P53 codon 72 polymorphism in breast cancer

Increased and deregulated proliferative activity due to abnormalities in the cell cycle modulators are frequently observed in cancer. A sequence polymorphism at codon 72 of the p53 gene results in either a proline or an arginine and may induce different functional activities. This polymorphism has been shown to have varying ethnic and geographical distribution. It has been reported that the p53 Arg homozygous genotype could be a potential genetic risk factor for cancer. However, not all investigations have been consistent and this hypothesized association remains controversial. The purpose of this study was to investigate the genotype frequencies and association of the p53 codon 72 polymorphism with breast cancer in Turkish patients. A group of 115 patients with breast cancer and a control group of 76 healthy individuals were enrolled in the study. A significantly higher prevalence of homozygosity for the p53 Arg allele was observed in the patients as compared to the controls. Statistical analysis suggested a strong association between the Arg/Arg genotype and breast cancer.     

TP53 codon 72 polymorphism and breast cancer risk in Bangladeshi population

Background

Breast cancer, a hereditary or heterogeneous sporadic disease, is the most common cancer in women worldwide. The tumor suppressor TP53 gene has been found to be the most commonly mutated genes in many types of human cancers, including breast cancer. This study aimed to investigate the association of codon 72 polymorphism of TP53 gene with breast cancer risk in Bangladeshi females.

Methods

The study included 125 cases and 125 healthy controls. Genotyping and polymorphism were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis.

Results

The frequencies of the three genotypes Arg/Arg, Arg/Pro, and Pro/Pro were 43.2, 33.6, and 23.2% in cases, whereas 48.8, 40.8, and 10.4% in controls, respectively. The frequency of mutant homozygous (Pro/Pro) genotype was significantly increased in breast cancer patients as compared with controls (23.2 vs 10.4%), and showed 2.52-fold significantly increased risk for breast cancer (OR 2.5199, 95% CI 1.19–5.33, p = 0.0157). The frequencies of Pro/Pro genotype were significantly higher in breast cancer cases with non-breast feeding status. Pro allele frequency was found to be significantly increased in breast cancer cases (OR 1.4978, 95% CI 1.0357–2.1662, p = 0.0318).

Conclusions

Our data suggest that mutant (Pro/Pro) homozygosity at codon 72 of TP53 gene is significantly associated with breast cancer susceptibility in Bangladeshi women. In addition, this association was significantly related to lactating status.

     

P53 codon 72 polymorphism and gastric cancer: a meta-analysis of the literature

Studies investigating the association between p53 codon 72 polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarize the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 12 case-control studies, which included 1,665 gastric cancer cases and 2,358 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [Arg/Arg odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.79, 1.16; Pro/Pro (OR = 1.21, 95% CI = 0.92, 1.58); Pro/Arg (OR = 0.95, 95% CI = 0.79, 1.14)] between gastric cancer and noncancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly lower frequency of Arg/Arg (OR = 0.84, 95% CI = 0.72, 0.99) than noncancer patients among Asians. Stratified the various studies by the location, stage, Lauren's classification, and histological differentiation of gastric cancer, we found that (i) patients with cardia gastric cancer had a significantly higher frequency of Pro/Pro (OR = 3.20, 95% CI = 1.46,7.01) than those with noncardia gastric cancer among Asians; (ii) patients with advanced (stage III/IV) gastric cancer had a significantly higher frequency of Arg/Arg (OR = 1.48, 95% CI = 1.01, 2.16) than those with early (stage I/II) gastric cancer among Asians; (iii) patients with poor differentiation had a significantly lower frequency of Pro/Pro (OR = 0.13, 95% CI = 0.03, 0.64) than those with well differentiation among Caucasians. This meta-analysis suggests that the p53 codon 72 polymorphism may be associated with gastric cancer among Asians, and that difference in genotype distribution may be associated with the location, stage, and histological differentiation of gastric cancer.     

Association between the P53 codon 72 polymorphism and nasopharyngeal cancer risk

The P53 codon 72 polymorphism has been identified as a critical biomarker in modifying the risk of nasopharyngeal cancer (NPC). Many studies have investigated the association between the polymorphism of P53 codon 72 and NPC risk; however, the findings across the published studies are inconsistent and inconclusive. To acquire a more precise assessment for this association, we conducted an updated meta-analysis. The PubMed, Embase, Web of Science, and Wanfang databases were searched for relevant case–control studies. Totally, seven independent publications with 1,133 cases and 1,678 controls were retrieved. The pooled odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was calculated. Increased risk of NPC was observed among individuals carrying the variant allele and genotypes of P53 codon 72 (OR _{Pro vs. Arg}?=?1.32, 95 % CI 1.18–1.47, P _OR?<?0.001; OR _{ProPro vs. ArgArg}?=?1.90, 95 % CI 1.51–2.39, P _OR?<?0.001; OR _{ProArg + ProPro vs. ArgArg}?=?1.33, 95 % CI 1.13–1.57, P _OR?=?0.001; OR _{ProPro vs. ArgArg + ProArg}?=?1.65, 95 % CI 1.35–2.01, P _OR?<?0.001). Stratified analyses by ethnicity and source of controls also identified this significant relationship in Asians, Caucasians, and hospital-based case–control studies. There was no publication bias risk in our study. The updated meta-analysis supports the evidence that the polymorphism of P53 codon 72 is a risk factor for the development of NPC among the populations of both Asian and Caucasian.     

p53 codon 72 polymorphism and the risk of lung cancer in a Korean population

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of lung cancer (LC) in a South Korean population. We conducted a population-based, large-scale, case-control study including 3939 patients with LC and 1700 controls. P53 codon 72 polymorphism was determined by real-time polymerase chain reaction (PCR). The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in LC were 37.0%, 46.2%, and 16.7%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively (p < 0.01). The Arg/Pro and Pro/Pro genotype were significantly associated with increased risk of LC (odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.06-1.14 and OR = 1.83, 95% CI = 1.48-2.26, respectively) compared with the Arg/Arg genotype. Risk was compared in different subgroups. The OR of Pro/Pro genotype was significantly higher in small cell lung cancer (SCC) and squamous cell carcinoma (SQC) than in adenocarcinoma (ADC). Higher OR of Pro/Pro genotype was also seen among males. However, relationships between gender, age, smoking, and genotypes were not found. P53 codon 72 polymorphism was associated with an increased risk of LC in this Korean population; the association was especially noteworthy in SQC, SCC, and males.     

p53 codon 72 polymorphism in patients with gastric and colorectal cancer in a Korean population

Background

The common p53 codon 72 polymorphism has been investigated as a risk factor for cancer in different populations; however, the results have been inconsistent. This study investigated the risk of developing gastric or colorectal cancer associated with the p53 codon 72 polymorphism in a Korean population.

Methods

We conducted a large-scale case?Ccontrol study that included 2,213 gastric cancer patients; 1,829 colorectal cancer patients; and 1,700 healthy controls. Genotyping was performed with real-time polymerase chain reaction (PCR), using a TaqMan single-nucleotide polymorphism (SNP) genotyping assay.

Results

The frequencies of Arg/Arg, Arg/Pro, and Pro/Pro genotypes of the p53 codon 72 polymorphism were 43.3, 42.0, and 13.0% in the gastric cancer patients; 40.5, 45.0, and 14.0% in the colorectal cancer patients; and 43.2, 45.6, and 11.2% in the controls, respectively. The Pro/Pro genotype was associated with an increased risk of gastric [age- and sex-adjusted odds ratio (OR)?=?1.25, 95% confidence interval (CI)?=?1.01?C1.56, P?=?0.04] and colorectal cancer (OR?=?1.36, 95% CI?=?1.07?C1.72, P?=?0.01). There were no significant interactions between the p53 codon 72 polymorphism and smoking or drinking.

Conclusions

Our results suggest that the Pro/Pro genotype is associated with modest increases in the risks of gastric cancer and colorectal cancer in a Korean population.     

Lung cancer risk in relation to TP53 codon 47 and codon 72 polymorphism in Bangladeshi population

The objective of this study was to determine whether p53 codon 47 and codon 72 polymorphisms are associated with increased risk of lung cancer in Bangladeshi population. We carried out a case-control study and examined the genotype distribution Pro47Ser and Arg72Pro single-nucleotide polymorphisms along with tobacco smoking in the predisposition of lung cancer by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The study included 106 lung cancer patients and 116 control subjects from Bangladesh. Lung cancer risk was estimated as odds ratio (OR) and 95 % confidence interval (CI) using conditional logistic regression models adjusting for age, sex, and smoking. No significant association was found between Pro47Ser SNP and lung cancer. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in lung cancer were 25.5, 37.7, and 36.8 %, respectively; frequencies in the controls were 53.4, 30.2, and 16.4 %, respectively (p?Arg/Pro and Pro/Pro genotype were significantly associated with increased risk of lung cancer (OR?=?2.51, 95 % CI?=?1.38–4.82 and OR?=?4.62, 95 % CI?=?2.31–9.52, respectively) compared with the Arg/Arg genotype. The combined frequency of Arg/pro and Pro/Pro genotype was also found to be associated with elevated risk of lung cancer (OR?=?3.36, 95 % CI?=?1.90–5.94, p?χ ² ?=?33.94, p?=?0.00000004) in case of heavy smokers (40 packs per year or more). We conclude that not Pro47Ser SNP but Arg72Pro SNP is involved in susceptibility to developing lung cancer, at least in Bangladeshi population.     

Association of the TP53 codon 72 polymorphism with colorectal cancer in a Chinese population

A TP53 gene polymorphism, resulting in an arginine (R) to proline (P) at codon 72 (TP53 R72P), has been associated with the susceptibility to various cancers. To better understand the role of this polymorphism in colorectal cancer etiology, we examined the association between TP53 R72P and colorectal cancer risk in 345 patients with colorectal cancer and 670 controls in a Chinese population. We observed that subjects with RP and PP genotypes had a 1.60-fold and a 2.37-fold increased risk for colorectal cancer, respectively. The 72P allele conferred a more pronounced increase in colorectal cancer risk among alcohol consumers (heterozygotes: OR = 3.01; homozygotes: OR = 4.71). The TP53 R72P polymorphism was not linked to tumor location, histologic grade, lymph node metastases, Dukes stage, p53 positivity, or age at diagnosis, but to tumor size. We conclude that the TP53 R72P polymorphism may contribute to the etiology of colorectal cancer in the Chinese population, particularly among alcohol consumers.     

P53 codon 72 polymorphism and lung cancer risk: evidence from 27,958 subjects

The role of p53 codon 72 polymorphism in the development of lung cancer remains obscure due to inconsistent findings of individual case–control studies published to date. A meta-analysis was conducted to better estimate the association between the p53 codon 72 variant and lung cancer risk. All relevant publications from the PubMed, Embase, Web of Science, and Wanfang databases were retrieved. Based on the inclusion criteria, 39 publications involving 44 independent case–control studies were finally included into this meta-analysis. Data were extracted and the pooled odds ratio (OR) with the corresponding 95 % confidence interval (95 % CI) was calculated. The overall pooled ORs showed no significant relationship of the p53 codon 72 polymorphism with increased or decreased risk of lung cancer in all gene contrast models (OR _{Pro vs. Arg}?=?1.04, 95 % CI?=?0.96–1.13, P _OR?<?0.001; OR _{Pro/Pro vs. Arg/Arg}?=?1.07, 95 % CI?=?0.91–1.25, P _OR?<?0.001; OR _{Arg/Pro vs. Arg/Arg} =1.04, 95 % CI?=?0.94–1.15, P _OR?<?0.001; OR _{Pro/Pro + Arg/Pro vs. Arg/Arg}?=?1.04, 95 % CI?=?0.94–1.16, P _OR?<?0.001; OR _{Pro/Pro vs. Arg/Arg + Arg/Pro}?=?1.07, 95 % CI?=?0.93–1.23, P _OR?<?0.001). According to the ethnicity, no significant association was observed in subgroup analyses of the Asians, Caucasians, Africans and the mixed population. Similar finding was found in subgroup analyses of hospital-based and population-based studies. Concerning the histological types of lung cancer, the p53 codon 72 variant exerts risk effect on the lung carcinogenesis in patients with adenocarcinoma (OR _{Arg/Pro vs. Arg/Arg}?=?1.10, 95 % CI?=?1.00–1.22, P _OR?=?0.048). Additionally, subgroup analysis by the smoking status demonstrated that the p53 codon 72 variant seemed to play a protective role in lung carcinogenesis among the non-smokers but not the smokers in the contrast model of Arg/Pro vs. Arg/Arg (OR _{Arg/Pro vs. Arg/Arg}?=?0.71, 95 % CI?=?0.50–1.00, P _OR?=?0.049). The present meta-analysis suggests the p53 codon 72 polymorphism may weakly modify the risk for lung cancer among the adenocarcinoma patients and non-smokers. Nevertheless, this association needs further confirmation in future studies with high quality.     

The p53 codon 72 polymorphism and lung cancer risk.

The p53 tumor suppressor gene frequently is mutated in many forms of human carcinomas. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). This p53 polymorphism reportedly is associated with lung cancer susceptibility. However, not all investigations have been consistent, and this hypothesized association remains controversial. We tested the hypothesis that the Pro/Pro genotype is associated with increased lung cancer risk in a large case-control study of lung cancer that included 482 cases and 510 controls from the Massachusetts General Hospital in Boston, Massachusetts. DNA from peripheral blood samples was examined by PCR-RFLP. Pro/Pro homozygotes were found more frequently in adenocarcinomas (cases, 16.4%; controls, 12.0%; P = 0.03). The prevalence of the Pro/Pro homozygous genotype increased in frequency with increasing pack-years of smoking. The combined susceptible genotype homozygous Pro/Pro and heterozygous Arg/Pro was associated with a 1.45-fold higher risk of adenocarcinoma compared with Arg/Arg genotype (95% confidence interval = 1.01-2.06; P = 0.04) after adjustment for relevant variables. Lung adenocarcinoma risk increased with the presence of one or both variant alleles across smoking strata. In addition, at each level of smoking (except nonsmoker and light smoker), the risk associated with smoking was higher for the population with the combined variant (Arg/Pro + Pro/Pro) genotype. The risk for the combined genotype was associated with tobacco exposure status. In conclusion, the codon 72 germ-line polymorphism (Arg/Pro) of the common tumor suppressor gene p53 contributes to heritable susceptibility for smoke-induced lung adenocarcinoma. The modifications by p53 polymorphism and pack-years resulted in an increased risk of the susceptible genotype to lung adenocarcinoma. The p53 gene may modulate the response to environment carcinogens and thereby affect the risk of developing lung adenocarcinoma.     

P53 polymorphism in codon 72 and risk of human papillomavirus-induced cervical cancer: effect of inter-laboratory variation

An association between codon-72 p53 polymorphism and risk of human papillomavirus (HPV)-induced cervical cancer has been found recently, but it has been difficult to replicate. In this study, we assess the impact of inter-laboratory variation in p53 genotyping on the validity of the proposed association. DNA specimens were randomly selected from 54 invasive, squamous cell carcinoma cases, 52 HPV-negative, and 39 HPV-positive controls from a previous case-control study in Brazil. Codon-72 polymorphism was blindly analyzed in three different laboratories. We calculated age- and race-adjusted odds ratios (OR) and 95% confidence intervals (CI) using logistic regression for gauging the association between p53 polymorphism and cervical cancer risk. The proportions of the Arg/Arg, Arg/Pro, and Pro/Pro genotypes varied substantially among laboratories with Kappa coefficients in the 0.49-0.63 range. When disagreement between labs was allowed, the OR for the Arg/Arg genotype, compared to other forms, was as low as 1.5 (95% CI: 0.5-3. 9). In contrast, the OR increased to 8.0 (95% CI: 2.3-28.5) after exclusion of discordant genotypes. Restricting the comparison to HPV-positive controls increased the magnitude of the relation appreciably. After exclusion of all discordant diagnoses, the OR was 21.5 (95% CI: 3.4-137.8), whereas with disagreed genotypes the association was not significant (OR = 2.9, 95% CI: 0.7-11.9). Homozygous codon-72 p53-Arg apparently confers a higher susceptibility to HPV-associated cervical tumorigenesis. However, exposure misclassification consequent to inter-laboratory variation in protocols may affect the ability to detect the association.     

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.     

Association between the TP53 codon72 polymorphism and oral cancer risk and prognosis

The TP53 codon72 polymorphism has recently been extensively studied to determine the risk factor for carcinogenesis. However, there are few reports about the relationship between the TP53 codon72 polymorphism and oral cancer risk or post treatment prognosis. We evaluated the genotypic distribution of the TP53 codon72 polymorphism in 100 oral cancer cases and 271 non-cancer controls. There were no significant differences in the frequencies of the three genotypes (Arg/Arg, Arg/Pro, Pro/Pro) of the TP53 codon72 polymorphism between oral cancer cases and controls. However, stratifying by smoking status, we found that the adjusted odds ratio for non-smokers with the Pro/Pro genotype was significantly increased (adjusted OR = 2.70, 95% confidence interval = 1.07–6.82). We also found that the cases with the Pro/Pro genotype tended to have a shorter post-treatment survival compared with those with the Arg/Pro genotype (p = 0.06). Our results suggest the Pro/Pro genotype of the TP53 codon72 polymorphism increases oral cancer risk in non-smokers and worsens their prognosis.     

P53 codon 72 Arg/Pro polymorphism and glioma risk: an updated meta-analysis

P53 codon 72 Arg/Pro is a C/G variation upstream of the p53 gene on human chromosome 17p13. Many case–control studies have investigated the association between p53 codon 72 Arg/Pro polymorphism and glioma risk but provided inconsistent findings. To better understand the pathogenesis of glioma, we performed the current meta-analysis by pooling data from all available individual studies. According to the inclusion criteria, ten independent publications with 11 case–control studies were included into this meta-analysis. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to estimate the effect of p53 codon 72 Arg/Pro variant on the development of glioma. Overall, no appreciable correlation was observed among the total studies in all gene models (OR_{Pro allele vs. Arg allele}?=?1.04, 95 % CI?=?0.90–1.20, P _OR?=?0.581; OR_{Pro/Pro vs. Arg/Arg}?=?0.95, 95 % CI?=?0.80–1.14, P _OR?=?0.614; OR_{Pro/Arg vs. Arg/Arg}?=?1.01, 95 % CI?=?0.79–1.29, P _OR?=?0.993; OR_{Pro/Arg + Pro/Pro vs. Arg/Arg}?=?1.03, 95 % CI?=?0.82–1.29, P _OR?=?0.799; OR_{Pro/Pro vs. Arg/Arg + Pro/Arg}?=?1.02, 95 % CI?=?0.86–1.22, P _OR?=?0.785). In stratified analyses by ethnicity, source of controls, and glioma subtypes, the p53 codon 72 Arg/Pro polymorphism did not alter the risk for glioma in population-based, hospital-based, astrocytoma, and oligodendroglioma studies among Caucasian. Interestingly, the Pro/Pro genotype seemed to be negatively associated with the glioma risk among patients with glioblastoma (OR_{Pro/Pro vs. Arg/Arg}?=?0.68, 95 % CI?=?0.48–0.95, P _OR?=?0.026). Our study suggests that the polymorphism of p53 codon 72 Arg/Pro may play a protective role in the development of glioblastoma. The relationship of p53 codon 72 Arg/Pro polymorphism with the susceptibility to glioma needs further estimation by more individual studies with high quality across ethnicities.     

Evidence for an association of TP53 codon 72 polymorphism with breast cancer risk

BACKGROUND: A common Arg/Pro polymorphism at codon 72 of the TP53 gene has been investigated as a risk factor for cancer in different populations. So far, the results have been controversial. Our purpose was to investigate the association of this polymorphism with breast carcinoma in women from Southern Brazil, a high-risk area for breast cancer. METHODS: Blood samples collected from 118 women with primary breast carcinoma and from 202 female blood donors were analyzed through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. RESULTS: The relative frequency of each allele was 0.75 for Arg and 0.25 for Pro in patients with cancer, and 0.62 for Arg and 0.38 for Pro in normal controls (P < 0.001). The Arg/Arg genotype was significantly associated with an increased risk for breast cancer (OR 2.9; 95% CI 1.43-3.6; P < 0.002). No correlation between the genotype distribution and specific prognostic predictors for the disease outcome was observed. DISCUSSION: TP53 codon 72 polymorphism might be implicated in breast carcinogenesis, with the Arg/Arg genotype being associated with an increased susceptibility for this malignancy.     

P53 codon 72 polymorphism and correlation with ovarian and endometrial cancer in Greek women.

The polymorphism of codon 72 in the p53 tumour suppressor gene has been associated in the last decade with the risk of developing various neoplasias. An influence of this polymorphism on ovarian and endometrial cancer has also been suggested. We examined the genotype frequency of this polymorphism in archival samples from 56 patients with endometrial neoplasias and 51 patients with ovarian neoplasias. Cervical smears from 30 healthy, human papillomavirus (HPV)-negative women with normal cytology and colposcopy, served as control sample. Women with ovarian neoplasias, especially adenocarcinomas, had Arg/Arg more often than healthy controls [odds ratio (OR) 4.16 at P = 0.0058]. No statistically significant difference was found between women with endometrial cancer and controls. Differentiation of ovarian tumours did not appear to be associated in a statistically significant manner with the genotype, whereas a positive linear trend of Arg/Arg towards poor differentiation was noted in endometrial malignancies (mainly endometrioid adenocarcinomas). Our results suggest that homozygous arginine at codon 72 of p53 may represent a risk factor for developing ovarian malignancies and may affect the differentiation of endometrial cancer. Further studies need to be carried out in order to establish the clinical use of this polymorphism for risk assessment and possibly outcome prediction of ovarian and endometrial neoplasias.     

Association of Arg72Pro of P53 polymorphism with colorectal cancer susceptibility risk in Malaysian population

Background: Colorectal cancer (CRC) results from the interaction between environmental exposures and genetic predisposition factors. Aims: A case control study was designed and to investigate the genotype frequencies of P53Arg72Pro polymorphism in Malaysian CRC patients and healthy controls and to determine the associated risk of this polymorphism with CRC predisposition. Methods: In this case-control study, peripheral blood samples of 202 sporadic CRC patients and 201 normal controls were collected, DNA extracted and genotyped using the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) technique. Results: Genotype analysis showed the frequency of homozygous variant (Pro/Pro) genotype (21%) to be significantly higher in cases compared to controls (13%), (p=0.013). On examining the association between variant genotypes and CRC risk, the Pro/Pro homozygous variant genotype showed significantly higher risk association with CRC susceptibility (OR: 2.047, CI: 1.063-4.044, p=0.033). When stratified according to age, we observed that, individuals aged above 50 years and carriers of pro/pro genotype had significantly higher risk with OR: 3.642, CI: 1.166-11.378, p=0.026. Conclusions: Our results suggest that the codon 72 SNP which results in amino acid substitution of Arginine to Proline in cell cycle regulatory gene P53, is associated with sporadic CRC risk and carriers of Pro/Pro genotype and more than 50 years old may have high susceptibility.     

TP53 codon 72 polymorphism in radiation-associated human papillary thyroid cancer

The study investigated an association between the germline polymorphism at TP53 codon 72 and the development of papillary thyroid cancer (PTC) following exposure to radiation from the Chernobyl accident. TP53 genotype was examined in 48 pediatric/adolescent (age at diagnosis <18 years) and 68 adult post-Chernobyl patient with PTC, 53 adult patients with sporadic PTC and 313 healthy individuals from Russian-Ukrainian population. In addition, we evaluated loss of heterozygosity for TP53 and the allele expression ratio. The genotype of the patients was correlated with clinicopathological data. Arg TP53 homozygotes were found to be significantly underrepresented among adults with post-Chernobyl PTC, but not in children and adolescents when compared with sporadic PTC cases and the general population. In the tumors, cell transformation did not lead to allelic loss or biased TP53 allele expression in heterozygous individuals. None of TP53 genotypes specifically associated with tumor stage and morphology, however there were particular correlations with lymph node status in certain age groups of radiation-associated cases not seen in sporadic PTCs. The findings suggest TP53 allele combinations other than Arg/Arg may contribute to the risk of development of PTC in individuals exposed to radiation during their late childhood, adolescence or in young adulthood.