Tumor Biol. DOI 10.1007/s13277-013-1518-0

RESEARCH ARTICLE

Genetic association between p53 codon 72 polymorphism and risk of cutaneous squamous cell carcinoma Ting Liu & Zeyuan Lei & ZhengYing Pan & Yu Chen & Xiang Li & TongChun Mao & Qian He & Dongli Fan

Received: 23 October 2013 / Accepted: 4 December 2013 # International Society of Oncology and BioMarkers (ISOBM) 2013

Abstract This study was designed to obtain a conclusive result about the relevance of p53 codon 72 polymorphism to the risk of cutaneous squamous cell carcinoma (SCC). We performed an updated meta-analysis of 3,792 subjects (1,349 cancer cases and 2,443 controls) to summarize the data available for p53 codon 72 polymorphism and SCC risk. The association was estimated by odds ratios (ORs) with 95 % confidence intervals (CIs). The meta-analysis showed no statistical significance for SCC risk associated with any of the genetic models of p53 codon 72 polymorphism. The analyses by ethnic subgroup also failed to produce significant associations. This study suggests that p53 codon 72 polymorphism does not appear to represent a significant susceptibility factor for SCC in Caucasians. Keywords p53 codon 72 . Polymorphism . SCC . Risk . Meta-analysis

Introduction Non-melanoma skin cancer (NMSC) has been a common cancer among humans, especially in Caucasians. The incidence ranks the first among all types of malignancies in this ethnicity [1]. NMSC has two subtypes including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) [2]. The former constitutes 80 % and the latter accounts for the rest [3]. Although the incidence of SCC is relatively lower compared to that of BCC, it has been a leading public health problem [4, 5]. Epidemiological studies have established Ting Liu and Zeyuan Lei are co-first authors. T. Liu : Z. Lei : Z. Pan : Y. Chen : X. Li : T. Mao : Q. He : D. Fan (*) Department of Plastic and Cosmetic Surgery, XinQiao Hospital, The Third Military Medical University, ChongQing 400037, China e-mail: [email protected]

several physical and chemical agents, such as exposure to ultraviolet (UV) rays, ionizing radiation, arsenic, psoralens and coal tar products, and immunosuppression [6, 7]. However, genetic polymorphisms are major contributing agents to SCC [8]. The importance of genetic polymorphisms in SCC risk has led to substantially increased research in this field, yet failing to facilitate a clear understanding of the etiology. The tumor suppressor gene p53 is essential for maintaining chromosomal integrity, and functional inactivation of this protein frequently occurs in various human cancers [9]. A common genomic polymorphism at codon 72 with a substitution of an arginine (Arg) to a proline (Pro) is involved in several different phenotypes including transcriptional activity [10] and apoptotic potential [11]. Many studies have investigated the role of p53 codon 72 polymorphism in a variety of cancers, such as prostate cancer [12], lung cancer [13, 14], bladder cancer [15], head and neck cancer [16], cervix cancer [17, 18], and non-melanoma skin cancer [19, 20]. Nevertheless, this polymorphism studied has not showed a clear association with cancer risk, particularly in SCC, thus producing a situation of conflicting conclusions [21–28]. Meta-analysis is a powerful way to identify the association of genetic polymorphisms with cancer risk. Based on the important role of p53 codon 72 polymorphism in skin carcinogenesis and the additional inconsistent results, we collected all available publications to date on p53 codon 72 polymorphism to obtain a conclusive result about its relevance in susceptibility to SCC.

Materials and methods Literature search We carried out a comprehensive search in PubMed, EMBASE, and Web of Science for genetic association studies

Tumor Biol.

concerning p53 codon 72 polymorphism and SCC risk without language restriction. The following keywords were used in this search: “p53 codon 72” or “p53 Arg72Pro,” “polymorphism” or “variants,” and “non-melanoma skin cancer” or “cutaneous squamous cell carcinoma.” We also reviewed the references of the extracted publications to retrieve data that we may have missed in the initial search.

analyses were performed with STATA 12.0 (StataCorp, College Station, TX, USA).

Inclusion criteria

A total of 31 articles regarding the association between p53 codon 72 polymorphism and SCC risk were extracted from the bibliography search. We excluded 21 studies that were not consistent with the inclusion criteria. Finally, ten studies with 1,349 cancer cases and 2,443 controls were included in this meta-analysis (Fig. 1). The key characteristics are summarized in Table 1. All studies were conducted in the subjects of Caucasian descent. In addition, among the ten studies, there were five hospital-based papers [20, 21, 23, 26, 28], three population-based studies [24, 25, 27], and two were defined as NA (not available) [19, 22], because it was not mentioned in the original article. The genotyping method contains the classic polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay, PCR, PCR-sequence specific primers, and TaqMan. The distribution of genotypes in the controls was all in agreement with HWE except two studies [19, 22].

We designed the following criteria for the eligible studies: (a) studies published before March 2013; (b) evaluation of p53 codon 72 polymorphism and SCC risk; (c) case–control studies in humans; and (d) studies with detailed genotyping frequencies. Data extraction Necessary data were independently extracted from the eligible studies by two investigators following the inclusion criteria listed above. The information that needed to be collected was as follows: first author's name, year of publication, country origin, ethnicity, source of control, genotyping methods, total number of cases, and controls and distribution of genotypes in cases and controls. In the event that a study included subpopulations and complete genotyping data, they were separated as different studies. Statistical methods The estimate of association between p53 codon 72 polymorphism and SCC risk was assessed by odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs). For p53 codon 72 polymorphism, the meta-analysis examined the association with SCC risk in the following five genetic models: Arg/Arg vs. Pro/Pro, Arg/Arg+Arg/Pro vs. Pro/Pro, Arg/Arg vs. Arg/Pro+Pro/Pro, allele Arg vs. allele Pro, and Arg/Pro vs. Pro/Pro. Subgroup analyses were performed by ethnicity and source of controls. Between-study heterogeneity was evaluated by the chisquare-based Q test [29] and P

Genetic association between p53 codon 72 polymorphism and risk of cutaneous squamous cell carcinoma.

This study was designed to obtain a conclusive result about the relevance of p53 codon 72 polymorphism to the risk of cutaneous squamous cell carcinom...
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