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.     

TP53 codon 72 polymorphism in pigmentary phenotypes

The p53 protein exerts different cellular functions, and recent findings have demonstrated its influence on the cascade of skin pigmentation during UV exposure. Among TP53 gene polymorphisms, the most studied is the G to C transversion in exon 4 at codon 72, which results in three distinct genotypes, Arg/Arg, Pro/Pro and Arg/Pro, each one encoding different p53 isoforms. Therefore, this study aimed to determine the relationship between TP53 codon 72 polymorphism and skin protection against sunburn. Genomic DNA was extracted from peripheral blood samples and genotyping was performed by PCR and confirmed by restriction enzyme digestion. The genotype frequency was 50% for Arg/Arg and 14.6% for Pro/Pro genotype. The frequency of heterozygous subjects was 35.4%. In our population, p53 genotypes were in Hardy-Weinberg (HW) equilibrium (X2 HM less than 3.84), showing a predominance of arginine allele (total Arg allele frequency of 68%). No significant association between p53 genotype and skin colour, hair or eye colour and susceptibility to sun exposure was found. However, further analysis demonstrated a significant association between the genotype Pro/Pro and blue/green eyes among participants who presented redness (P=0.016). Our findings indicate susceptibility to sun exposure when this phenotype (eye colour) occurs simultaneously with Pro/Pro genotype.     

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.     

Meta-analysis demonstrates association between Arg72Pro polymorphism in the P53 gene and susceptibility to keloids in the Chinese population

Although there is evidence suggesting genetic susceptibility for keloids, studies investigating the association between Arg72Pro polymorphism in the P53 gene and tendency to form keloids have given variable results. We made a meta-analysis of the effects of P53 Arg72Pro polymorphism on keloid risk in the Chinese population by conducting searches of the published literature in Pubmed, Embase, CBMdisc, and CNKI databases up to June 2011. Six studies were included in the meta-analysis, with a total of 359 keloid cases and 493 healthy controls. Meta-analysis results, respectively in the PCR-reverse dot blot and PCR-RFLP subgroups, showed significant associations between P53 Arg72Pro polymorphism and susceptibility to keloid in the comparisons of Pro allele vs Arg allele (odds ratio (OR) = 2.29, 95% confidence interval (CI) = 1.45-3.60; OR = 0.74, 95%CI = 0.56-0.98); Pro/Pro vs Pro/Arg + Arg/Arg (OR = 2.91, 95%CI = 1.88-4.53; OR = 0.54, 95%CI = 0.32-0.92); Pro/Pro vs Arg/Arg (OR = 2.79, 95%CI = 1.54-5.06; OR = 0.51, 95%CI = 0.28-0.92); Pro/Pro vs Pro/Arg (OR = 2.85, 95%CI = 1.75-4.63; OR = 0.57, 95%CI = 0.32-0.99). We conclude that the Pro allele of P53 Arg72Pro polymorphism is a risk factor for keloids in the Chinese population.     

P53 codon 11, 72, and 248 gene polymorphisms in endometriosis

OBJECTIVE: Mutated p53 gene is related to the instability of cell growth and cell cycle progression. We aimed to evaluate the association between endometriosis and p53 codon 11, 72 and 248 gene polymorphisms.PATIENTS AND METHODS: Women were divided into two groups: (1) moderate/severe endometriosis (n=148), and (2) non-endometriosis groups (n=150). P53 gene polymorphisms include codon11 Glu/Gln or Lys (GAG->CAG or AAG), codon 72 Arg/Pro (CGC->CCC), and codon 248 Arg/Thr (CGG->TCG). These gene polymorphisms were amplified by polymerase chain reaction and detected by electrophoresis after restriction enzyme (Taq I, BstU I, Hap II) digestions. Associations between the endometriosis and p53 polymorphisms were evaluated.RESULTS: The distributions of p53 codon 72 polymorphisms in both groups were significantly different. The proportions of Arg homozygotes/heterozygotes/Pro homozygotes in both groups were 9.5/66.2/24.3% and 30.7/50/19.3%. The proportions of Arg/Pro alleles were 42.6/57.4% and 56/44%. The distributions of p53 codon 11 and 248 polymorphisms in both groups were non-significantly different. All individuals appeared the wild genotypes (Glu11 and Arg248 homozygotes).CONCLUSION: Association between endometriosis and p53 codon 72 polymorphism exists. P53 codon 72*Pro-related genotype and allele are related with higher susceptibility of endometriosis. P53 codon 11 and 248 polymorphisms are not related with endometriosis susceptibility.     

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 associations of p53 overexpression with p53 codon 72 genetic polymorphism in esophageal cancer

Variations in p53 codon 72 have been identified as significant predisposing factors for various cancers, but molecular mechanisms remain unclear. We investigated associations of p53 overexpression with codon 72 variants and other factors with esophageal cancer. Status of p53 overexpression was determined by immunohistochemical staining. Codon 72 polymorphisms and mutation of p53 was identified by PCR-RFLP and direct sequencing from exons 4 to 9, respectively. We evaluated 126 patients who underwent esophagectomy in the National Taiwan University Hospital, and found that the status of p53 overexpression was significantly influenced by presence of codon 72 polymorphisms. After adjustment for other possible confounders, the incidence of p53 overexpression was significantly decreased in patients with Pro/Pro genotype with an odds ratio (OR) of 0.21 (95% CI: 0.067-0.64) (p = 0.0065) compared with incidence in patients with Arg/Arg genotype. The incidence of p53 overexpression was additively increased with environmental exposure to cigarette smoke, alcohol, and areca quid. When compared with individuals exposed to only one of these environmental risk factors, patients who had exposure to two or three risk factors had ORs of 6.11 (95% CI: 1.80-20.75) and 6.22 (95% CI: 1.81-21.34) for p53 overexpression, respectively. Elderly patients (age >70 years) were also more likely to have p53 overexpression, with an OR of 5.63 (95% CI: 1.53-20.64) compared with overexpression among patients aged less than 55 years. Forty-one patients received further evaluation of p53 mutation. There was also a higher incidence of, but without reaching a statistical significance, p53 mutation in patients with p53 overexpression (OR[95% CI]: 2.18 [0.52-9.6]) and codon 72 Arg/Arg genotype (OR [95% CI] of 0.8 [0.13-4.2], comparing genotypes of Pro/Pro and Arg/Pro with Arg/Arg). Our data provide the first observations that the presence of p53 codon 72 variants can be a significant factor influencing p53 overexpression in esophageal cancer, with overexpression also influenced by combined or prolonged environmental exposures.     

p53 codon 72 polymorphism is associated with susceptibility to hepatocellular carcinoma in the Turkish population: a case–control study

The tumor suppressor p53 gene plays a crucial role in preventing carcinogenesis through its ability to induce cell cycle arrest and apoptosis following DNA damage and oncogene activation. A guanine (G)/cytosine (C) common single nucleotide polymorphism (SNP) at second position of codon 72 in exon 4 of p53 gene determines a arginine (Arg) to proline (Pro) (Arg72Pro) aminoacidic substitution within the proline-rich domain of p53 protein. Arg72 and Pro72 allele are different from a biochemical and biological point of view and many reports suggest that they can modulate individual cancer susceptibility. To determine the association of the p53 Arg72Pro polymorphism with the risk of hepatocellular carcinoma (HCC) development in a Turkish population, a hospital-based case–control study was designed consisting of 119 subjects with HCC and 119 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the p53 Arg72Pro polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our data shows that the Pro/Pro genotype of the p53 Arg72Pro polymorphism is associated with increased risk of HCC development in this Turkish population (OR = 3.20, 95% CI: 1.24–8.22, P = 0.02). Furthermore, according to stratified analysis, a significant association was observed between the homozygote Pro/Pro genotype and HCC risk in the subgroups of male gender (OR = 3.01, 95% CI: 1.14–7.97, P = 0.03) and patients with hepatitis B virus (HBV)-related HCC (OR = 4.04, 95% CI: 1.46–11.15, P = 0.007). Because our results suggest for the first time that the Pro/Pro homozygote of p53 Arg72Pro polymorphism may be a genetic susceptibility factor for HCC (especially in the male gender and HBV-infected patients) in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.     

P53 polymorphism and lung cancer susceptibility: a pooled analysis of 32 case–control studies

To explore the real association between p53 codon 72 polymorphism and lung cancer risk, a pooled analysis of 32 case–control studies involving 19,255 subjects was conducted. When all 32 studies were pooled into the analysis, significantly elevated lung cancer risks were associated with variant genotypes in all genetic models (for Pro/Arg vs. Arg/Arg: OR 1.21, 95% CI 1.01–1.23; for Pro/Pro vs. Arg/Arg: OR 1.20, 95% CI 1.03–1.39; for Pro/Pro + Pro/Arg vs. Arg/Arg: OR 1.14, 95% CI 1.03–1.25; for Pro/Pro vs. Arg/Arg + Pro/Arg: OR 1.06, 95% CI 1.01–1.12). In the subgroup analysis by ethnicity, histological type, or smoking status, significantly increased risks were found in subgroups such as Asians, Caucasians, lung adenocarcinoma patients, or smokers, respectively. In conclusion, our results suggest that the Pro allele at p53 codon 72 is emerging as a low-penetrance susceptibility allele for lung cancer development.     

Investigation on the role of p53 codon 72 polymorphism and interactions with tobacco, betel quid, and alcohol in susceptibility to cancers in a high-risk population from North East India

The association of TP53 codon 72 polymorphism with cancer susceptibility remains uncertain and varies with ethnicity. Northeast India represents a geographically, culturally, and ethnically isolated population. The area reports high rate of tobacco usage in a variety of ways of consumption, compared with the rest of Indian population. A total of 411 cancer patients (161 lung, 134 gastric, and 116 oral) and 282 normal controls from the ethnic population were analyzed for p53 codon 72 polymorphism by polymerase chain reaction-restriction fragment length polymorphism. No significant difference in genotypic distribution of p53 between cases and controls was observed. Results suggested betel quid chewing as a major risk factor for all the three cancers (odds ratio [OR]=3.54, confidence interval [CI]=2.01-6.25, p<0.001; OR=1.74, CI=1.04-2.92, p=0.03; and OR=1.85, CI=1.02-3.33, p=0.04 for lung, gastric, and oral cancers, respectively). Tobacco smoking was associated with risk of lung and oral cancers (OR=1.88, CI=1.11-3.19, p=0.01 and OR=1.68, CI=1.00-2.81, p=0.04). Interactions between p53 genotypes and risk factors were analyzed to look for gene-environment interactions. Interaction of smoking and p53 genotype was significant only for oral cancer. Interactions of betel quid with p53 genotypes in lung cancer showed significant increase for all the three genotypes, indicating a major role of betel quid (OR=5.90, CI=1.67-20.81, p=0.006; OR=5.44, CI=1.67-17.75, p=0.005; and OR=5.84, CI=1.70-19.97, p=0.005 for Arg/Arg, Arg/Pro, and Pro/Pro, respectively). In conclusion, high incidence of these cancers in northeast India might be an outcome of risk habits; further, tissue- and carcinogen-specific risk modification by p53 gene is probable.     

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。     

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.     

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。     

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.     

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.     

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.     

The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death

A common arginine to proline polymorphism is harboured at codon 72 of the human p53 gene. In this investigation, we found that fibroblasts and lymphocytes isolated from arginine allele homozygote centenarians and sexagenarians (Arg+) undergo an oxidative-stress-induced apoptosis at a higher extent than cells obtained from proline allele carriers (Pro+). At variance, the difference in apoptosis susceptibility between Arg+ and Pro+ is not significant when cells from 30-year-old people are studied. Further, we found that Arg+ and Pro+ cells from centenarians differ in the constitutive levels of p53 protein and p53/MDM2 complex, as well as in the levels of oxidative stress-induced p53/Bcl-xL complex and mitochondria-localised p53. Consistently, all these differences are less evident in cells from 30-year-old people. Finally, we investigated the in vivo functional relevance of the p53 codon 72 genotype in a group of old patients (66-99 years of age) affected by acute myocardial ischaemia, a clinical condition in which in vivo cell death occurs. We found that Arg+ patients show increased levels of Troponin I and CK-MB, two serum markers that correlate with the extent of the ischaemic damage in comparison to Pro+ patients. In conclusion, these data suggest that p53 codon 72 polymorphism contributes to a genetically determined variability in apoptotic susceptibility among old people, which has a potentially relevant role in the context of an age-related pathologic condition, such as myocardial ischaemia.     

Association of XRCC1 Arg399GIn and Tp53 Arg72Pro polymorphisms and increased risk of uterine leiomyoma - A case-control study

The aim of present study was to investigate the role of the X-ray repair cross-complementing protein1 (XRCC1) and Tumor protein p53 (Tp53) polymorphisms in Uterine Leiomyoma (UL) susceptibility in southeastern Iran. This case control study was performed on 139 women with UL and 149 age, BMI and ethnicity matched healthy women. All women were genotyped for the XRCC1 Arg399Gln, XRCC1 Arg194Trp and Tp53 Arg72Pro polymorphisms. The frequency of Tp53 72 Pro/Pro genotype was significantly higher in UL women compared to controls. The risk of UL was 1.5 fold higher in women with the Pro/Pro genotype (OR, 1.5 [95% CI, 1.1 to 2.1], p = 0.012). Moreover, the frequency of the Pro allele was significantly higher in the UL women. Although the frequency of XRCC1 Arg399Gln genotypes did not significantly differ between UL and control groups before adjusting for age, there was an association between the XRCC1 Arg/Gln genotype and UL after adjusting for age (OR, 1.8 [95% CI, 1.1 to 3]). No association was observed between the XRCC1 Arg194Trp polymorphism and UL. The Pro/Pro genotype of Tp53 Arg72Pro polymorphism was associated with UL susceptibility. In addition, the XRCC1 Arg/Gln genotype was associated with increased risk of UL after adjusting for age.     

An updated meta-analysis of the p53 codon 72 polymorphism and gastric cancer risk

To investigate the association between p53 codon 72 polymorphisms and gastric cancer risk, a meta-analysis published in 2007 was updated with new data. Relevant literature was retrieved by searching PubMed and statistical analysis conducted using Review Manager software. Twenty-eight case-control studies were included in this meta-analysis, with 6,859 cases and 9,277 controls. The pooled results for all included studies showed that patients with gastric cancer had a borderline lower frequency of the Arg/Arg phenotype (odds ratio (OR) = 0.91, 95 % CI = 0.83-1.00, p = 0.04). When stratified for race, the difference in Arg/Arg frequency was significant among Asians (OR = 0.87, 95 % CI = 0.78-0.97, p = 0.01). On stratifying the various studies we found that, among Asians: (i) patients with cardial gastric cancer had a significantly higher frequency of the Pro/Pro genotype (OR = 1.35, 95 % CI = 1.03-1.77, p = 0.04) than those with non-cardial gastric cancer; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/Arg (OR = 1.30, 95 % CI = 1.06-1.61, p = 0.01) than those with early (stage I/II) cancer; and (iii) patients with metastasis had a significantly higher frequency of Pro/Pro (OR = 3.31, 95 % CI = 1.31-8.41) than those without metastasis. Our study suggests that, among Asians, the p53 codon 72 Arg/Arg genotype is associated with a modestly decreased risk of gastric cancer, and that this difference in genotype distribution may be associated with cancer stage, location, differentiation and metastasis.