Genetic polymorphisms and cervical cancer development: ATM G5557A and p53bp1 C1236G

Abstract

Persistent infections by high-risk types of human papillomavirus (HPV) have been established as the etiological agent of cervical cancer. The integration of the HPV genome into the host genome is a crucial step in cervical carcinogenesis, although, correct activation of DNA damage repair pathways will avoid the development of cancer. Recent data indicate that several polymorphisms of key regulators from the DNA damage repair pathway (i.e. 53BP1 and ATM) are associated with cancer development susceptibility. We have developed a hospital-based retrospective study considering 429 cervical specimens from women with different cervical lesions including invasive carcinoma. This study aimed to evaluate the role of the ATM D1853N (5557G>A) and 53bp1 D353E (1236C>G) polymorphisms in the development of cervical cancer, using TaqMan® SNP Genotyping Assays. Statistical analysis revealed that ATM 5557GG homozygous individuals (OR=1.94; p=0.044) are at increased risk of developing LSIL, while for the 53BP1 1236C>G polymorphism no association was found. Nevertheless, we observed a tendency for an increased risk of LSIL in 53BP1 1236C allele carriers (OR=1.63; p=0.069). Logistic regression adjusted for age revealed no significant differences from the non-adjusted analysis. This is the first study to evaluate the role of ATM G5557A and P53BP1 C1236G polymorphisms in cervical cancer susceptibility. This study reveals a possible trend of both polymorphisms for a genetic susceptibility pattern of cervical cancer development. Hence, our results may be of interest for future understanding of the progression of cervical cancer.

Gene-environment interaction for polymorphisms in ataxia telangiectasia-mutated gene and radiation exposure in carcinogenesis: results from two literature-based meta-analyses of 27120 participants

“…A total of 29 studies were identified for the meta-analysis of individuals without radiation exposure [12, 17–44], and 6 studies for the meta-analysis of individuals with radiation exposure [11–16] (Figure 1). The ATM rs1801516 genotype distribution in controls was not in Hardy–Weinberg equilibrium (HWE) in 5 studies [12, 18–21], could not be assessed in 4 studies [11, 13, 25, 26], and was in HWE for the other studies [17, 22–24, 27–44]. As a result, 5 studies were identified with methodological errors and were excluded from a meta-analysis [12, 18–21].…”

“…The included studies had a relatively high quality with a median score of 7, ranging from 5 to 9. The quality was high for 22 studies (≥ 6) [11–16, 25, 26, 28–30, 32–40, 42, 43] and low for 8 studies (≤ 5) [17, 22–24, 27, 31, 41, 44]. …”

“…This meta-analysis included 24 studies with 9858 cases and 13475 controls [17, 22–44] (Table 1). When all cancer types were considered, there was no significant association of the rs1801516 polymorphism with cancer risk (homozygous model: odds ratio [OR] = 0.84, 95% confidence interval [CI]: 0.68, 1.03, P = 0.074; heterozygous model: OR = 0.99, 95%CI: 0.91, 1.07, P = 0.784; recessive model: OR = 0.87, 95%CI: 0.69, 1.10, P = 0.231; dominant model: OR = 0.97, 95%CI: 0.89, 1.06, P = 0.632).…”

Lack of Association of the TP53BP1 Glu353Asp Polymorphism with Risk of Cancer: A Systematic Review and Meta-Analysis

“…The SNPs for TP53BP1 gene may play an important role in the etiology of cancer because of a direct role of TP53BP1 in the cellular response to DNA damage. Previous researches have revealed that no association between TP53BP1 Asp353Glu (rs560191) SNPs and cancer risk [4]–[9], but Kiyohara et al reported that the Glu/Glu genotype of TP53BP1 Asp353Glu was associated with a decreased risk of lung cancer [10]. So the results of studies concerning association between Asp353Glu (rs560191) polymorphism in TP53BP1 gene and risk of cancer are conflicting.…”

The MBD4 Glu346Lys Polymorphism Is Associated With the Risk of Cervical Cancer in a Chinese Population

“…There are many polymorphisms in the DNA repair genes closely associated with the risk of cervical cancer. 10 Thus, we hypothesized that the polymorphisms in the MBD4 gene may have an impact on MBD4 expression or activity, and so they modulate the susceptibility to cervical cancer. Among the MBD4 polymorphisms identified, the Glu346Lys (rs140693, G9A) polymorphism in the MBD4 gene has been associated with susceptibility to several cancers.…”