Sulfotransferase SULT1A1 Arg213His Polymorphism with Cancer Risk: A Meta-Analysis of 53 Case-Control Studies

Background

The SULT1A1 Arg213His (rs9282861) polymorphism is reported to be associated with many kinds of cancer risk. However, the findings are conflicting. For better understanding this SNP site and cancer risk, we summarized available data and performed this meta-analysis.

Methods

Data were collected from the following electronic databases: PubMed, Web of Knowledge and CNKI. The association was assessed by odd ratio (OR) and the corresponding 95% confidence interval (95% CI).

Results

A total of 53 studies including 16733 cancer patients and 23334 controls based on the search criteria were analyzed. Overall, we found SULT1A1 Arg213His polymorphism can increase cancer risk under heterozygous (OR = 1.09, 95% CI = 1.01–1.18, P = 0.040), dominant (OR = 1.10, 95% CI = 1.01–1.19, P = 0.021) and allelic (OR = 1.08, 95% CI = 1.02–1.16, P = 0.015) models. In subgroup analyses, significant associations were observed in upper aero digestive tract (UADT) cancer (heterozygous model: OR = 1.62, 95% CI = 1.11–2.35, P = 0.012; dominant model: OR = 1.63, 95% CI = 1.13–2.35, P = 0.009; allelic model: OR = 1.52, 95% CI = 1.10–2.11, P = 0.012) and Indians (recessive model: OR = 1.93, 95% CI = 1.22–3.07, P = 0.005) subgroups. Hospital based study also showed marginally significant association. In the breast cancer subgroup, ethnicity and publication year revealed by meta-regression analysis and one study found by sensitivity analysis were the main sources of heterogeneity. The association between SULT1A1 Arg213His and breast cancer risk was not significant. No publication bias was detected.

Conclusions

The present meta-analysis suggests that SULT1A1 Arg213His polymorphism plays an important role in carcinogenesis, which may be a genetic factor affecting individual susceptibility to UADT cancer. SULT1A1 Arg213His didn''t show any association with breast cancer, but the possible risk in Asian population needs further investigation.     

SULT1A1 Arg213His polymorphism, smoked meat, and breast cancer risk: a case-control study and meta-analysis

SULT1A1 is involved in both detoxification of estrogens and bioactivation of carcinogens in smoked meat. SULT1A1 Arg213His polymorphism's effect on breast cancer risk is still unclear. We recruited 400 case-control pairs to investigate the association between SULT1A1 genotypes and breast cancer risk, and the combined effect of SULT1A1 polymorphism and daily intake of smoked meat. Participants were questioned about their dietary habits and other risk factors, and their SULT1A1 genotypes were determined. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated by multivariable unconditional logistic regression. We also performed a meta-analysis of relevant published studies to test these associations. In the case-control study, no significant associations were observed between SULT1A1 polymorphism and breast cancer risk. In the meta-analysis, SULT1A1 His/His genotype slightly increased risk among both overall and postmenopausal women (OR(pooled-overall)=1.12, 95% CI: 1.02-1.24; OR(pooled-post)=1.17, 95% CI: 1.03-1.32). A larger positive association was observed in Asian populations (OR(pooled-Asian)=2.01, 95% CI: 1.24-3.26). In our case-control study, high energy-adjusted daily intake of smoked meat was significantly associated with breast cancer risk in overall, pre- and postmenopausal women (aORs: 2.31-3.13, OR 95% CIs exclude 1). High smoked meat intake interacted positively with the His variant allele (all γ>1). These results correlated with those of the meta-analysis (γ(pooled-overall)=1.27). The SULT1A1 His/His genotype may increase the risk of breast cancer among Asian women, and dietary exposure to heterocyclic amines and polycyclic aromatic hydrocarbons, along with the SULT1A1 His/His variant genotype, may synergistically increase the risk of breast cancer.     

Effect of LEPR Gln223Arg polymorphism on breast cancer risk in different ethnic populations: a meta-analysis

Leptin and leptin receptor have been implicated in processes leading to breast cancer initiation and progression. An A to G transition mutation in codon 223, in exon 6 of the leptin receptor gene (LEPR) can result in glutamine to arginine substitution (Gln223Arg). A variety of case–control studies have been published evaluating the association between LEPR Gln223Arg polymorphism and breast cancer. However, published studies have yielded contradictory conclusions. This meta-analysis enrolled eight studies to estimate the overall risk of LEPR Gln223Arg polymorphism associated with breast cancer. The pooled ORs were performed for codominant model (Arg/Arg versus Gln/Gln; Arg/Gln versus Gln/Gln), dominant model (Arg/Arg + Arg/Gln versus Gln/Gln), recessive model (Arg/Arg versus Arg/Gln + Gln/Gln). Overall significantly elevated breast cancer risk was found for recessive model (OR 1.32, 95% CI 1.03–1.69) and for genotype Arg/Gln versus Gln/Gln (OR 1.16, 95% CI 1.01–1.34). In the stratified analysis by ethnicity, significantly increased risks were also found among Africans for genotype Arg/Arg versus Gln/Gln: OR 1.86, 95% CI 1.28–2.71, Arg/Gln versus Gln/Gln: OR 1.48, 95% CI 1.10–1.99, dominant model: OR 1.60, 95% CI 1.21–2.11 and recessive model: OR 1.48, 95% CI 1.07–2.05; for Asians, Arg/Arg versus Gln/Gln: OR 6.79, 95% CI 3.42–13.47 and dominant model: OR 2.03, 95% CI 1.42–2.90. However, no significantly increased risk was found among Europeans for all genetic models. In conclusion, the LEPR 223Arg is a low-penetrant risk for developing breast cancer, especially for black African women.     

Polymorphisms of XRCC1 and gastric cancer susceptibility: a meta-analysis

Studies investigating the association between X-ray repair cross-complementing gene 1 (XRCC1) polymorphisms and gastric cancer (GC) risk have reported conflicting results. We performed a meta-analysis of published case–control and cohort studies to better compare results between studies. Published literature from PubMed, EMBASE, and China National Knowledge Infrastructure were retrieved. 18 studies with 3,915 GC cases and 6,759 controls were selected. For XRCC1 Arg194Trp polymorphism, we only found the Trp/Trp genotype carriers might be at high risk of GC (TT vs. CC+CT: OR = 1.31, 95%CI = 1.04–1.65). When stratifying for ethnicity, the results showed there was a significant difference in genotype distribution between GC cases and controls among Asians (especially, in Chinese population), but not among Caucasians. When stratifying for control sources, significant association between Arg194Trp polymorphism and GC risk was only observed in the hospital-based controls’ subgroup (TT vs. CC+CT: OR = 1.45, 95%CI = 1.13–1.87). Additionally, no significant association was detected in the gastric cardia cancer’s subgroup. The results of the overall meta-analysis did not suggest any association between Arg280His/Arg399Gln polymorphisms and GC susceptibility for all genetic models. There was no evidence for the association between these two gene polymorphisms and GC risk in subgroup analyses based on study design, ethnicity, country, tumor location, Helicobacter pylori infection and the Lauren’s classification of GC. In conclusion, XRCC1 Arg194Trp homozygous mutant genotype (Trp/Trp) was found to be associated with increased risk of GC.     

Polymorphisms in <Emphasis Type="Italic">RAD51, XRCC2</Emphasis> and <Emphasis Type="Italic">XRCC3</Emphasis> genes of the homologous recombination repair in colorectal cancer—a case control study

XRCC2 and XRCC3 proteins are structurally and functionally related to RAD51 which play an important role in the homologous recombination, the process frequently involved in cancer transformation. In our previous work we show that the 135G>C polymorphism (rs1801320) of the RAD51 gene can modify the effect of the Thr241Met polymorphism (rs861539) of the XRCC3 gene. We tested the association between the 135G>C polymorphism of the RAD51 gene, the Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism (rs3218536) of the XRCC2 gene and colorectal cancer risk and clinicopathological parameters. Polymorphisms were evaluated by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) in 100 patients with invasive adenocarcinoma of the colon and in 100 sex, age and ethnicity matched cancer–free controls. We stratified the patients by genotypes, tumour Duke’s and TNM stage and calculated the linkage of each genotype with each stratum. Carriers of Arg188Arg/Me241tMet, His188His/Thr241Thr and His188His/G135G genotypes had an increased risk of colorectal cancer occurrence (OR 5.70, 95% CI 1.10–29.5; OR 12.4, 95% CI 1.63–94.9; OR 5.88, 95% CI 1.21–28.5, respectively). The C135C genotype decreased the risk of colorectal cancer singly (OR 0.06, 95% CI 0.02–0.22) as well as in combination with other two polymorphisms. TNM and Duke’s staging were not related to any of these polymorphisms. Our results suggest that the 135G>C polymorphism of the RAD51 gene can be an independent marker of colorectal cancer risk. The Thr241Met polymorphism of the XRCC3 gene and the Arg188His polymorphism of the XRCC2 gene can modify the risk of colorectal cancer.     

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.     

CDH1 promoter polymorphism and stomach cancer susceptibility

The relationship of stomach cancer susceptibility and the presence of E-cadherin (CDH1) promoter −160 C/A polymorphism had been reported with conflicting results. To further explore the association of this polymorphism with stomach cancer susceptibility, we performed an extensive search of relevant studies and carried out a meta-analysis to obtain a more precise estimate. A total of 16 studies including 2,611 cases and 3,788 controls were involved in this meta-analysis. When all studies involved, the meta-analysis results suggest no statistically significant association between CDH1 −160 C/A polymorphism and stomach cancer risk (CA vs. CC: OR = 1.01, 95% CI: 0.85–1.19; AA vs. CC: OR = 1.05, 95% CI: 0.75–1.46; dominant model: OR = 1.02, 95% CI: 0.86–1.20; recessive model: OR = 1.04, 95% CI: 0.76–1.41). When subgroup analyses were performed by ethnicity, the A-allele carriers conferred a decreased stomach cancer risk in Asians (AA vs. CC: OR = 0.67, 95% CI: 0.47–0.96; dominant model: OR = 0.85, 95% CI: 0.72–0.99), but no statistically significant association was found in Caucasians. In conclusion, this meta-analysis suggests that CDH1 −160 A-allele may play a protective role of stomach cancer development in Asians but not in Caucasians.     

A meta-analysis of β1-adrenergic receptor gene polymorphisms in idiopathic dilated cardiomyopathy

Published data on the association between β₁-adrenergic receptor gene polymorphisms and idiopathic dilated cardiomyopathy (IDCM) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 12 case–control studies including 2642 cases and 3136 controls provided data on the association between β₁-adrenergic receptor gene polymorphisms and susceptibility to IDCM. Overall, no significantly elevated risk was associated with Arg389Gly polymorphisms for all genetic models. In the subgroup analysis by ethnicity, no statistically increased risk was found for Gly389Gly versus Arg389Arg (OR 0.73; 95% CI 0.54–0.99; P _h = 0.35) and Gly389Gly versus Arg389Arg + Arg389Gly (OR 0.75; 95% CI 0.55–1.01; P _h = 0.52) among Europeans. Meanwhile, significantly increased risk was found among Asians based on the relatively small sample size. Further, significantly elevated IDCM risk was associated with Ser49Gly polymorphisms for all genetic models. When stratified by ethnicity, statistical association was found among Asians for Gly49Gly versus Ser49Ser (OR 4.56; 95% CI 1.36–15.23; P _h = 0.10) and Gly49Gly versus Ser49Ser + Ser49Gly (OR 4.49; 95% CI 1.33–15.15; P _h = 0.12), but not among Europeans. In summary, this meta-analysis suggests that no statistically increased risk was found between β₁-adrenergic receptor gene polymorphisms and susceptibility to IDCM among Europeans.     

<Emphasis Type="Italic">TP53</Emphasis> codon 72 polymorphism and colorectal cancer susceptibility: a meta-analysis

Colorectal cancer constitutes a significant proportion of the global burden of cancer morbidity and mortality. A number of studies have been conducted to explore whether TP53 codon 72 polymorphism is associated with colorectal cancer susceptibility. However, controversial results were obtained. In order to derive a more precise estimation of the relationship, we systematically searched Medline, Google scholar, and Ovid database for studies reported before May 2010. A total of 3603 colorectal cancer cases and 5524 controls were included. TP53 codon 72 polymorphism was not associated with colorectal cancer risk in all genetic models (for dominant model: OR = 0.99, 95% CI: 0.86–1.15; for recessive model: OR = 1.00, 95% CI: 0.81–1.23; for Arg/Pro vs. Arg/Arg: OR = 1.00, 95% CI: 0.87–1.15; for Pro/Pro vs. Arg/Arg: OR = 0.97, 95% CI: 0.76–1.25). In the subgroup analyses by ethnic groups and sources of controls, no significant associations were found in all models. Taken together, this meta-analysis suggested that the biologically usefulness of TP53 codon 72 polymorphism as a selection marker in colorectal cancer susceptibility may be very limited.     

APE1 Asp148Glu gene polymorphism and lung cancer risk: a meta-analysis

Many studies have examined the association between the APE1 T1349G (Asp148Glu) gene polymorphisms 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, Embase, Web of Science, and CNKI database was searched for case–control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, ten studies, comprising 2,696 lung cancer cases and 3,948 controls were included. Overall, for the G allele carriers (TG + GG) versus homozygote TT, the pooled OR was 1.037 (95% CI = 0.928–1.159 P = 0.001 for heterogeneity), for GG versus TT the pooled OR was 0.997 (95% CI = 0.861–1.154 P = 0.005 for heterogeneity). In the stratified analysis by ethnicity, significantly risks were not found among Asians or Caucasians. However, in the subgroup analyses by smoking status, significantly risks were found among smokers not in non-smokers. This meta-analysis suggested that the APE1 T1349G (Asp148Glu) polymorphism was not associated with lung cancer risk among Asians or Caucasians. But, the APE1 G allele was an increased risk factor for developing lung cancer among smokers.     

Multiple analytical approaches reveal distinct gene-environment interactions in smokers and non smokers in lung cancer

Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11–2.59,p = 0.01), whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25–0.65,p<0.001 and OR = 0.51;95%CI = 0.33–0.78,p = 0.002 respectively). In smokers, EPHX1 Tyr113His and SULT1A1 Arg213His polymorphisms reduced the risk of lung cancer, whereas CYP1A1*2A, CYP1A1*2C and GSTP1 Ile105Val imparted increased risk in non-smokers only. While exploring non-linear interactions through CART analysis, smokers carrying the combination of EPHX1 113TC (Tyr/His), SULT1A1 213GG (Arg/Arg) or AA (His/His) and GSTM1 null genotypes showed the highest risk for lung cancer (OR = 3.73;95%CI = 1.33–10.55,p = 0.006), whereas combined effect of CYP1A1*2A 6235CC or TC, SULT1A1 213GG (Arg/Arg) and betel quid chewing showed maximum risk in non-smokers (OR = 2.93;95%CI = 1.15–7.51,p = 0.01). MDR analysis identified two distinct predictor models for the risk of lung cancer in smokers (tobacco chewing, EPHX1 Tyr113His, and SULT1A1 Arg213His) and non-smokers (CYP1A1*2A, GSTP1 Ile105Val and SULT1A1 Arg213His) with testing balance accuracy (TBA) of 0.6436 and 0.6677 respectively. Interaction entropy interpretations of MDR results showed non-additive interactions of tobacco chewing with SULT1A1 Arg213His and EPHX1 Tyr113His in smokers and SULT1A1 Arg213His with GSTP1 Ile105Val and CYP1A1*2C in nonsmokers. These results identified distinct gene-gene and gene environment interactions in smokers and non-smokers, which confirms the importance of multifactorial interaction in risk assessment of lung cancer.     

Combined analysis of the association between p73 G4C14-to-A4T14 polymorphisms and cancer risk

P73 is a structural and functional homologue of p53, and plays an important role in regulating cell cycle and apoptosis. A potentially functional polymorphism (designated as p73 G4C14-to-A4T14) has been identified in a region in exon 2 of the p73 gene, which may theoretically form a stem-loop structure and thereby affect p73 expression. Several investigations have reported the correlation between p73 G4C14-to-A4T14 polymorphism and cancer risk. However, the results are inconclusive. To further assess the association between p73 polymorphism and cancer risk, we performed meta-analysis of the data sets obtained from 26 individual studies involving 8,148 cancer patients and 8,150 controls. The association between p73 G4C14-to-A4T14 polymorphism and cancer risk was determined by crude odd ratios (OR) with 95% CI (confidential interval). AT-allele carriers were found to have a significantly increased risk of cervical cancer (AT/GC vs. GC/GC, OR = 1.63, 95% CI = 1.14–2.33; AT/AT + AT/GC vs. GC/GC, OR = 1.49, 95% CI = 1.05–2.10), colorectal cancer (AT/AT vs. AT/GC + GC/GC, OR = 1.98, 95% CI = 1.25–3.12), head and neck cancer (AT/AT + AT/GC vs. GC/GC, OR = 1.44, 95% CI = 1.06–1.96) and other cancers (AT/AT vs. GC/GC, OR = 1.78, 95% CI = 1.24–2.57; AT/AT vs. AT/GC + GC/GC, OR = 1.80, 95% CI = 1.26–2.56). In the stratified analysis of ethnicity, a significantly elevated cancer risk was found in Caucasians (AT/AT + AT/GC vs. GC/GC, OR = 1.18, 95% CI = 1.08–1.30; allele AT vs. allele GC, OR = 1.15, 95% CI = 1.06–1.24). No significant association of p73 polymorphism with the cancer risk of smoking was detected by stratified analysis by smoking status. Together, our data suggest that the p73 G4C14-to-A4T14 may be a risk factor of cancer especially in Caucasians.     

The XRCC1 Arg280His polymorphism contributes to cancer susceptibility: an update by meta-analysis of 53 individual studies

The X-ray repair cross-complementing group 1 (XRCC1) protein plays a central role in DNA repair pathways. Epidemiological studies have revealed the association between XRCC1 Arg280His polymorphism and cancer risk, but the results were inconsistent. We conducted this meta-analysis to assess the effect of XRCC1 Arg280His polymorphism on cancer susceptibility with accumulated data. Up to January 2012, 53 case‐control studies with 21,349 cases and 23,649 controls were available for our study. Summary odds ratios (OR) and corresponding 95% confidence intervals (CIs) for XRCC1 Arg280His polymorphism and cancer were estimated using fixed‐ or random-effects models when appropriate. Our meta-analysis identified that elevated cancer risk was statistically associated with the minor variant His allele and Arg–His/His–His genotypes both in the overall population (allele comparison, His versus Arg: OR = 1.16; 95% CI: 1.08–1.25; dominant comparison, Arg–His/His–His versus Arg–Arg: OR = 1.17; 95% CI: 1.08–1.27) and in terms of subgroup analyses by ethnicity for both Caucasians and non‐Caucasians. However, no significant result was observed in the stratified analysis by cancer type. Moreover, significantly increased cancer risk was observed in smokers. These findings indicated that XRCC1 Arg280His polymorphism may play a role in cancer development.     

Polymorphisms of the CYP1A1 and CYP2E1 genes in head and neck squamous cell carcinoma risk

Polymorphisms in genes that encode P450 cytochrome enzymes may increase carcinogen activation or decrease their inactivation and consequently, promote the development of cancer. The aims of this study were to identify the MspI-CYP1A1, PstI-CYP2E1 and DraI-CYP2E1 polymorphisms in patients with head and neck cancer and to compare with individuals without cancer; to evaluate the association of these polymorphisms with risk factors and clinical histopathological parameters. In the study group, 313 patients were evaluated for CYP1A1, 217 for CYP2E1 (PstI) and 211 for CYP2E1 (DraI) and in the control group 417, 334 and 374 individuals, respectively. Molecular analysis was performed by PCR–RFLP technique, and chi-square and multiple logistic regression tests were used for statistical analysis. The result of analysis regarding individuals evaluated for CYP1A1 (MspI) showed that age (OR: 8.15; 95% CI 5.57–11.92) and smoking (OR: 5.37; 95% CI 3.52–8.21) were predictors for the disease; for the CYP2E1 (PstI and DraI), there were associations with age (PstI-OR: 9.10; 95% CI 5.86–14.14/DraI-OR: 8.07; 95% CI 5.12–12.72), smoking (PstI-OR: 4.10; 95% CI 2.44–6.89/DraI-OR: 5.73; 95% CI 3.34–9.82), alcohol (PstI-OR: 1.93; 95% CI 1.18–3.16/DraI-OR: 1.69; 95% CI 1.02–2.81), respectively, with disease development. CYP2E1 (PstI) was less frequent in patient group (OR: 0.48; 95% CI 0.23–0.98). Regarding clinical histopathological parameters, CYP1A1 polymorphism was less frequent in the larynx primary anatomic site (OR = 0.45; 95% CI = 0.28–0.73; P = 0.014). In conclusion, we confirm that age, smoking and alcohol consumption are risk factors for this disease and the polymorphisms investigated have no association with the development of head and neck cancer.     

An investigation of the relationship between SULT1A1 Arg213His polymorphism and lung cancer susceptibility in a Turkish population

Human sulfotransferase 1A1 (SULT1A1), the most expressed isoform of the phenol SULT1 subfamily, is an important member of sulfotransferase superfamily. A transition, G to A at position 638, in SULT1A1 gene, results in Arg²¹³His change. This single nucleotide polymorphism reduces the activity and thermostability of SULT1A1 enzyme. Thus, in the present study the relationship between SULT1A1 Arg²¹³His polymorphism and lung cancer was investigated. One hundred and six case and 271 control samples were studied using PCR‐RFLP. There was no significant difference in genotype and allele distribution between lung cancer and control populations (p = 0.07; p = 0.06, respectively). Compared with the SULT1A1*1/SULT1A1*1 genotype the variant SULT1A1 genotype (SULT1A1*1/SULT1A1*2 or SULT1A1*2/SULT1A1*2) was associated with a significantly increased lung cancer risk in cases (p = 0.027). In male populations, there was no significant difference between case and controls (p = 0.313). In female populations, however, this difference was found to be significant (p = 0.04). In smoker and non‐smoker populations, no significant relationship was evident between lung cancer and control population (p = 0.170, p = 0.065, respectively). Statistical analyses of histological types of lung cancer in comparison with the control individuals indicated a significant difference between SULT1A1 Arg²¹³His polymorphism and SCC (p = 0.027) and other types of cancer (p = 0.037), except SMCC (p = 0.854). Copyright © 2009 John Wiley & Sons, Ltd.     

<Emphasis Type="Italic">PARP-1 Val762Ala</Emphasis> polymorphism,CagA<Superscript>+</Superscript><Emphasis Type="Italic">H. pylori</Emphasis> infection and risk for gastric cancer in Han Chinese population

Introduction PARP-1 plays important role in the BER (base excision repair) and maintenance of genomic integrity. Previous study found the Val762Ala genetic variant in the PARP-1 gene contributed to susceptibility of some cancers and decreased PARP-1 enzyme activity in response to oxidative damage. Helicobacter pylori (H. pylori) infection was thought to be one of the major causes of gastric cancer. In this study, we investigated the association between the PARP-1 Val762Ala polymorphism, CagA⁺ H. pylori infection, and the risk for gastric cancer. Methods This hospital-based, case–control study was performed involving 556 individuals (236 cases with gastric cancer and 320 controls without evidence of neoplasm and gastrointestinal disease) using a PCR-RFLP method. Chi-square test and logistic regression analysis were used to count OR and 95% CI. Results 762Ala/Ala genotype was overrepresented in the cases (16.9%) compared with controls (10.3%), (OR, 1.942; 95% CI, 1.157–3.257, P = 0.011). Multivariate analysis showed that two factors were significantly associated with risk of gastric cancer, including CagA⁺ H. pylori infection (OR, 2.562; 95% CI, 1.174–5.240, P = 0.037), PARP-1 762AA genotype (OR, 1.772; 95% CI, 1.065–3.867; P = 0.042). Stratification analysis indicated that among Cag⁺ H. pylori positive subjects, 762Ala/Ala carriers had higher risk for developing gastric cancer compared with 762Val/Val carrier (OR, 2.337; 95% CI, 1.148–4.758; P = 0.017). Conclusion PARP-1 762Ala/Ala could be a risk factor for gastric cancer in Han Chinese population; PARP-1 762Val/Ala polymorphism and Cag⁺ H. pylori infection jointly contribute to higher risk for gastric cancer.     

Meta-analyses of the effect of cytochrome P450 2E1 gene polymorphism on the risk of head and neck cancer

Many studies have investigated the association between the CYP2E1 5′-flanking region (RsaI/PstI) polymorphism and head and neck cancer susceptibility, but the results were conflicting. In this meta-analysis, we assessed 24 published studies involving 12,562 subjects of the association between CYP2E1 RsaI/PstI polymorphism and head and neck cancer risk. Using the fixed effects model, we found significant association between PstI/RsaI polymorphism and head and neck cancer risk [OR = 1.11 (95%CI: 1.00–1.22) for c2 allele (P = 0.04) and OR = 1.57 (95% CI: 1.14–2.15) for c2 homozygous (P = 0.006) compared with wild type homozygote]. Significant results were also found in East Asians and Mix populations when stratified by ethnicity. However, no significant associations were found for Caucasians in all genetic models. Stratified analyses according to source of controls, significant associations were found only in hospital base controls. In the subgroup analyses by tumor types, significant association was detected only in oral cancer group, while no significant associations among laryngeal- or pharyngeal- cancer subgroup. This meta-analysis suggests that the CYP2E1 RsaI/PstI polymorphism may be a risk factor for head and neck cancer in Asians and Mix population, and that different carcinogenic processes involved in the genesis of various tumor types may exist.     

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.     

Association between <Emphasis Type="Italic">GSTM1</Emphasis>, <Emphasis Type="Italic">GSTT1</Emphasis>, and <Emphasis Type="Italic">GSTP1</Emphasis> polymorphisms and lung cancer risk in a Turkish population

Several studies focused on investigating genetic polymorphisms in order to estimate genetic contribution to lung cancer often showed conflicting results. In this study, we investigated the role of GSTM1, GSTT1, GSTP1 exon 5 and exon 6 polymorphisms on developing lung cancer and histological subtypes in 213 lung cancer patients and 231 controls. GSTM1 null, GSTT1 null, and GSTP1 exon 5 variant genotypes did not show a significant risk for developing lung cancer overall. Significant association was noted between GSTP1 exon 6 variant genotypes and overall lung cancer risk (OR 2.17, 95% CI 1.25–3.78; P = 0.006). These results show that GSTP1 exon 6 polymorphism might be an important factor in determining lung cancer susceptibility in a Turkish population.     

Survivin promoter ?31G/C (rs9904341) polymorphism and cancer susceptibility: a meta-analysis

This study aimed to perform a meta-analysis to assess the association of survivin −31 G/C promoter polymorphism and cancer risk. Thirteen case–control studies identified through PubMed and published between 2007 and 2011 with a total of 3329 cancer cases and 3979 controls were included in this meta-analysis. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association. Overall, the pooled analysis showed that survivin −31C allele was associated with 1.27 fold increased risk of cancer compared with the −31G allele (95% CI = 1.091–1.479; random model). Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that survivin −31G/C polymorphism was not associated with risk of gastric cancer [OR = 2.879; 95% CI = 0.553–15.004) for CC vs.GG] and esophageal cancer [OR = 1.352; 95% CI = 0.494–3.699) for CC vs.GG]. Stratification on the basis of ethnicity showed that the risk due to −31C allele was significant only in Asian population [OR = 1.894; 95% CI = 1.206–2.974 for CC vs.GG]. The present meta-analysis suggests an important role of survivin −31 G/C polymorphism with cancer risk especially in Asian population. However, further studies with larger sample size are required to draw more comprehensive conclusions and provide more precise evidence in individual cancers.