Association of glutathione S-transferase P1 gene polymorphism with the risk of small-cell carcinoma of lung cancer

Abstract

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of small-cell carcinoma of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of small-cell carcinoma of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Ten reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and small-cell carcinoma of lung cancer. The G allele and GG genotype were not associated with the susceptibility of risk of small-cell carcinoma in overall populations, East-Asians and Turkish population. However, there was an association between GG genotype with the risk of small-cell carcinoma in Caucasians. In conclusion, GG genotype was associated with the risk of small-cell carcinoma in Caucasian patients with lung cancer. However, GSTP1 A/G gene polymorphism is not associated with the susceptibility of small-cell carcinoma in overall populations, East-Asians and Turkish population.     

Association of glutathione S-transferase P1 gene polymorphism with the susceptibility of lung cancer

The conclusions of the published reports on the relationship between glutathione S-transferase P1 (GSTP1) gene polymorphism and the risk of lung cancer are still debated. GSTP1 is one of the important mutant sites reported at present. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of lung cancer. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Forty-four reports were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and lung cancer susceptibility, consisting of 12,363 patients with lung cancer and 13,948 controls. The association between GSTPI G allele and lung cancer risk was found in this meta-analysis (OR 1.08, 95?% CI 1.02–1.15, P?=?0.01). However, the GG genotype and AA genotype were not associated with the susceptibility of lung cancer. Furthermore, there was no association between GSTP1 A/G gene polymorphism and the risk of lung cancer in Caucasians, and East-Asians. In conclusion, GSTP1 G allele is associated with the lung cancer susceptibility. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of lung cancer should be performed in the future.     

A meta-analysis of the association of glutathione S-transferase P1 gene polymorphism with the susceptibility of breast cancer

Glutathione S-transferase P1 (GSTP1) is one of the important mutant sites for the cancer risk at present. The conclusions of the published reports on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of breast cancer. The association reports were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 35 investigations were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and breast cancer susceptibility, consisting of 40,347 subjects (18,665 patients with breast cancer and 21,682 controls). The association between GSTP1 A/G gene polymorphism and breast cancer risk was not found for overall population, Caucasians and Africans. Interestingly, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer in Asians (G allele: OR = 1.10, 95 % CI: 1.04–1.17, P = 0.001; GG genotype: OR = 1.36, 95 % CI: 1.14–1.62, P = 0.0008; AA genotype: OR = 0.92, 95 % CI: 0.85–0.98, P = 0.02). Furthermore, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer for the analysis of the controls from hospital. In conclusion, GSTP1 A/G gene polymorphism is associated with the breast cancer susceptibility in Asians. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer should be performed in further.     

GSTP1 Ile105Val polymorphism is associated with lung cancer risk among Asian population and smokers: An updated meta-analysis

Many studies have examined the association between the GSTP1 Ile105Val (rs 1695) gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case–control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 42 studies, comprising 12,304 lung cancer cases and 15,729 controls were included. Overall, for G allele carriers (GA + GG) versus homozygote AA, the pooled OR was 1.05 (95 % CI 0.99–1.10 P = 0.092 for heterogeneity), for GG versus AA the pooled OR was 1.04 (95 % CI 0.96–1.12 P = 0.084 for heterogeneity). In the stratified analysis by ethnicity, gender, histological types of lung cancer and smoking status, a significant association was found in Asians and smokers, not in Caucasian or mixed population, Male, Female population, lung AC, SCC, SCLC or non-smokers. Publication bias was found by using the funnel plot and Egger’s test. Overall, there is no evidence showing a significant correlation between GSTP1 Ile105Val gene polymorphism and lung cancer risk in overall population, however stratified analysis by ethnicity, histology, gender and smoking status, it correlate with increased lung cancer susceptibility among Asians and smokers.     

Glutathione S-transferase P1 gene polymorphism and bladder cancer susceptibility: an updated analysis

Studies investigating the association between glutathione S-transferase P1 (GSTP1) gene polymorphism and bladder cancer (BC) risk have reported conflicting results. In order to clarify the effect of GSTP1 polymorphism on the BC susceptibility, we conducted an updated system review of published epidemiology studies to provide more precise evidence. We performed a systematic search of PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI). 20 studies with 4,428 BC cases and 5,457 controls were identified. The combined analyses based on all studies showed that there was a significant difference in the genotype distribution in GSTP1(A313G) polymorphism between BC cases and controls not only in Asians (GG vs. AA?+?AG, OR?=?1.59, 95?% CI?=?1.01?C2.51) but also in Caucasians (GG vs. AA?+?AG, OR?=?1.51, 95?% CI?=?1.11?C2.06). Upon stratification for smoking status, we observed no statistically significant difference in genotype distribution of GSTP1 in ever-smokers. Combination of the high-risk genotypes (GSTM1 null?+?GSTT1 null?+?GSTP1 313 A/G or G/G) demonstrated further increase in the BC risk (OR?=?6.64, 95?%CI?=?3.63?C12.16). This meta-analysis suggests that GSTP1 313 G/G polymorphism is a strong predisposing risk factor for BC.     

A80G polymorphism of reduced folate carrier 1 (<Emphasis Type="Italic">RFC1</Emphasis>) gene and head and neck squamous cell carcinoma etiology in Brazilian population

Reduced folate carrier is an essential folate transporter and the A80G polymorphism in reduced folate carrier 1 gene (rs1051266) has been shown to be associated with alterations in folate metabolism and consequently cancer development. We evaluated the association of this polymorphism with head and neck squamous cell carcinoma risk in a case–control study of 322 head and neck carcinoma patients and 531 individuals without cancer in a Brazilian population and association of this polymorphism with clinical histopathological parameters, and gender and lifestyle factors. The PCR-RFLP technique was used to genotype the polymorphism and multiple logistic regression was used for comparation between the groups and for interaction between the polymorphism and risk factors and clinical histopathological parameters. We observed association between the RFC1 A80G polymorphism and the risk of this disease. Male gender, tobacco habit and RFC1 AG or GG genotypes may be predictors of this disease (P < 0.05). The genotype, 80AG or GG was associated with for >50 years, male gender and non alcohol consumption (P ≤ 0.05). The polymorphism did not show any association with the primary site, aggressiveness, lymph node involvement or extension of the tumor. In conclusion tobacco and male gender are associated with etiology of this disease and our data provide evidence that supports an association between the RFC1 A80G polymorphism and head and neck squamous cell carcinoma risk, male gender, alcohol non consumption and age over 50 years. However, further studies of folate and plasma concentrations may contribute to the better understanding of the factors involved in the head and neck squamous cell carcinoma etiology.     

CCND1 G870A polymorphism interaction with cigarette smoking increases lung cancer risk: meta-analyses based on 5008 cases and 5214 controls

Evidence indicates CCND1 G870A polymorphisms as a risk factor for a number of cancers. Increasing studies have been conducted on the association of CCND1 G870A polymorphism with lung cancer risk. However, the results were controversial. The aim of the present study was to derive a more precise estimation of the relationship. Meta-analyses examining the association between CCND1 G870A polymorphism and lung cancer were performed. Subgroup analyses regarding ethnicity, smoking status, histological types and source of controls were also implemented. All eligible studies for the period up to May 2012 were identified. The overall data from ten case–control studies including 5,008 cases and 5,214 controls indicated that variant A allele may have an association with increased lung cancer risk (AA vs GG: OR = 1.21; 95 % CI = 1.08–1.36, dominant model: OR = 1.09; 95 % CI = 1.00–1.19, recessive model: OR = 1.23; 95 % CI = 1.01–1.49). In the subgroup analysis by ethnicity, A allele may elevate lung cancer risk among Asians but not Caucasians or Mixed ethnicities. In smoking status subgroup, A allele was shown to associate with increased lung cancer risk among smokers but not non-smokers. In the subgroup analysis by histological types, increased cancer risks were shown in adenocarcinoma but not squamous cell carcinoma, under the homozygote comparison and recessive models. Collectively, the results of the present study suggest that CCND1 G870A polymorphism might be a low-penetrant risk factor for lung cancer, particularly among Asians and smokers. Moreover, homozygous AA alleles might have a correlation with increased lung adenocarcinoma susceptibility.     

Detection of human papillomavirus in non-small cell lung carcinoma by polymerase chain reaction

Human papillomavirus (HPV) infection is one of the risk factors contributing to the pathogenesis of lung cancer. The aim of the study was to determine the presence of HPV in non-small cell carcinomas of the lung. The study included 40 tumors: 22 squamous cell carcinomas, 13 adenocarcinomas and 5 large cell carcinomas. HPV was found in 4 cases (10%). High risk HPV was present in 3 tumors: in one squamous cell carcinoma, one large cell carcinoma and one adenocarcinoma, while low risk HPV was detected in one adenocarcinoma.     

Impact of glutathione transferase M1, T1, and P1 gene polymorphisms in the genetic susceptibility of North Indian population to renal cell carcinoma

In this study, we investigated the association of GSTP1, GSTM1, and GSTP1 genetic variants with renal cell carcinoma (RCC) among North Indian patients. The difference in frequency of the GSTT1 null genotype between cases and control subjects was statistically significant (active ver. null, odds ratio [OR]=0.368; confidence intervals [CI] 95%=0.243-0.557, p=0.001). The differences in the frequency of GSTP1 genotypes were statistically significant (AA ver. AG/GG, OR=1.879; CI 95%=0.355-0.797, p=0.002). Higher allelic frequency of the GSTP1 G allele was associated with RCC cases (G ver. A allele, OR=1.534; 95% CI=1.159-2.030, p=0.003). The gene-gene interaction in terms of three-way combination of GSTM1 null, GSTT1 null, and GSTP1 (AG/GG) resulted in 4.5-fold increase in RCC risk (OR=4.452; 95% CI=2.220-9.294). Similarly, our study revealed that GST polymorphism might be a vital determinant of advancement to higher pathological stages and histological grades of RCC. Our findings suggest that genetic variability in members of the GST gene family may be associated with an increased susceptibility to RCC and its progression.     

Association of Megsin gene polymorphism with IgA nephropathy risk

Abstract

This meta-analysis was conducted to assess the association of Megsin 2093C/T, 2180C/T, C25663G gene polymorphism with the risk of IgA nephropathy (IgAN). The association literatures were identified from PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on 1 January 2014, and eligible reports were recruited and synthesized. Seven eligible reports were recruited into this meta-analysis for the association of Megsin 2093C/T, 2180C/T, C25663G gene polymorphism with IgAN risk. In this meta-analysis, the association of Megsin 2093C/T TT genotype with IgAN risk in Asians was found. Interestingly, Megsin C25663G G allele and GG genotype were associated with the risk of IgAN in Asian population. However, Megsin 2180C/T gene polymorphism was not associated with IgAN risk in Asians. In conclusion, Megsin 2093C/T TT genotype, and C25663G G allele and GG genotype were associated with the risk of IgAN in Asian population. However, more studies should be performed in the future to confirm this association.     

Immunohystochemical expression of cancer/testis antigens (MAGE-A3/4, NY-ESO-1) in non-small cell lung cancer: the relationship with clinical-pathological features

The aim of this study was to explore the expression of cancer/testis tumor associated antigens (C/T TAAs) MAGE-A 3/4 and NY-ESO-1 in lung squamous cell carcinoma and adenocarcinoma, and to evaluate their association with the standard clinical-pathological features of surgically treated lung cancer patients. The study included 80 patients with non-small cell lung cancer (40 adenocarcinomas, 40 squamous cell carcinomas) who had undergone surgery in the period between 2002 and 2005. The MAGE-A3/4 and NY-ESO-1 antigen expression was analyzed immunohistochemically (IHC). The results showed MAGE-A3/4 and NY-ESO-1 positive staining in 65.1% and 23.3% of squamous cell carcinomas and 18.9% and 10.8% of adenocarcinomas, respectively. A statistically higher MAGE-A3/4 expression was observed in planocellular bronchial carcinoma (p < 0.001), while no difference was found in the expression of NY-ESO-1 in adenocarcinoma and planocellular carcinoma (p = 0.144). A significant association was found between the MAGE-A3/4 expression and presence of tumor necrosis in squamous cell cancer specimens (p = 0.001), but not in adenocarcinoma (p = 0.033). A statistically significant association was noted between the NY-ESO-1 expression and positive hilar and mediastinal lymph nodes in adenocarcinoma (p = 0.025) whereas it was not the case in squamous cell carcinoma. Non-small cell lung cancer frequently expresses cancer/testis tumor associated antigens. Our results demonstrate that the MAGE-A3/4 and NY-ESO-1 expression was significant associated with prognostic factors of poor outcome of disease (presence of tumor necrosis and lymph node metastasis). As C/T antigens are important for inducing a specific immune reaction in lung cancer patients, there is an intention to form a subgroup of patients in the future, whose treatment would be enhanced by specific immunotherapy based on the observed scientific results.     

Association of vitamin D receptor gene polymorphism with the risk of lung cancer: a meta-analysis

Abstract

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of lung cancer from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR TaqI (rs731236), BsmI (rs1544410) and ApaI (rs7975232) gene polymorphism and the risk of lung cancer using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 December 2013, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR gene polymorphism with lung cancer susceptibility. In the meta-analysis for ApaI gene polymorphism, AA genotype was associated with the risk of lung cancer in Asians. In the meta-analysis for BsmI gene polymorphism, B allele, BB genotype and bb genotype were associated with lung cancer in Asians, and B allele bb genotype were associated with lung cancer risk in overall populations; furthermore, bb genotype was associated with lung cancer risk in Caucasians. In the meta-analysis for TaqI gene polymorphism, t allele and TT genotype were associated with lung cancer in overall populations and in Caucasians. In conclusion, B allele bb genotype t allele and TT genotype were associated with lung cancer risk in overall populations. AA genotype, B allele, BB genotype and bb genotype were associated with the risk of lung cancer in Asians. Furthermore, bb genotype t allele and TT genotype was associated with lung cancer risk in Caucasians. However, more studies should be conducted to confirm it.     

Current evidence on the relationship between CYP1B1 polymorphisms and lung cancer risk: a meta-analysis

The association between single-nucleotide polymorphisms (SNPs) of the CYP1B1 gene and lung cancer risk is still ambiguous. In this meta analysis, we assessed 10 case–control studies included 7,067 cases and 9,374 controls of the association between CYP1B1 SNPs of Leu432Val (rs1056836, 432C>G), Asn453Ser (rs1800440, 453A>G), Ala119Ser (rs1056827, 119G>T), Arg48Gly (rs10012, 48C>G) and the risk of lung cancer. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between the polymorphism and lung cancer risk under codominant model, dominant model and additive model respectively. Although there were limitations, this meta analysis indicated that individuals with 432GG genotype had a 39.7% higher risk of having lung cancer than those with the 432CC genotype, and individuals with the 432G allele had a 26.3% increased risk as well. An increased risk of lung cancer of 2.13 fold was observed in individuals with 119TT genotype. For Arg48Gly, individuals with 48GG genotype had a significantly increased risk of lung cancer compared with individuals with 48CC (OR 3.859; 95% CI 2.536–5.87). Elevated risk of lung cancer were observed in dominant model (OR 2.115; 95% CI 1.653–2.705) as well. The risk of lung cancer was elevated as the frequency of G allele increased in additive model (P = 0.000). For individuals with the polymorphism at codon 453, no evidence of such association was observed. Furthermore, a possible association between the CYP1B1 polymorphism at codon 432 and the lung cancer could be detected in individuals of Caucasian origin, while a negative association was suggested in Asians and African-Americans. An increased lung cancer risk was also found in women with polymorphism at codon 453. These results are supportive for the hypothesis that the CYP1B1 432GG, 119TT and 48GG genotypes are low-penetrance risk factors for developing lung cancer, and further studies are needed to validate these associations.     

Glutathione S-transferase T1 gene deletion polymorphism and lung cancer risk in Chinese population: A meta-analysis

Genetic variations in metabolic genes are considered to modulate metabolic process of carcinogens and are suggested to be related to cancer risk. However, epidemiological results are not always consistent. In this meta-analysis, we evaluated reported studies of association between polymorphism of glutathione S-transferase T1 gene (GSTT1) and the risk of lung cancer in Chinese population. We found an increased lung cancer risk among subjects carrying GSTT1 null genotype [odds ratio (OR) = 1.36, 95 percent confidence interval (95% CI): 1.09–1.69], using 1625 cases and 2188 controls from 11 studies. We also observed an increased risk of lung cancer among null genotype carriers in squamous cell carcinoma and andenocarcinoma, and on the basis of population control in stratified analyses. The meta-analysis suggests that GSTT1 deletion polymorphisms may have an effect on the susceptibility of lung cancer in Chinese population, and a study with the larger sample size is needed to further evaluate gene–gene and gene–environment interaction on GSTT1 deletion polymorphisms and lung cancer risk in Chinese population.     

High frequency of p16 promoter methylation in non-small cell lung carcinomas from Chile

The inactivation of tumour suppressor genes by aberrant methylation of promoter regions has been described as a frequent event in neoplasia development, including lung cancer. The p16 gene is a tumour suppressor gene involved in the regulation of cell cycle progression that has been reported to be inactivated by promoter methylation in lung carcinomas at variable frequencies around the world in a smoking habit dependent manner. The purpose of this study was to investigate the methylation status of the promoter region of the p16 gene in 74 non-small cell lung carcinomas from Chile. The frequency of p16 gene inactivation by promoter methylation was determined as 79.7% (59/74). When we considered histological type, we observed that p16 promoter methylation was significantly higher in squamous cell carcinomas (30/33, 91%) compared with adenocarcinomas (21/30, 70%) (p=0.029). In addition, no association between p16 promoter methylation and gender, age or smoking habit was found (p=0.202, 0.202 and 0.147 respectively). Our results suggest that p16 promoter hypermethylation is a very frequent event in non-small cell lung carcinomas from Chile and could be smoking habit-independent.     

A meta-analysis of the relationship between glutathione S-transferases gene polymorphism and hepatocellular carcinoma in Asian population

The results from the published studies on the association between glutathione S-transferases (GST) gene polymorphism and hepatocellular carcinoma (HCC) in Asian population are still conflicting. GSTM1, GSTT1 and GSTP1 are the mainly mutant sites reported at present. This meta-analysis was performed to evaluate the relationship between GST gene polymorphism and HCC risk in Asians. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on February 1, 2012, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95?% confidence intervals (CI) were also calculated. Twenty-five investigations were identified for the analysis of association between polymorphic deletion of GSTM1 and HCC, consisting of 3,547 patients with HCC and 6,132 controls. There was a marked association between GSTM1 null genotype and HCC susceptibility (OR 1.48, 95?% CI 1.19–1.85, P?=?0.0004). GSTM1 null genotype was associated with HCC risk in Chinese. Furthermore, null genotype of GSTT1 was associated with HCC susceptibility in Asians. For the GSTM1–GSTT1 interaction analysis, the dual null genotype of GSTM1/GSTT1 was significantly associated with HCC susceptibility in Asian population. However, GSTP1 ile105?val gene polymorphism was not associated with HCC risk in Asian population. In conclusion, GSTM1/GSTT1 null genotype is associated with the HCC susceptibility. However, GSTP1 gene polymorphism is not associated with HCC risk.     

Association of vitamin D receptor gene polymorphism with the risk of renal cell carcinoma: a meta-analysis

Abstract

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of renal cell carcinoma from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and Fok1 (rs2228570) gene polymorphism and the risk of renal cell carcinoma using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Five reports were recruited into this meta-analysis for the association of VDR gene polymorphism with renal cell carcinoma susceptibility. In this meta-analysis, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, VDR ApaI, BsmI, TaqI, and Fok1 gene polymorphism were not associated with the risk of renal cell carcinoma in overall populations and in Caucasians. In conclusion, the ApaI AA genotype, BsmI BB genotype, Fok1 f allele, and Fok1 FF genotype were associated with the risk of renal cell carcinoma in Asians. However, more studies should be conducted to confirm it.     

XRCC1 gene polymorphisms and lung cancer susceptibility: a meta-analysis of 44 case–control studies

X-ray repair cross-complementing group 1 gene (XRCC1) has been implicated in risk for lung cancer. However, the results from different studies remain controversial. In this meta-analysis, we have assessed 44 published case-control studies regarding associations of lung cancer risk with three common polymorphisms, codon 194, codon 280 and codon 399, and -77 T?>?C in the promoter region of XRCC1. The results in total population showed that the risk for lung cancer was increased among the variant homozygote Trp/Trp of codon 194 polymorphism, compared with the wild type Arg/Arg (OR: 1.19; 95?% CI 1.01-1.39), and the variant genotype CC of -77 T?>?C polymorphism showed a significantly increased risk of developing lung cancer, compared to wild-type genotype TT (OR: 1.91; 95?% CI 1.24-2.94). However, no associations were found between lung cancer risk and codon 280, codon 399. In the subgroup analyses by ethnicity, the OR for the variant homozygote Trp/Trp of codon 194 was 1.21(95?% CI 1.02-1.43) for Asian. When stratified by source of control, we found a protective effect of codon 194 Arg/Trp genotype (OR: 0.87; 95?% CI 0.77-0.98) and risk effect of codon 399 combined Arg/Gln?+?Gln/Gln variant genotype (OR: 1.09; 95?% CI 1.01-1.18) for lung cancer on the basis of hospital control. Subgroup analyses by histological types of lung cancer indicated that the heterozygote Arg/Trp in codon 194 could decrease and the combined variant genotype Arg/Gln?+?Gln/Gln in codon 399 could increase the risk of non-small cell lung cancer (OR: 0.69; 95?% CI 0.57-0.85 and OR: 1.14; 95?% CI 1.04-1.24). In conclusion, this meta-analysis has demonstrated that codon 194, codon 399 and -77 T?>?C polymorphisms of XRCC1 gene might have contributed to individual susceptibility to lung cancer. To further evaluate effect of XRCC1 polymorphisms, gene-gene interaction and gene-environment interaction on lung cancer risk, a single large sample size study with thousands of subjects is required to get conclusive results.     

Transferase S-glutathione class pi gene (GSTP1) polymorphism in thyroid cancer patients

INTRODUCTION: One of the potential genes which can increase the risk of cancer is GSTP1 gene. It encodes enzyme called glutathione S-transferase pi class, which is involved in the detoxification of a variety of potential carcinogenic compounds. Polymorphism in this gene can cause the amino acid substitution. This substitution, close to the substrate binding site, changes the enzymatic activity for particular substrates and subsequently increases the risk of carcinogenesis. The aim of this study was to evaluate the function of GSTP1 polymorphism in thyroid cancer and possible association between GSTP1 polymorphism and age at diagnosis. MATERIAL AND METHODS: 103 patients with differentiated thyroid cancer (DTC) and 53 individuals from control group were examined using PCR-RFLP. RESULTS: Statistically insignificant association of studied polymorphisms with thyroid cancer was observed. Comparison of allele frequency between cases and control groups revealed the presence of risk alleles. For the first polymorphism Ile OR = 1.257; 95% CI [0.792-1.997] (p = 0.332), and for the second one Val OR = 1.283; 95% CI [0.6260-2.631] (p = 0.495). The presence of Val/Val (c.313A>G) led to a significant earlier age of onset as compared with other genotypes (p < 0.05). Mean age at diagnosis for Val/Val genotype was 41.1 +/- 15.2, and for Ile/Val + Ile/Ile reached 48.9 +/- 13.2. There was no association between age and genotype for c.341C>T polymorphism. CONCLUSIONS: Statistically insignificant association of GSTP1 gene polymorphism with thyroid cancer was observed in studied group of patients. The Val/Val genotype for c.313A>G polymorphism led to earlier age of tumour diagnosis as compared with other genotypes.     

Association between the p73 exon 2 G4C14-to-A4T14 polymorphism and cancer risk: a meta-analysis

The TP53 homolog p73 is structurally and functionally similar to TP53 and plays an important role in modulating cell-cycle control, apoptosis, and cell growth. G4C14-to-A4T14 is the most commonly studied polymorphism of this gene for its association with risk of cancers, but the results are confusing rather than conclusive. We performed a meta-analysis using 21 eligible studies with a total of 7581 patients and 10,413 controls to summarize the data for an association between the p73 G4C14-to-A4T14 polymorphism and cancer risk. Compared with the common GC/GC genotype, the AT carriers (AT/GC, AT/AT) had a 1.18-fold elevated risk of cancer (95% confidence interval [CI]=1.11-1.25, p<0.00001) in a dominant genetic model as estimated in a fixed effect model. The effect of the G4C14-to-A4T14 polymorphism was further evaluated through stratification analysis. In four lung cancer studies, the variant genotypes had a significantly increased risk of lung cancer (odds ratio [OR]=1.16, 95% CI=1.04-1.28, p=0.005). Similar phenomena were also found in two squamous cell carcinoma of the head and neck studies (OR=1.32, 95% CI=1.12-1.56, p=0.0010), two oral cancer studies (OR=1.57, 95% CI=1.26-1.95, p<0.0001), and three colorectal cancer studies (OR=1.23, 95% CI=1.01-1.50, p=0.04). Increased risk of cancer associated with G4C14-to-A4T14 variant genotypes was pronounced in Caucasians (OR=1.21, 95% CI=1.11-1.31, p<0.00001), the Japanese population (OR=1.24, 95% CI=1.01-1.52, p=0.04), and the Korean population (OR=1.27, 95% CI=1.07-1.52, p=0.007). Our meta-analysis suggests that the p73 G4C14-to-A4T14 polymorphism genotypes (GC/AT+AT/AT) may be associated with an increased risk of cancer in most cancer types and ethnicities.