p53 Codon 72 polymorphism and urothelial cancer risk

The p53 tumor suppressor gene is often mutated in various human cancers. Recently, the p53 codon 72 polymorphism has been extensively studied to determine the risk factors responsible for cancer formation. We investigated the genotype distribution of the p53 codon 72 polymorphism in 112 male urothelial cancer cases and 175 male unrelated non-cancer controls. The allelic frequencies in Japanese non-cancer controls were 0.58 (Arg) and 0.42 (Pro). There was no significant difference in the three genotype frequencies (Arg/Arg, Arg/Pro, Pro/Pro) of the p53 codon 72 between the urothelial cancer cases and the controls. However, stratifying by smoking status, we found that the frequency of the Pro/Pro genotype for smokers was significantly more than that for never-smokers (odds ratio (OR)=2.28, 95% confidence interval (95%CI)=1.12-4.66). Furthermore, we divided smoking status (pack-years) into quartiles (<20, 20-40, 40-60, >60). OR (Pro/Pro vs. Arg/Arg) for the lighter smokers (<20 pack-years) was higher than in other groups (OR=6.83). Our results suggest that the Pro/Pro genotype of the p53 codon 72 polymorphism increases the risk of urothelial cancer in smokers.     

P53 Arg72Pro polymorphism and bladder cancer risk--meta-analysis evidence for a link in Asians but not Caucasians

Objective: Individual studies of the associations between P53 codon 72 polymorphism (rs1042522) and bladdercancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship,we performed this systemic review and meta-analysis based on 15 publications. Methods: We used odds ratios(ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Results: We found that therewas no association between P53 codon 72 polymorphism and bladder cancer risk in the comparisons of Pro/Pro vs Arg/Arg; Pro/Arg vs. Arg/Arg; Pro/Pro plus Pro/Arg vs. Arg/Arg; Arg/Arg vs. Pro/Arg plus Arg/Arg(OR=1.06 95%CI 0.81-1.39; OR=1.06 95%CI 0.83-1.36; OR=0.98 95%CI 0.78-1.23; OR=1.06 95%CI 0.84-1.32).However, a significantly increased risk of bladder cancer was found among Asians in the homozygote comparison(Pro/Pro vs. Arg/Arg, OR=1.36 95%CI 1.05-1.75, P=0.790 for heterogeneity) and the dominant model (Arg/Proplus Pro/Pro vs. Arg/Arg, OR=1.26 95%CI 1.05-1.52, P=0.564 for heterogeneity). In contrast, no evidence of anassociation between bladder cancer risk and P53 genotype was observed among Caucasian population in anygenetic model. When stratifying for the stage of bladder, no statistical association were found (Pro/Pro vs. Arg/Arg, OR=0.45 95%CI 0.17-1.21; Pro/Arg vs. Arg/Arg, OR=0.60 95%CI 0.28-1.27; Dominant model, OR=0.5695%CI 0.26-1.20; Recessive model, OR=0.62 95%CI0.35-1.08) between P53 codon 72 polymorphism and bladdercancer in all comparisons. Conclusions: Despite the limitations, the results of the present meta-analysis suggestthat, in the P53 codon 72, Pro/Pro type and dominant mode might increase the susceptibility to bladder cancerin Asians; and there are no association between genotype distribution and the stage of bladder cancer.     

Association Between p53 codon 72 Polymorphism and Cervical Cancer Risk Among Asians: a Huge Review and Meta-analysis

Objective: The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive amore precise estimation of the association between p53 codon 72 polymorphism (Arg72Pro, rs1042522 G>C) andcervical cancer risk among Asians. Methods: A literature search of Pubmed, Embase, Web of Science and CBMdatabases from inception through June 2012 was conducted. The meta-analysis was performed using STATA12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength ofany association. Twenty-eight case-control studies were included with a total of 3,580 cervical cancer cases and3,827 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed thatthe Pro/Pro genotype was associated with increased risk of cervical cancer under the heterozygous model (Pro/Pro vs. Arg/Pro: OR = 1.25, 95%CI: 1.02-1.53, P= 0.005). However, no statistically significant associations werefound under four other genetic models (Pro vs. Arg: OR = 0.97, 95%CI: 0.85-1.10, P= 0.624; Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 0.84, 95%CI: 0.70-1.01, P= 0.058; Pro/Pro vs. Arg/Arg + Arg/Pro: OR = 1.13, 95%CI:0.92-1.39, P= 0.242; Pro/Pro vs. Arg/Arg: OR = 0.97, 95%CI: 0.76-1.22, P= 0.765; respectively). In the subgroupanalysis based on country, the Pro/Pro genotype and Pro carrier showed significant associations with increasedrisk of cervical cancer among Indian populations, but not among Chinese, Japanese and Korean populations.Conclusion: Results from the current meta-analysis suggests that p53 codon 72 polymorphism might be associatedwith increased risk of cervical cancer, especially among Indians.     

P53 Polymorphism at Codon 72 is Associated with Keratocystic Odontogenic Tumors in the Thai Population

Objective: To clarify the association between the p53 polymorphism at codon 72 and susceptibility to thesporadic keratocystic odontogenic tumor (KCOT). Design: One hundred KCOTs and 160 match-group healthycontrols were genotyped to ascertain the frequency of the p53 codon 72 polymorphism using polymerase chainreaction-restriction fragment length polymorphism (PCR-RFLP), confirmed by direct sequencing. Results: Thefrequencies of the Pro/Pro, Arg/Pro, and Arg/Arg genotypes were 23.8%, 49.4%, and 26.9%, respectively, inthe controls, while the KCOT cohort demonstrated 43.0%, 39.0%, and 18.0%, respectively. Further analysissuggested that p53 Pro could be a KCOT-susceptible allele (OR (95%CI)=1.77 (1.22 to 2.59), p=0.0024), with asex-adjusted OR (95%CI) of 1.71 (1.17-2.50), p=0.0046. Moreover, the results indicated that p53 codon 72 Prohomozygous was associated with a two-fold risk of developing KCOT (adjusted OR (95%CI) =2.17(1.23-3.84),p=0.0062). Conclusions: The C/C genotype of P53 gene codon 72 increases the risk of developing sporadic KCOTand may be a useful tool for screening and diagnostic purposes.     

The p53 Codon 72 Polymorphism and Risk of Oral Cancer in Southern Thailand

The codon 72 polymorphism of the p53 tumor suppressor gene has been investigated extensively for its association ‍with various cancers around the world. However, its influence has not been elucidated in the Thai population. ‍Therefore, a case-control study with 97 patients and 97 matched controls was conducted to elucidate the association ‍between the polymorphic p53 and oral cancer risk in a Southern Thai population. The frequencies of the Arg/Arg, ‍Arg/Pro, and Pro/Pro genotypes were 36%, 35%, and 29%, respectively in the controls and 33%, 45% and 22%, ‍respectively in the patients. This study shows that there was no significant association between the p53 codon 72 ‍polymorphism and oral cancer risk. There was also no link with respect to smoking or drinking habits. However, ‍our data suggest that for individuals who were younger than 65 years old, the Pro/Pro genotype may offer some ‍protection against oral cancer (OR = 0.13, 95%CI 0.04-1.10). This is the first report on p53 polymorphism and oral ‍cancer in Thailand.‍ ‍     

P53 codon 72 polymorphism and risk of gastric cancer in a Chinese population

The p53 gene plays an important role in cell cycle control in response to DNA damage, which may increase the probability of mutations that lead to carcinogenesis. The p53 codon 72 Arg right curved arrow Pro polymorphism has been suggested to be associated with risk for different kind of cancers, but the data on gastric cancer (GC) is very limited. To evaluate the association between this polymorphism and risk of GC, we performed genotype analysis by using a polymerase chain reaction-based restriction fragment length polymorphism assay in a population-based case-control study of 324 GC patients and 317 cancer-free controls in a Chinese population. The controls were frequency-matched to the cases by age, sex and smoking status. The frequency of the p53 Arg allele was 57.4% in the cases and 54.9% in the controls, and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 29.6%, 55.6%, and 14.8%, respectively, in the cases, and 29.6%, 50.5%, and 19.9%, respectively, in the controls (p=0.207). Logistic regression analysis revealed that the p53 Arg allele (Arg/Pro and Arg/Arg genotype) was associated with a borderline significantly increased risk of gastric cancer (adjusted OR=1.44, 95% CI=0.95-2.18), particularly non-cardia gastric cancer (adjusted OR=1.67, 95% CI=1.00-2.77), compared with p53 homozygous Pro allele (Pro/Pro genotype), and the risk was significantly more evident among alcohol drinkers (adjusted OR=2.85, 95% CI=1.37-5.95). While the results suggest that the p53 codon 72 polymorphism may contribute to gastric cancer susceptibility, further larger studies are needed to substantiate our findings and to explore a possible interaction between p53 codon 72 polymorphism and alcohol in the etiology of gastric cancer.     

p53codon72单核苷酸多态性与肝细胞癌发病风险的关系

[目的]探讨广西地区p53基因codon72单核苷酸多态性(SNP)与肝细胞癌(HCC)发病风险的关系。[方法]采用TaqMan MGB探针等位基因分型技术对985例肝癌病例和相匹配的992例非肿瘤对照的p53 codon72(Arg>Pro,rs1042522)基因型进行检测,并分析该SNP与肝癌发病风险的关系。[结果]p53 codon72多态性与肝癌发病风险之间无统计学关联(Arg/Pro:校正OR=1.15,95%CI:0.83～1.59;Pro/Pro:校正OR=1.16,95%CI:0.80～1.68;Arg/Pro+Pro/Pro:校正OR=1.15,95%CI:0.85～1.57)。按是否吸烟、饮酒、HBV和HCV感染分层分析,亦未发现p53 codon72多态性与肝癌发病风险有关。但基因—环境交互作用显示,该基因多态性与吸烟、饮酒和HBV感染存在交互作用,OR值分别为2.42(95%CI:1.47～3.97)、2.96(95%CI:1.82～4.80)和62.74(95%CI:34.39～114.46)。[结论]p53codon72的单独效应可能与肝癌易感性无关联,但该SNP与吸烟、饮酒和HBV感染存在基因—环境交互作用,增加肝癌的发病风险。     

鼠双微体同源基因2遗传多态与结直肠癌患病风险的相关性

目的 探讨p53 72 Arg→Pro和鼠双微体同源基因2(MDM2) 309 T→G多态与结直肠癌(CRC)发生发展的关系.方法 采用病例-对照关联研究方法,分析1000例CRC和1300例正常对照中p53 72 Arg→Pro和MDM2 309 T→G的基因型.以多因素Logistic回归模型计算各基因型的比值比(OR)及其95%可信区间(CI).结果 携带MDM2 309 GG或TG基因型者患CRC的风险比TT基因型者显著增高,OR分别为2.06(95%CI为1.62～2.62)和1.31(95%CI为1.06～1.62).p53 72 Arg→Pro多态与CRC风险不相关.两个基因多态联合分析表明,既携带MDM2 309 GG,又携带p53 72 Pro/Pro基因型者,患CRC的OR显著高于携带MDM2 309 TT和p53 72 Pro/Pro基因型者[2.75(95%CI为1.60～4.70)比1.09(95%CI为0.63～1.88);χ2=9.83,P=0.002].结论 MDM2基因的遗传多态可能是CRC的遗传易感性因素.     

No Evidence of Association of the Arg72Pro p53 Gene Polymorphism with Cancer Risk in the Saudi Population: a Meta-Analysis

Background: Earlier studies on the association between p53 codon 72 Arg>Pro polymorphism and cancerrisk were inconclusive and conflicting for the Saudi population. Therefore, we performed a meta-analysis toinvestigate the relationship between the codon 72 Arg>Pro polymorphism and overall cancer risk in SaudiArabia. Materials and Methods: We searched all eligible published studies and data were pooled together toperform the meta-analysis. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculatedfor homozygous, heterozygous, dominant and recessive genetic models. Results: A total of five eligible publishedstudies covering 502 cancer cases and 784 healthy controls were included in the meta-analysis. No publicationbias was detected in this study. The results suggested that the variant (Pro vs Arg: p=0.960; OR=1.004, 95%CI=0.852-1.183), homozygous (Pro.Pro vs Arg.Arg: p=0.970; OR=1.006, 95% CI=0.729-1.390), heterozygous(Arg.Pro vs Arg.Arg: p=0.473; OR=0.783, 95% CI=0.402-1.527) carriers were not associated with overall cancerrisk. Similarly, dominant (Pro.Pro+Pro.Arg vs Arg.Arg: p=0.632; OR=0.886, 95% CI=0.540-1.454) and recessive(Pro.Pro vs Pro.Arg+Arg.Arg: p=0.269; OR=1.163, 95%CI=0.890-1.521) models also did not indicate increasedrisk of cancer. Conclusions: The current meta-analysis suggests that the codon 72 Arg>Pro polymorphism ofthe p53 gene might not contribute to cancer susceptibility in Saudi population. Future well designed large casecontrol studies are needed to validate our findings.     

Updated meta-analysis of the TP53 Arg72Pro polymorphism and gastric cancer risk

Objective: The p53 tumor suppressor pathway plays an important role in gastric cancer (GC) development.Auto-regulatory feedback control of p53 expression is critical to maintaining proper tumor suppressor function. Sofar, several studies between p53 Arg72Pro polymorphism and GC have generated controversial and inconclusiveresults. Methods: To better assess the purported relationship, we performed a meta-analysis of 19 publications.Eligible studies were identified by searching the Pubmed database. Odds ratios (ORs) with 95% confidenceintervals (CIs) were estimated to assess any link. Results: Overall, a significant association was detected betweenthe p53 Arg72Pro polymorphism and GC risk (Pro-allele vs. Arg-allele: OR = 1.05, 95%CI = 1.01-1.08; Pro/Provs. Arg/Arg: OR = 1.13, 95%CI = 1.04-1.22). Moreover, on stratified analysis by race, significantly increased riskwas found for Asian populations (Pro-allele vs. Arg-allele: OR = 1.06, 95%CI = 1.02-1.10; Pro/Pro vs. Arg/Arg:OR = 1.16, 95%CI = 1.07-1.26; Pro/Pro+Pro/Arg vs. Arg/Arg: OR = 1.58, 95%CI = 1.09-2.27). Conclusions: Ourstudy provided evidence that the p53 72Pro allele may increase GC risk in Asians. Future studies with largersample size are warranted to further confirm this association in more detail.     

P53 codon 72 Arg/Pro polymorphism and lung cancer risk in Asians: an updated meta-analysis

The polymorphism of p53 codon 72, a transversion of G to C (Arg to Pro), has been demonstrated to be associated with the risk for lung cancer. However, individual studies conducted in Asians have provided conflicting and inconclusive findings. Thus, we performed a meta-analysis by pooling all currently available case–control studies to estimate the effect of p53 codon 72 Arg/Pro polymorphism on the development of lung cancer. The pooled odds ratios (ORs) with the corresponding 95 % confidence intervals (95 %CIs) were calculated to assess this effect. A total of 14 individual studies involving 7,929 cases and 5,924 controls were included into this meta-analysis according to the inclusion criteria. The overall OR for the dominant genetic model indicated that the p53 codon 72 Arg/Pro variant was positively correlated with lung cancer risk (OR_{Arg/Pro + Pro/Pro vs. Arg/Arg}?=?1.14, 95 %CI 1.07–1.23, P _OR?<?0.001). Similar results were found in the stratified analysis of population-based studies. The histological types of lung cancer and smoking status seemed to exert no effect on the lung cancer risk. Sensitivity analysis confirmed the stability of the above findings. The updated meta-analysis suggests that the p53 codon 72 Arg/Pro polymorphism is a risk factor for lung cancer in the Asian population. However, the potential role of gene–environment interaction in lung cancer susceptibility needs further investigation in future studies with high quality.     

R72P Polymorphism of TP53 in Ulcerative Colitis Patients is Associated with the Incidence of Colectomy, Use of Steroids and the Presence of a Positive Family History

P53 tumor suppressor protein is one of the pivotal regulators for genome integrity, cell cycle and apoptosis. The most commonly and extensively studied single nucleotide polymorphism (SNP) of p53 is Arg>Pro substitution on codon 72 (R72P). Although we know that the SNP has unique functional effects on the protein, its clinical significance is not clearly identified yet. Aim of the study was to access the relationship between R72P genotype distribution and clinical variables in patients with ulcerative colitis (UC) and colorectal cancer (CRC). Genomic DNA samples were extracted from 95 UC, 50 CRC, and 219 healthy controls. R72P genotype analysis was carried out with polymerase chain reaction following by restriction enzyme digestion. We observed that Pro allele carriage is a strong risk factor for CRC (OR?=?3.03; 95%CI?=?1.91–2.40; p?=?0.003), but only modest association with UC (OR?=?1.61; 95%CI?=?0.98–2.65; p?=?0.059) (Pro/Pro and Pro/Arg genotypes vs. Arg/Arg genotype). We did not find any correlation between genotype distribution of the polymorphism and clinical parameters of CRC, but in UC, Pro/Pro genotype was significantly related to an inflammatory bowel disease family history (OR?=?8.0; 95%CI?=?1.68–38.08, p?=?0.015), and Arg/Pro genotype was significantly associated with the history of disease-related colectomy (OR?=?17.77; 95%CI?=?0.98–323.34, p?=?0.012) and steroid use (OR?=?10.14; 95%CI?=?2.63–39.12, p?=?0.0002). Our data suggest that R72P variant seems to be associated with high risk for development of CRC but carries low risk for development of UC. R72P genotypes might be a useful predictive marker for surgical and medical treatment of UC.     

p53 Arg72Pro polymorphism and risk of colorectal adenoma and cancer

A single nucleotide polymorphism (SNP) at codon 72 of the p53 gene (Arg72Pro) alters the p53 protein structure and affects its activity. We investigated this SNP in relation to colorectal adenoma and cancer among men and women from case-control studies nested within the Nurses' Health Study, the Health Professionals Follow-up Study and the Physicians' Health Study. Among 856 colorectal adenoma cases and 1,184 controls, we observed a modest association with p53 Arg72Pro genotype (multivariate odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.04-1.50 for Arg/Pro and Pro/Pro vs. Arg/Arg). This association did not vary by colorectal site or by sex. Among 442 colorectal cancer cases and 904 controls, we observed no significant overall association between p53 Arg72Pro genotype and colorectal cancer (multivariate OR = 1.14, 95% CI = 0.90-1.45). However, when colorectal site and sex was accounted for, the Pro carrier genotypes compared to Arg/Arg were associated with an increased risk of proximal colon cancers in women (multivariate OR = 2.59, 95% CI = 1.49-4.52) though not with distal colon or rectal cancers, while among men the same genotypes were associated with an increased risk of distal colon cancers (multivariate OR = 2.09, 95% CI = 1.28-3.40) but not proximal colon or rectal cancers. Our results suggest that Arg72Pro may play a role in the early stages of colorectal neoplasia and possibly in progression to invasive disease, depending on site and sex.     

p53基因第72位密码子多态性与肺癌临床病理特征及预后关系的Meta分析

目的 系统评价p53基因第72位密码子的多态性与肺癌临床病理特征及预后的关系。方法计算机检索PubMed、中国知网、维普、万方等数据库,收集有关p53基因第72位密码子多态性与肺癌临床病理特征及预后关系的研究。检索时限均从各文献数据库建库时间至2013年12月20日。由2名研究者按照纳入与排除标准独立筛选文献、提取资料和质量评价后,采用RevMan50软件进行Meta分析,计算比值比（OR）及其95%可信区间（CI）并行敏感性分析和发表偏倚评估。结果 纳入11项研究,共2730例患者。Meta分析结果显示,男性患者中p53基因第72位密码子Arg／Arg 或Arg／Pro表型多见,与女性患者相比,差异有统计学意义（OR=1.58,95％CI：1.04～2.40,P=0.03）。p53基因第72位密码子Pro／Pro表型在非鳞癌患者中居多,与鳞癌患者相比,差异有统计学意义（OR=0.69,95％CI：0.49～0.97,P=0.03）。而p53基因第72位密码子多态性与肺癌患者的吸烟史、临床分期、3年生存率无明显相关（P＞0.05）。结论 p53基因第72位密码子的多态性与肺癌患者的预后无明显相关。由于纳入研究的质量和数量有限,降低了本系统评价的证据强度,本系统评价的结论仅供临床研究与实践参考。     

Role of GSTM1 (Null/Present), GSTP1 (Ile105Val) and P53 (Arg72Pro) Genetic Polymorphisms and the Risk of Breast Cancer - A Case Control Study from South India

The present study was undertaken to examine the frequencies of GSTM1 (Null/Present), GSTP1 (Ile105Val)and p53 (Arg72Pro) genotypes and their relations to breast cancer susceptibility in South Indian women. Thiscase - control study involved 250 consecutive breast cancer cases and 500 healthy controls matched in five-yearage categories in the ratio of 1:2. Genotyping was performed by PCR for GSTM1, Real-Time Allelic discriminationassay for GSTP1 and PCR-CTPP for p53. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculatedusing conditional logistic regression after adjusting for the known risk factors for breast cancer. The frequenciesfor the GSTM1 Null genotype were 26% in the cases and 22% in the controls; for GSTP1 Ile/Ile, Ile/Val, Val/Valthe frequencies were 46.6%, 41.9% and 11.5%, respectively, in cases and 46.0%, 43.8% and 10.2% in controls;for p53 Arg/Arg, Arg/Pro & Pro/Pro the frequencies were 26.4%, 50.0% and 23.6% in cases and 27.0%, 44.8%and 28.2% in controls. A nonsignificant elevation in breast cancer risk was observed among women who had theGSTM1 Null genotype (OR=1.24; 95% CI=0.83-1.84), the p53 Arg/Arg genotype (OR=1.28; 95% CI=0.81-2.03)and the Pro/Arg genotype (OR=1.49; 95% CI=0.99-2.25), and the GSTP1 Val/Val genotype (OR=1.1; 95%CI=0.64-1.91).     

Genetic polymorphisms of p53 and GSTP1,but not NAT2,are associated with susceptibility to squamous-cell carcinoma of the esophagus

The interaction of genetic and environmental factors can determine an individual's susceptibility to various cancers. We present a hospital-based case-control study, which included 90 patients of esophageal squamous-cell carcinoma (ESCC) and 254 healthy people in Taiwan, to investigate the effects of genetic polymorphisms of p53, GSTP1 and NAT2 on the risk of ESCC. Polymorphisms of p53, NAT2 and GSTP1 were determined by PCR-RFLP. The codon 72 p53 Pro allele was more frequently found in ESCC patients [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.04-3.35 for Arg/Pro genotype and OR 2.56, 95% CI 1.29-5.08 for Pro/Pro genotype]. In cigarette smokers, the frequency of GSTP1 Ile/Ile genotype was higher in ESCC patients (OR 2.8, 95% CI 1.4-5.7). Among alcohol drinkers, borderline significance was also found for GSTP1 Ile/Ile genotype (OR 2.0, 95% CI 0.9-4.4). Results were not similar for the NAT2 genetic polymorphism. Using logistic analyses, we found that individuals with p53 Pro/Pro genotype had a significantly higher risk of developing ESCC than those with Arg/Arg genotype (OR 2.3, 95% CI 1. 1-5.1), after adjusting for other significant environmental risk factors. This result remained similar (OR 2.2, 95% CI 1.0-4.8 for p53 Pro/Pro vs. Arg/Arg), even after further adjustment for NAT2 and GSTP1 polymorphisms. The codon 72 p53 Pro/Pro genotype in the general population and GSTP1 Ile/Ile in cigarette smokers may predict a higher risk of developing ESCC.     

Association of a p53 Codon 72 Gene Polymorphism with Environmental Factors and Risk of Lung Cancer: a Case Control Study in Mizoram and Manipur,a High Incidence Region in North East India

Background: A very high incidence of lung cancer is observed in Mizoram and Manipur, North East India.We conducted a population based case control study to establish associations of p53 codon 72 polymorphisms andinteractions with environmental factors for this high incidence. Material and Methods: A total of 272 lung cancercases and 544 controls matched for age (±5 years), sex and ethnicity were collected and p53 codon 72 polymorphismgenotypes were analyzed using a polymerase chain based restriction fragment length polymorphism assay. Weused conditional multiple logistic regression analysis to calculate adjusted odds ratios and 95% confidenceintervals after adjusting for confounding factors. Results: p53 Pro/Pro genotype was significantly associated withincreased risk of lung cancer in the study population (adjusted OR=2.14, CI=1.35-3.38, p=0.001). Interactionsof the p53 Pro/Pro genotype with exposure to wood smoke (adjusted OR=3.60, CI=1.85-6.98, p<0.001) andcooking oil fumes (adjusted OR=3.27, CI=1.55-6.87, p=0.002), betel quid chewing (adjusted OR=3.85, CI=1.96-7.55, p<0.001), tobacco smoking (adjusted OR=4.42, CI=2.27-8.63, p<0.001) and alcohol consumption (adjustedOR=3.31, CI=1.10-10.03, p=0.034) were significant regarding the increased risk of lung cancer in the studypopulation. Conclusions: The present study provided preliminary evidence that a p53 codon 72 polymorphismmay effect lung cancer risk in the study population, interacting synergistically with environmental factors.     

The p53 codon 72 polymorphism, sunburns, and risk of skin cancer in US Caucasian women

The p53 gene is involved in the control of cell-cycle arrest and apoptosis. The germline Arg72Pro polymorphism alters the protein's biochemical functions, and may confer individual susceptibility to skin cancer. We evaluated the association of the Arg72Pro polymorphism with skin cancer risk among Caucasians in a nested case-control study within the Nurses' Health Study (NHS) (219 melanoma, 286 squamous cell carcinoma (SCC), and 300 basal cell carcinoma (BCC) and 874 controls). Compared to the Arg/Arg genotype, the Pro/Pro genotype had an OR of 1.57 (95%CI, 0.81-3.06) for melanoma risk, and an OR of 1.79 (95%CI, 1.01-3.17) for BCC risk. The positive association of the Pro allele with BCC risk was only limited to women with two or fewer lifetime sunburns (P, trend, 0.002; P, interaction, 0.02). No association was observed between the polymorphism and SCC risk. We also observed that the Pro allele was inversely associated with the risk of childhood sunburn among Caucasian participants pooled from four nested case-control studies within the NHS. This study suggests that the Arg72Pro polymorphism may play a role in skin carcinogenesis.     

Linkage of TP53 codon 72 pro/pro genotype as predictive factor for nasopharyngeal carcinoma development.

Genetic predisposition has been suggested as a cofactor for cancer aetiology and a polymorphism in TP53 codon 72 has been associated as a susceptibility factor for several cancers. Nasopharyngeal carcinoma is a rare neoplasia in western civilizations and genetic predisposition might play an important role in its development. We evaluated the linkage of the polymorphic variants (Arg/Pro) on TP53 codon 72 with nasopharyngeal cancer development in a case-control study with 392 individuals from a northern Portuguese population, including 107 patients with nasopharyngeal carcinoma and 285 healthy controls. This study revealed a three-fold risk for carriers of Pro/Pro genotype either against carriers of Arg/Arg (OR=2.62; 95% CI=1.10-6.30; P=0.016) or total Arg carriers (OR=2.67; 95% CI=1.21-5.90; P=0.012). Moreover, step-wise logistic regression analysis identified Pro/Pro genotype (OR=3.1; 95% CI=1.3-7.3; P=0.009), age >49 at diagnosis (OR=2.5; 95% CI=1.6-4.0; P<0.001) and male gender (OR=2.7; 95% CI=1.6-4.4; P<0.001) as predictive factors for the development of nasopharyngeal carcinoma. These results confirm the data from Asiatic populations suggesting that Pro/Pro genotype represents a stable risk factor for nasopharyngeal carcinoma development in Portugal and that TP53 codon 72 polymorphism can contribute as a genetic susceptibility marker, providing additional information to improve the knowledge about nasopharyngeal carcinoma aetiology.     

p53基因codon 72多态性与乳腺癌术后放化疗疗效相关性分析

目的:分析p53基因codon 72多态性与乳腺癌患者术后放化疗的预后相关性。方法:选取北京大学肿瘤医院乳腺癌患者术后接受放化疗427 例,采用聚合酶链反应- 限制性片段长度多态性（PCR-RFLP ）方法分析其p53基因codon 72多态性,比较不同基因型患者间复发及生存的差异。结果:全部患者基因型分布为Pro/Pro 型18.3%（78/427）、Pro/Arg型44.0%（188/427）、Arg/Arg型37.7%（161/427）。3 种基因型间无局部复发生存（LRFS）、无局部区域复发生存（LRRFS ）、无远处转移生存（DDFS）及总生存（OS）均无显著性差异（均P>0.05）。 427 例患者中雌激素受体（ER）阳性为303 例,其中Arg/Arg基因型患者OS明显优于Pro/Pro 基因型患者（χ2=6.330,P=0.042）。 在多因素分析中p53基因codon 72多态性是ER阳性患者LRFS、LRRFS 、DDFS及OS的独立预后因素,Pro/Pro 基因型的患者较Arg/Arg基因型的局部复发风险增加5.9 倍（HR= 5.9,95%CI 1.1～31.1,P=0.036）,局部区域复发风险增加3.1 倍（HR= 3.1,95%CI 1.1～9.1,P=0.039）,远处转移风险增加2.8 倍（HR= 2.8,95%CI 1.3～6.0,P=0.010）,死亡风险增加4 倍（HR= 4.0,95%CI 1.3～12.0,P=0.013）。 结论:在ER阳性的乳腺癌术后接受放化疗患者中,Pro/Pro 基因型的局部及局部区域复发风险、远处转移风险、死亡风险均高于Arg/Arg基因型。