cervical cancer by high resolution melting and PCR with confronting two-pair primers in a Chinese population

“…Furthermore, a previous study observed that the AT variant was associated with significantly decreased risk of cervical cancer compared with p73 GC homozygotes (37). The results of the present study are consistent with Craveiro et al (35) and demonstrated that individuals carrying the p73 G4C14-to-A4T14 AT/AT genotype are associated with a higher risk of cervical cancer than individuals with the GC/GC genotype in a Chinese population. In addition, a significant association was observed between p73 G4C14-to-A4T14 SNP genotypes and tumor size in patients with cervical cancer (P=0.014; χ 2 =8.607).…”

“…However, the number of these studies is limited. It has been demonstrated that patients with cervical cancer carrying the p73 AT allele in a southwestern European population have a two-fold increased susceptibility of developing high-grade squamous intraepithelial lesions (35). By contrast, an unconditional logistic model performed risk estimation for each p73 genotype and identified a possible association between the p73 A4T14 variant and risk of cervical cancer in a Japanese population (P=0.053; OR = 1.57; 95% CI = 0.99-2.48) (36).…”

Role of the RAD51 G172T polymorphism in the clinical outcome of cervical cancer patients under concomitant chemoradiotherapy

“…Therefore, gene polymorphisms of DNA repair factors are therefore obvious candidates for determinants of repair capacity and chemotherapy efficacy (Sancar, 1995). Moreover, the functional variants caused by SNPs in genes encoding drugmetabolizing enzymes, transporters, ion channels, drug receptors, cell cycle proteins and DNA repair are known to be associated with individual variation in survival, drug responses, and toxicity (Henson et al, 2006;Costa et al, 2008;Nogueira et al, 2010;Catarino et al, 2008;Craveiro et al, 2012;Santos et al, 2006;Medeiros et al, 2003).…”

Role ofp73Dinucleotide Polymorphism in Prostate Cancer and p73 Protein Isoform Balance

“…However, other studies have reported a decreased risk in lung [29] and head and neck cancers [19]. In addition, many studies reported no association in breast [7, 9, 10], cervical [11], colorectal [13, 14, 16], endometrial [17], head and neck [13, 18, 19, 21, 22], gastric [13, 25], ovarian [36], melanoma [35], and lung [30, 31, 33] cancers (Table 4). Recent meta-analyses have shown that the p73 DNP is associated with various cancer risks in general [38–41].…”