TP53 Pro72 Allele Is Enriched in Oral Tongue Cancer and Frequently Mutated in Esophageal Cancer in India

Purpose

The tumor suppressor p53 is known to be inactivated frequently in various cancers. In addition, germline polymorphisms in TP53 are known to affect protein function and influence risk of developing different types of cancers. In this study, we analyzed the association of TP53 Pro72Arg polymorphism with squamous cell carcinoma of oral tongue (SCCOT) and esophagus (ESCC) in India.

Methods

We assessed the distribution of TP53 Pro72Arg polymorphism in one hundred and fifteen and eighty two SCCOT and ESCC patients, respectively, with respect to one hundred and ten healthy controls from the same population. In addition, we analyzed association of the polymorphism with several clinico-pathological and molecular parameters.

Results

Pro72 allele was significantly enriched in SCCOT patients compared to the healthy control group but neither allele was enriched in ESCC. Interestingly, Pro72 allele was preferentially mutated in ESCC which was confirmed by analysis of samples heterozygous for Pro72Arg.

Conclusions

Our study revealed the association of Pro72 allele with SCCOT suggesting the effect of this polymorphism on SCCOT risk. Preferential mutation of Pro72 allele exclusively in ESCC indicates the need for further studies to understand the tissue specific effect of p53 polymorphism.     

p53 codon 72 polymorphism and Hematological Cancer Risk: An Update Meta-Analysis

Background

Previous studies on the association of p53 codon 72 (Arg72Pro) polymorphism with hematological malignancies risk have produced conflicting results. The purpose of this meta-analysis is to define the effect of p53 Arg72Pro polymorphism on hematological malignancies risk.

Methodology/Principal Findings

Through searching PubMed databases (or hand searching) up to April 2012 using the following MeSH terms and keywords: “p53”, “codon 72” “polymorphism” and “leukemia”, or “lymphoma”, or “myeloma”, thirteen were identified as eligible articles in this meta-analysis for p53 Arg72Pro polymorphism (2,731 cases and 7, 356 controls), including nine studies on leukemia (1,266 cases and 4, 474 controls), three studies on lymphoma (1,359 cases and 2,652 controls), and one study on myeloma. The overall results suggested that p53 Arg72Pro polymorphism was not associated with hematological malignancies risk. In stratified analyses, significantly increased non-Hodgkin lymphomas risk was found in p53 Arg72Pro polymorphism heterozygote model (Arg/Pro vs. Arg/Arg: OR = 1.18, 95%CI: 1.02–1.35) and dominant model (Arg/Pro+Pro/Pro vs. Arg/Arg: OR = 1.18, 95%CI: 1.03–1.34), but no significant association was found between leukemia risk and p53 Arg72Pro polymorphism. Further studies showed no association between leukemia risk and p53 Arg72Pro polymorphism when stratified in subtypes of leukemias, ethnicities and sources of controls.

Conclusions/Significance

This meta-analysis indicates that the p53 Arg72Pro polymorphism may contribute to susceptibility to non-Hodgkin lymphomas.     

Arg72Pro Polymorphism of TP53 Gene and the Risk of Skin Cancer: a Meta-Analysis

Background

TP53 gene is one of the most important tumor suppressor genes. We undertook this meta-analysis to explore the association between TP53 Arg72Pro polymorphism and the risk of skin cancer mainly in Caucasians.

Methods

We searched PubMed for case-control studies published up to March 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.

Results

A total of 5276 skin cancer cases and 5315 controls from 20 studies were included. Overall, no significant association between TP53 Arg72Pro polymorphism and skin cancer was observed in all genetic contrast models (Pro/Pro versus Arg/Arg, Pro/Arg versus Arg/Arg, Pro/Pro + Pro/Arg versus Arg/Arg, Pro/Pro versus Arg/Arg + Pro/Arg, Pro allele versus Arg allele). Similar results were obtained in the stratified analysis by ethnicity and histological types of skin cancer, such as melanoma, squamous cell carcinoma and basal cell carcinoma. Power calculations indicated that some studies were underpowered. No publication bias was found by using the funnel plot and Egger''s test.

Conclusions

This meta-analysis indicated that TP53 Arg72Pro polymorphism probably had little association with skin cancer susceptibility mainly in Caucasians. However, larger sample-size studies are required to verify the conclusion as low statistical powers.     

Evaluating the Association between p53 Codon 72 Arg>Pro Polymorphism and Risk of Ovary Cancer: A Meta-Analysis

Aim

Allelic polymorphism in codon 72 of the p53 tumor suppressor gene causes imbalance of p53 protein expression. Earlier studies have shown association between allelic polymorphism in codon 72 of the p53 gene with risk of ovary cancer (OC); however the results are inconclusive and conflicting. Therefore, we performed this meta-analysis to investigate the relation between p53 codon 72 Arg>Pro polymorphism and overall OC susceptibility.

Methods

We searched all eligible published studies based on the association between codon 72 of the p53 Arg>Pro polymorphism and risk of OC. Data were pooled together from individual studies and meta-analysis was performed. Pooled odds ratios (ORs) and 95% CI were calculated for allele contrast, homozygous, heterozygous, dominant and recessive genetic models.

Results

A total of twelve studies comprising of 993 OC cases and 1264 healthy controls were included in this meta-analysis. Overall, no significant association was detected for Pro allele carrier (Pro vs. Arg: p = 0.916; OR = 0.980, 95% CI = 0.677 to 1.419), homozygous (Pro/Pro vs. Arg/Arg: p = 0.419; OR = 0.731, 95% CI = 0.341 to 1.564), heterozygous (Arg/Pro vs. Arg/Arg: p = 0.248; OR = 1.237, 95% CI = 0.862 to 1.773), dominant (Pro/Pro+Arg/Pro vsArg/Arg: p = 0.699; OR = 1.089, 95% CI = 0.706 to 1.681), and recessive (Pro/Pro vs Arg/Arg+Arg/Pro: p = 0.329; OR = 0.754, 95% CI = 0.428 to 1.329) genetic models, respectively. Also, in the stratified analysis by ethnicity, no significant association of this polymorphism with risk of OC was found in the Caucasian population.

Conclusions

This meta-analysis suggested that codon 72 of the p53 Arg>Pro polymorphism may not significantly contribute in ovary cancer susceptibility. However, future large studies with gene-gene and gene-environment interactions are needed to validate these findings.     

Assessment of changes in the brca2 and p53 genes in breast invasive ductal carcinoma in northeast Brazil

Background

BRCA protein interacts with at least 13 different proteins that have been implicated with cancer susceptibility and loss of BRCA function is correlated to sensitivity to DNA crosslinking agents in preclinical models.

Results

BRCA2 methylation frequency was 44%, p53 Pro22 allele frequency was 32% and heterozygous frequency of Arg/Pro72 genotype was 60% which could be associated as risk factor for metastasis (p = 0.046 OR = 4.190). Regarding to polymorphism of codon 249 the frequency of Arg249 allele presented 82% which was considered not statistically significant.

Conclusions

There was not statistical significance to BRCA2 promoter methylation with any parameters chosen. However, our findings suggest that patients who present heterozygous genotype at codon 72 of p53 gene may have a major susceptibility to any type of metastasis and this could serve as potential auxiliary biomarker for poor prognosis.     

Increased Risk of Cutaneous Melanoma Associated with p53 Arg72Pro Polymorphism

Objective

The objective of this study was to test the hypothesis that p53 Arg72Pro polymorphism may contribute to an increased risk of cutaneous melanoma (CM).

Methods

By searching the databases of PubMed, EMBASE, and Web of Science, a total of 8 eligible case-control studies with 1,957 CM cases and 2,887 controls were included in this meta-analysis. Stata software was used to analyze all the statistical data.

Results

The pooled data by a fixed-effects model suggested an increased risk of CM associated with p53 Arg72Pro polymorphism under the genetic model of Arg/Pro vs. Pro/Pro without heterogeneity (OR_{Arg/Pro vs. Pro/Pro} = 1.76, 95% CI = 1.55-1.99, P _{heterogeneity} = 0.075). A similar trend was seen in subgroups of hospital-based studies and population-based studies.

Conclusion

Our meta-analysis based on all studies shows that the p53 Arg72Pro polymorphism may increase individual susceptibility to CM, particularly in Caucasians and could serve as a biomarker to predict the population at high risk of CM.     

Quantitative assessment of the association between TP53 Arg72Pro polymorphism and bladder cancer risk

Previous studies investigating the association between TP53 Arg72Pro polymorphism and bladder cancer risk reported controversial results. To quantify the strength of association between TP53 Arg72Pro polymorphism and bladder cancer risk, we performed this meta-analysis. We searched PubMed, Embase and Wangfang databases for studies relating the association between TP53 Arg72Pro polymorphism and bladder cancer risk. We used the pooled odds ratios (ORs) with their 95 % confidence intervals (95 % CIs) to assess the association. Finally, data were available from a total of 16 case–control studies including a total of 5, 545 subjects (2,345 cases and 3,200 controls). Meta-analysis of all 16 studies showed TP53 Arg72Pro polymorphism was not associated with bladder cancer risk (All P values were more than 0.10). Subgroup analyses by ethnicity showed that TP53 Arg72Pro polymorphism contributed to bladder cancer risk in East Asians in three genetic models (For Pro vs. Arg, Fixed-effects OR 1.18, 95 % CI 1.05–1.32; For ProPro vs. ArgArg, Fixed-effects OR 1.40, 95 % CI 1.11–1.77; For ProPro vs. ArgPro/ArgArg, Fixed-effects OR 1.32, 95 % CI 1.07–1.62). However, there was no significant association in Caucasians and the others (All P values were more than 0.05). Heterogeneity analyses suggested ethnicity was the major sources of heterogeneity. Thus, meta-analyses of available data suggest the Pro variant of TP53 Arg72Pro contributes to bladder cancer risk in East Asians. Besides, TP53 Arg72Pro polymorphism may have race-specific effects on bladder cancer risk and further studies are needed to elucidate this possible effect.     

The Functional TP53 rs1042522 and MDM4 rs4245739 Genetic Variants Contribute to Non-Hodgkin Lymphoma Risk

As a heterogeneous kind of malignances, Non-Hodgkin lymphoma (NHL) is the most common hematologic cancer worldwide with the significantly increased morbidity in China. Accumulated evidences demonstrated that oncoprotein MDM4 plays a crucial role in the TP53 tumor suppressor signaling pathway. An rs4245739 A>C polymorphism locating in the MDM4 3′-untranslated region creates a miR-191 target site and results in allele-specific MDM4 expression. In this study, we examined the association between this polymorphism as well as the TP53 Arg72Pro (rs1042522 G>C) genetic variant and Non-Hodgkin Lymphoma (NHL) risk in a Chinese Han population. Genotypes were determined in 200 NHL cases and 400 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found significantly increased NHL risk among carriers of the TP53 72Pro allele compared with those with the 72Arg allele (P = 0.002 for the Pro/Pro genotype). We also observed a significantly decreased NHL risks among carriers of the MDM4 rs4245739 C allele compared with those with the A allele in Chinese (P = 0.014 for the AC genotype). Stratified analyses revealed the associations between these SNPs and NHL risk are especially noteworthy in young or male individuals. Additionally, the associations are much pronounced in NHL patients with B-cell lymphomas or grade 3 or 4 disease. Our results indicate that the TP53 Arg72Pro and the MDM4 rs4245739 polymorphisms contribute to NHL susceptibility and support the hypothesis that genetic variants in the TP53 pathway genes can act as important modifiers of NHL risk.     

Association of p53 Arg72Pro polymorphism with gastric cancer: a meta-analysis

Background: p53 tumor suppressor gene Arg72Pro polymorphism has been associated with gastric cancer. However, results were inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and gastric cancer.

Methods: An electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and the association was assess by pooled odds ratio (ORs) with 95% confidence interval (CIs).

Results: The meta-analysis suggested that the p53 Arg72Pro was associated with the gastric cancer risk (Additive model: OR = 1.149, 95% CI = 1.045–1.263, p = 0.004; Dominant model: OR = 1.18, 95% CI = 1.049–1.328, p = 0.006; Recessive model: OR = 1.202, 95% CI = 1.013–1.427, p = 0.035) in Asian subgroup.

Conclusion: This meta-analysis suggests that p53 Arg72Pro polymorphism is associated with increased risk of gastric cancer in Asians.     

Promoter polymorphisms of pri-miR-34b/c are associated with hepatocellular carcinoma

Background

Numerous studies have focused on the association between miR-34 family members, which are direct p53 targets, and carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). This study aimed to assess whether polymorphisms in the single-nucleotide polymorphism miR-34b/c T>C (rs4938723) and TP53 Arg72Pro (rs1042522) increase the risk of HCC and influence outcome in patients with HCC.

Patients and methods

We enrolled 157 HCC patients and 201 cancer-free control subjects from the Korean population. MicroRNA polymorphisms were genotyped using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method.

Results

We found that the miR-34b/c TC + CC frequency was significantly higher in HCC patients than in controls (adjusted odds ratio [AOR]: 1.580; 95% confidence interval [CI]: 1.029–2.426). The miR-34b/c CC-TP53 Arg/Arg combination significantly increased the risk of HCC (AOR: 13.644; 95% CI: 1.451–128.301). The SNPs miR-34b/c T>C and TP53 Arg72Pro(G>C) had no influence on survival of HCC patients.

Conclusions

Our findings suggest that loss of the T allele in miR-34b/c T>C, and the miR-34b/c CC-TP53 Arg/Arg combination increases the risk of HCC in the Korean population.     

Meta-analysis demonstrates no association between p53 codon 72 polymorphism and prostate cancer risk

We examined whether p53 codon 72 polymorphism confers prostate cancer risk by conducting a meta-analysis. Two investigators independently searched the Pubmed, Embase and CBM databases. This meta-analysis was made of seven case-control studies, that included 892 prostate cancer cases and 1020 healthy controls. Meta-analysis results based on all the studies showed no significant association between p53 codon 72 polymorphism and prostate cancer risk in the comparisons of Pro allele vs Arg allele; Pro/Pro + Pro/Arg vs Arg/Arg; Pro/Pro vs Pro/Arg + Arg/Arg; Pro/Pro vs Arg/Arg, and Pro/Arg vs Arg/Arg [odds ratio (OR) = 1.09, 95% confidence interval (CI) = 0.87-1.36, P = 0.47; OR = 1.22, 95%CI = 0.86-1.73, P = 0.27; OR = 1.03, 95%CI = 0.62-1.72, P = 0.91; OR = 1.22, 95%CI = 0.66-2.26, P = 0.52; OR = 1.25, 95%CI = 0.84-1.87, P = 0.27, respectively]. In the subgroup analysis by ethnicity, no association was found between p53 codon 72 polymorphism and prostate cancer risk both in Caucasian and Asian populations. We found no association between p53 codon 72 polymorphism and prostate cancer risk.     

Meta-analysis of an association of codon 72 polymorphisms of the p53 gene with increased endometrial cancer risk

Polymorphisms of the p53 gene have been associated with susceptibility to endometrial cancer. However, whether there is a specific association is still controversial. We investigated a possible association between p53 codon 72 polymorphism and endometrial cancer risk by conducting a meta-analysis. Publications addressing this association were selected from the Pubmed, Embase and CBM databases (up to January 2011). Data were extracted from the studies by two independent reviewers. The meta-analysis was performed using RevMan 5.0.25 and STATA 9.2 softwares. The odds ratio (OR) with 95% confidence intervals (CI) was calculated. Then, 10 case-control studies were retrieved, with a total of 917 endometrial cancer patients and 1680 healthy controls. Meta-analysis results showed that the Pro allele and Pro carrier (Arg/Pro + Pro/Pro) of p53 codon 72 polymorphism were significantly related with endometrial cancer risk (OR = 1.25, 95%CI = 1.10-1.41, P = 0.0005; OR = 1.34, 95%CI = 1.12-1.59, P = 0.001, respectively). In the subgroup analysis, based on ethnicity, studies were divided into Asian and Caucasian populations; the Pro allele and Pro carrier (Arg/Pro + Pro/Pro) of p53 codon 72 polymorphism were significantly related with endometrial cancer risk in Asian populations (OR = 1.41, 95%CI = 1.19-1.66, P < 0.0001; OR = 1.66, 95%CI = 1.30-2.13, P < 0.0001, respectively), but not in Caucasian populations (both P > 0.05). We concluded that the Pro allele (Arg/Pro + Pro/Pro) of p53 codon 72 polymorphism is a potential risk factor for endometrial cancer.     

A p53 codon 72 polymorphism associated with prostate cancer development and progression in Japanese

An association between the Pro/Pro genotype of p53 codon 72 and a lower risk of prostate cancer in Caucasians was recently reported. However, the association of this polymorphism with prostate cancer risk in a Japanese population has not been clarified. We performed a case-control study consisting of 114 prostate cancer patients and 105 noncancer controls. Sixty-nine percent (79 of 114) of the patients had a positive family history. The genotypic frequencies in the controls were 39.0% for Arg/Arg, 54.3% for Arg/Pro and 6.7% for Pro/Pro; they were in Hardy-Weinberg equilibrium. When a comparison of the distribution of the p53 codon 72 polymorphism was made between patients with a first-degree family history and all control subjects, the adjusted odds ratios (ORs) for prostate cancer associated with the Arg/Arg, Arg/Pro and Pro/Pro genotypes were 1.00, 0.99 [95% confidence interval (CI) 0.53-1.88] and 2.80 (95% CI 1.04-7.53), respectively. When stratification of cases was performed based on clinical stage (localized or metastatic cancer) and pathological grade (a Gleason score of <7 or > or =7), there tended to be a greater number of patients with localized cancers among those patients with the Arg/Pro genotype than among those with the Arg/Arg genotype (overall cases: age-adjusted OR 0.36, 95% CI 0.13-1.00, p = 0.049; positive family history cases: age-adjusted OR 0.25, 95% CI 0.075-0.84, p = 0.025). In addition, there tended to be a greater number of patients with low-grade cancers among those with the Pro/Pro genotype than among those with other genotypes (overall cases: age-adjusted OR 0.41, 95% CI 0.13-1.30, p = 0.13; positive family history cases: age-adjusted OR 0.20, 95% CI 0.004-0.89, p = 0.035). The present findings suggest that the Pro/Pro genotype of p53 codon 72 played a role in prostate cancer susceptibility in a Japanese population. However, the Pro allele did not appear to worsen such clinical parameters as clinical stage or pathological grade.     

TP53 codon 72 and intron 3 polymorphisms and mutational status in gastric cancer: an association with tumor onset and prognosis

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.     

Meta-analysis shows significant association of the <Emphasis Type="Italic">TP53</Emphasis> Arg72Pro with ovarian cancer risk

Growing bodies of studies have been conducted on the association of TP53 Arg72Pro polymorphism with susceptibility to ovarian cancer and have yielded conflicting results. Thus, a meta-analysis was performed to summarize the possible association. 18 case–control studies, including 2,193 ovarian cancer cases and 5,175 controls were identified. The quality of the studies was assessed according to a predefined scale. The strength of the associations between TP53 Arg72Pro polymorphism and ovarian cancer was measured by crude odds ratios (ORs) with 95% confidence intervals (CIs). Overall, no significant association was found between TP53 Arg72Pro polymorphism and ovarian cancer risk when all studies pooled into the meta-analysis in all genetic model. In the subgroup analysis by ethnicity, still no association of this polymorphism with ovarian cancer risk was obtained for all comparison models. However, significantly decreased risks of ovarian cancer were found for Arg/Arg versus Arg/Pro+Pro/Pro (OR 0.84, 95% CI 0.74–0.96) when the analysis was restricted to high quality studies. Conversely, when it was restricted to low quality studies, significantly increased risks were observed for Arg/Arg versus Pro/Pro (OR 1.58, 95% CI 1.09–2.28) and Arg/Arg+Arg/Pro versus Pro/Pro: (OR 1.50, 95% CI 1.10–2.06), which might be spurious due to the poor design of these studies. In conclusion, this meta-analysis suggests that the Arg allele is at a moderately reduced risk for ovarian cancer and this polymorphism might protect against ovarian carcinogenesis.     

The p53 Codon 72 PRO/PRO Genotype May Be Associated with Initial Central Visual Field Defects in Caucasians with Primary Open Angle Glaucoma

Background

Loss of vision in glaucoma is due to apoptotic retinal ganglion cell loss. While p53 modulates apoptosis, gene association studies between p53 variants and glaucoma have been inconsistent. In this study we evaluate the association between a p53 variant functionally known to influence apoptosis (codon 72 Pro/Arg) and the subset of primary open angle glaucoma (POAG) patients with early loss of central visual field.

Methods

Genotypes for the p53 codon 72 polymorphism (Pro/Arg) were obtained for 264 POAG patients and 400 controls from the U.S. and in replication studies for 308 POAG patients and 178 controls from Australia (GIST). The glaucoma patients were divided into two groups according to location of initial visual field defect (either paracentral or peripheral). All cases and controls were Caucasian with European ancestry.

Results

The p53-PRO/PRO genotype was more frequent in the U.S. POAG patients with early visual field defects in the paracentral regions compared with those in the peripheral regions or control group (p = 2.7×10⁻⁵). We replicated this finding in the GIST cohort (p  = 7.3×10⁻³, and in the pooled sample (p = 6.6×10⁻⁷) and in a meta-analysis of both the US and GIST datasets (1.3×10⁻⁶, OR 2.17 (1.58–2.98 for the PRO allele).

Conclusions

These results suggest that the p53 codon 72 PRO/PRO genotype is potentially associated with early paracentral visual field defects in primary open-angle glaucoma patients.     

Influence of Arg72Pro polymorphisms of TP53 on the response of buccal cells to radiotherapy

Polymorphisms in the TP53 gene codon 72 (Arg72Pro) influence apoptosis induction and DNA damage repair. We evaluated how variants of protein p53 (p53Arg and p53Pro) affect cell death and DNA damage repair by analyzing the frequencies of karyorrhexis and micronuclei. There were significant differences in the frequency of karyorrhexis between the three p53 genotypes (Arg/Arg, Arg/Pro, and Pro/Pro), between samples taken before and after radiotherapy, and between patients and controls. The frequency of micronucleated cells increased significantly after radiotherapy. There were no significant differences in the micronucleus frequency in healthy tissues of these patients compared to controls, or in the comparisons between the three genotypes. We conclude that Arg72Pro polymorphism influences cell apoptotic capacity. This is the first study investigating karyorrhexis and micronuclei, as indicators of apoptosis after radiotherapy, and how these indicators are influenced by the TP53 polymorphism Arg72Pro.     

湖南地区汉族人群p53 基因第72 位密码子多态性与宫颈鳞癌的相关性

目的:探讨宫颈组织p53基因第72位密码子的多态性及分析第72位密码子的多态性与湖南地区汉族人群宫颈鳞癌的相关性。方法:采用PCR方法扩增101例正常宫颈和150例宫颈鳞癌石蜡组织p53基因第72位密码子基因,回收目的片段进行测序。采用SPSS 11.5软件分析p53基因第72位密码子的多态性。结果:p53第72位密码子基因测序结果显示,在宫颈鳞癌组织中Arg/Arg、Pro/Pro、Arg/Pro所占比例分别为40.66%、16.67%、42.67%;在正常宫颈组织中Arg/Arg、Pro/Pro、Arg/Pro所占比例分别为47.53%、7.92%、44.55%。统计学分析结果显示,Arg/Arg和Arg/Pro基因型在宫颈鳞癌和对照组中的表达差异没有统计学意义(P>0.05);Pro/Pro基因型在宫颈鳞癌组中所占比例显著高于正常宫颈组织(P<0.05)。结论:p53基因第72位密码子Pro/pro基因型是湖南地区女性发生宫颈鳞癌易感因素。     

湖南地区汉族人群p53基因第72位密码子多态性与宫颈鳞癌的相关性

目的：探讨宫颈组织p53基因第72位密码子的多态性及分析第72位密码子的多态性与湖南地区汉族人群宫颈鳞癌的相关性。方法：采用PCR方法扩增101例正常宫颈和150例宫颈鳞癌石蜡组织p53基因第72位密码子基因,回收目的片段进行测序。采用SPSS11．5软件分析p53基因第72位密码子的多态性。结果：p53第72位密码子基因测序结果显示,在宫颈鳞癌组织中Arg／Arg、Pro／Pro、Arg／Pro所占比例分别为40．66％、16．67％、42．67％;在正常宫颈组织中Arg／Arg、Pro／Pro、Arg／Pro所占比例分别为47．53％、7．92％、44．55％。统计学分析结果显示,Arg／Arg和Arg／Pro基因型在宫颈鳞癌和对照组中的表达差异没有统计学意义（P〉0．05）;Pro／Pro基因型在宫颈鳞癌组中所占比例显著高于正常宫颈组织（P〈0．05）。结论：p53基因第72位密码子Pro／pro基因型是湖南地区女性发生宫颈鳞癌易感因素。     

Association of p53 Arg72Pro polymorphism with bladder cancer: A meta-analysis

Background

p53 tumor suppressor gene Arg72Pro polymorphism has been associated with bladder cancer. However, results were inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and bladder cancer.

Methods

Electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association.

Results

The final meta-analysis included 14 published studies with 2176 bladder cancer cases and 2798 controls. The results suggested that the variant genotype was associated with the bladder cancer risk (additive model: OR = 1.72, 95% CI: 1.036–1.325, P = 0.011; dominant model: OR = 1.268, 95% CI: 1.003–1.602, P = 0.047) in Asian subgroup. However, the association was not significant between this polymorphism and bladder cancer risk in Caucasian (additive model: OR = 0.773, 95% CI: 0.564–1.059, P = 0.109; dominant model: OR = 0.685, 95% CI: 0.418–1.124, P = 0.134).

Conclusion

This meta-analysis suggests that p53 Arg72Pro polymorphism is associated with increased risk of bladder cancer in Asians. To validate the association between this polymorphism and bladder cancer, further studies with larger participants worldwide are needed.