Glutathione S-transferase polymorphisms and survival in African-American and White colorectal cancer patients

Background: Glutathione S-transferase (GST) enzymes are involved in electrophile detoxification. The authors investigated the association between GST genotype and survival in a racially diverse, population-based cohort of colorectal cancer (CRC) patients followed for a median of 9.6 years. Methods: Interviews were conducted with 315 African-American and White CRC patients in Connecticut, 1987–1991. Tumor tissue (n = 197) was later retrieved from hospital of diagnosis and assayed using multiplex PCR (GSTM1 and GSTT1) and PCR and RFLP analysis (GSTP1). Cox proportional hazards models provided adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Individuals with Ile/Val or Val/Val GSTP1 genotypes had a decreased risk of death (multivariate adjusted HR = 0.72, 95% CI: 0.48, 1.09) relative to those with wild type (Ile/Ile). Among those who received chemotherapy, this benefit was more pronounced (HR = 0.35, 95% CI: 0.16, 0.79); the interaction of reduced function GSTP1 genotype and chemotherapy was significant (P = 0.05). GSTM1 and GSTT1 genotype were not associated with survival. GSTM1, GSTT1, and GSTP1 genotype did not vary by race and did not contribute significantly to the survival disadvantage observed in African-Americans. Conclusions: In summary, GSTP1 genotype may play a role in CRC survival in African-Americans and Whites, particularly among those who receive chemotherapy.     

Glutathione S-transferase M1, T1, and P1 polymorphisms and thyroid cancer risk: A meta-analysis

Glutathione S-transferases (GSTs) genetic variants have been explored extensively as a predictive factor for cancer etiology. This meta-analysis aimed to examine the associations GSTM1, GSTT1, and GSTP1 genetic polymorphisms with thyroid cancer risk. PubMed, EMBASE, Cochrane Library, and HuGNet database were searched up to November 2011 using the appropriate terms. Twelve studies regarding GSTM1 null polymorphism (1569 cases and 2907 controls), 11 studies concerning GSTT1 null polymorphism (1515 cases and 2863 controls), and 8 studies on GSTP1 Ile105Val (965 cases and 1604 controls) were included in the meta-analysis. The random effects odds ratio was 1.07 (95% CI: 0.88–1.31; I² = 54.1%, P for heterogeneity = 0.013) for the GSTM1 null vs. present genotype and 1.08 (95% CI: 0.75–1.57; I² = 81.4%, P for heterogeneity < 0.001) for the GSTT1 null vs. present genotype, and 1.02 (95% CI: 0.70–1.49; I² = 74.6%, P for heterogeneity < 0.001) for the GSTP1 Val/Val + Val/Ile vs. Ile/Ile genotype. Similarly, no significant associations were demonstrated for subgroup analyses performed by ethnicity and histological type. In conclusion, these three polymorphisms are unlikely to be major determinants of susceptibility to thyroid cancer. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation. The relationship between these three genes and thyroid carcinoma must be evaluated further with gene–gene and gene–environment interactions.     

Polymorphisms of glutathione-S-transferase M1 and T1 and prostate cancer risk in a Tunisian population

Several genes involved in the metabolism of carcinogenesis have been found to be polymorphic in the human population, and specific alleles are associated with increase risk of cancer of various sites. This study is focused on the polymorphic enzymes glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) that involved in the detoxification of many xenobiotics involved in the etiology of prostate cancer. Objective. To evaluate whether GSTM1 and/or GSTT1 contribute to prostate cancer (CaP) etiology, we studied 110 incident CaP cases and 122 controls. Results. The probability of having CaP was increased in men who had homozygous deleted (non-functional) genotypes at GSTT1 (OR = 2.17; 95% CI = 1–3.79) but not GSTM1 (OR = 0.89; 95% CI = 0.66–1.88). Hence, individuals lacking the GSTT1 gene are at approximately twofold higher risk of developing prostate cancer in comparison with individuals with at least one active allele in the GSTT1 locus. Conclusion. These results suggest that GSTT1 is associated with CaP risk. The effect of smoking associated with the GSTT10/0 genotype was not found to affect the risk of prostate cancer.     

Genetic polymorphism of glutathione S-transferase T1 and the risk of colorectal cancer: A meta-analysis

Background: Studies investigating the association between genetic polymorphism of glutathione S-transferase T1 (GSTT1) and risk of colorectal cancer have reported conflicting results. In order to clarify the effect of GSTT1 polymorphism on the risk of developing colorectal cancer, we carried out a meta-analysis using published data to obtain more precise estimates of risk. Methods: Electronic searches of PubMed and EMBASE were conducted to select studies for this meta-analysis. Papers were included if they were observational studies investigating the association between GSTT1 polymorphism and colorectal cancer risk. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of colorectal cancer associated with GSTT1 null genotype. Results: We identified 30 eligible studies, which included 7635 cases and 12,911 controls. The combined results based on all studies showed that there was a statistically significant link between GSTT1 null genotype and colorectal cancer risk (OR = 1.20, 95% CI = 1.03–1.40). In the analysis of ethnic groups, we observed distinct differences associated with GSTT1 null genotype, the pooled odds ratios for the GSTT1 polymorphism were 1.32 in Caucasians (95% CI = 1.09–1.58) and 1.03 in Asians (95% CI = 0.81–1.32). As far as concerned the interaction between GSTT1 genotype and colorectal cancer risk in relation to smoking history, there was no increase in risk for smokers or nonsmokers with the GSTT1 null genotype (smokers: OR = 1.13, 95% CI = 0.80–1.60, nonsmokers: OR = 0.99, 95% CI = 0.71–1.38). When stratifying by the location of colorectal cancer, we found that there was a statistically significant link in rectal cancer (OR = 1.50, 95% CI = 1.09–2.07), but not in colon cancer (OR = 1.33, 95% CI = 0.94–1.88). No associations could be detected between null GSTT1 polymorphism and age, sex, tumor stage and differentiation. Conclusion: Our current study demonstrates that GSTT1 null genotype is associated with an increased risk of colorectal cancer, specifically, among Caucasians.     

The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene

1,3-Butadiene (BD) has been classified as a human carcinogen, group I; however, the relationship between polymorphisms of glutathione S-transferases that metabolize BD and chromosomal damage is not clear. The present study used sister chromatid exchange (SCE) and cytokinesis-block micronucleus (CBMN) assays to detect chromosomal damage in peripheral lymphocytes of 44 BD-exposed workers and 39 non-exposed healthy controls. PCR and PCR-RFLP were employed to detect three known glutathione S-transferase polymorphisms GSTT1, GSTM1, and GSTP1 (Ile105Val). The data demonstrated that the micronucleus (CBMN) frequency in BD-exposed workers was significantly higher than that in controls (frequency ratio (FR) = 1.48, 95% CI: 1.14–1.91, P < 0.01), and the CBMN frequency was higher in workers exposed to higher cumulative BD levels (FR = 1.70, 95% CI: 1.28–2.27, P < 0.01). However, differences in SCE frequency were not observed (FR = 1.14, 95% CI: 0.81–1.61, P > 0.05). Among exposed workers, chromosomal damage was related to BD exposure levels (FR = 1.35, 95% CI: 1.02–1.80, P < 0.05); age, older workers exhibited higher MN frequencies than younger workers (FR = 1.45, 95% CI: 1.14–1.84, P < 0.05); and years of work, those with more years of work exhibited higher MN frequencies than those with fewer years (FR = 1.40, 95% CI: 1.10–1.77, P < 0.05). Multivariate Poisson regression analysis showed that those who carried GSTM1 (?) (FR = 1.48, 95% CI: 1.14–1.92) or GSTT1 (?) (FR = 1.42, 95% CI: 1.10–1.83) genotypes, and especially those who carried both (FR = 2.10, 95% CI: 1.43–3.09) exhibited significantly higher MN frequencies than those carrying GSTM1 (+), GSTT1 (+) genotypes or their combination. The GSTP1 Val genotype did not affect MN frequency (P > 0.05). Our results suggested that higher levels of BD exposure in the workplace resulted in increased chromosomal damage, and that polymorphisms in GSTT1 and GSTM1 genes might modulate the genotoxic effects of BD exposure. Furthermore, the GSTT1 and GSTM1 polymorphisms exhibited an additive effect. Finally, urinary DHBMA was found to provide a biomarker that correlated with airborne BD levels.     

CYP1AI, glutathione S-transferase gene polymorphisms and risk of Polycythemia vera

Background: Associations between polymorphisms for gene encoding enzymes involved in biotransformation of xenobiotics and susceptibility to several cancers have been shown in several studies. The aim of the present study was to evaluate the association of polymorphisms of cytochrome P450 (CYP1A1) and GST deletions with the incidence of Polycythemia vera (PV) among the Jordanian population. Methods: The study included 61 PV patients and 70 cancer-free healthy controls. CYP1A1 (m1, m2, m3, m4) and GST (T1, M1) genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. The risk of cancer associated with gene polymorphisms was estimated by calculations of odds ratio (ORs) and confidence intervals (95% CIs) using Mantel–Haenszel statistics. Results: A statistically significant difference between the PV group and the control group was observed in the case of GSTM1 null genotype with 3.38 fold increase in risk of developing PV (95% CI = 1.63–7.01, p = 0.001) while GSTT1 null genotype showed no significance (OR = 1.11; 95% CI = 0.50–2.44, p = 0.38). No significant association was found between the CYP1A1 mutant genotypes (m1, m2, m4) and PV. The m3 genotype was absent in both patients and controls. Interestingly, a substantial significant increase of PV risk for the combination of GSTM1 null genotype and CYP1A1 m1 (T6235C) genotype was observed (OR = 4.38; 95% CI = 1.15–16.73, p = .02). Furthermore, the present case–control study showed that the studied Jordanian population generally resembles Caucasian populations with respect to the frequencies of CYP1A1 polymorphisms. Conclusion: Our data suggests that GSTM1 null genotype alone and in combination with CYP1A1 m1 genotype may be predisposing risk factors for PV in the Jordanian population.     

Genomic damages in peripheral blood lymphocytes and association with polymorphisms of three glutathione S-transferases in workers exposed to formaldehyde

DNA and chromosome damages in peripheral blood lymphocytes were evaluated in 151 workers occupationally exposed to formaldehyde (FA) and 112 non-FA exposed controls. The effects of polymorphisms in three glutathione-S-transferase (GSTs) genes on the DNA and chromosome damages were assessed as well. Alkaline comet assay and cytokinesis-block micronucleus (CBMN) assay were used to determine DNA and chromosome damages, respectively. The genotypes of GSTP1 (Ile105Val), GSTT1, and GSTM1 were assayed. The mean 8-h time-weighted average (TWA) concentrations of FA in two plywood factories were 0.83 ppm (range: 0.08–6.30 ppm). FA-exposed workers had higher olive tail moment (TM) and CBMN frequency compared with controls (Olive TM, 3.54, 95%CI = 3.19–3.93 vs. 0.93, 95%CI = 0.78–1.10, P < 0.01; CBMN frequency, 5.51 ± 3.37 vs. 2.67 ± 1.32, P < 0.01). Olive TM and the CBMN frequency also had a dose-dependent relation with the personal FA exposure. Significant association between FA exposure history and olive TM and CBMN frequency were also identified. The level of olive TM was slightly higher in FA-exposed workers with GSTM1 null genotype than those with non-null genotype (3.86, 95%CI = 3.31–4.50 vs. 3.27, 95%CI = 2.83–3.78, P = 0.07) with adjustment of covariates. We also found that FA-exposed workers carrying GSTP1 Val allele had a slightly higher CBMN frequency compared with workers carrying only the wild-type allele (6.32 ± 3.78 vs. 5.01 ± 2.98, P = 0.05). Our results suggest that the FA exposure in this occupational population increased DNA and chromosome damages and polymorphisms in GSTs genes may modulate the genotoxic effects of FA exposure.     

Novel functional variants locus in PLCE1 and susceptibility to esophageal squamous cell carcinoma: Based on published genome-wide association studies in a central Chinese population

A novel functional single nucleotide polymorphism (SNP) rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. In the present study, we validated this finding and also explored the risk of ESCC associated with other two unreported potentially functional SNPs (rs17417407 G > T and rs2274224 C > G) of PLCE1 in a population-based case–control study to investigate the association between these three potentially functional SNPs in PLCE1 and susceptibility to ESCC. A total of 381 ESCC cases and 420 controls matched by age and sex were recruited and successfully genotyped for three SNPs (rs17417407, rs2274223 and rs2274224) of the PLCE1 in a central Chinese population. SNP rs2274223 was independently associated with increased risk of ESCC (adjusted odds ratio [OR], 2.80; 95% confidence interval [95% CI], 1.45–5.39 for GG vs. AA), and SNP rs2274224 was found to be associated with decreased risk of ESCC (adjusted OR, 0.65; 95% CI, 0.46–0.91 for CG vs. CC). The combined effects of risk alleles for three SNPs (rs17417407T, rs2274223G and rs2274224G) were found to be associated with elevated risk of ESCC in a dose-dependent effect manner (P_trend = 0.005). The G_rs17417407A_rs2274223C_rs2274224 haplotype decreased the risk of ESCC (adjusted OR, 0.76; 95% CI, 0.62–0.93), meanwhile the G_rs17417407G_rs2274223C_rs2274224 and T_rs17417407G_rs2274223C_rs2274224 haplotypes could increase the risk of ESCC (adjusted OR, 1.75; 95% CI, 1.33–2.18 and OR, 2.51; 95% CI, 1.15–2.49). Gene–environment interaction analysis presented a best model consisted of four factors (rs2274223, rs2274224, family history, and smoking) with testing balance accuracy (TBA): 0.66 and cross validation consistency (CVC): 7/10, which could increase the esophageal cancer risk in the “high risk group” with 3.67-fold (OR: 3.67, 95% CI: 2.74–4.92), compared to the “low risk group”. Our results further confirmed that genetic variations in PLCE1 may contribute to ESCC risk associated with tobacco exposure in a central Chinese population. Further functional studies are needed to validate our results.     

Glutathione S-Transferase M1, T1, P1 Genotypes and Risk for Development of Colorectal Cancer

The glutathione S-transferase (GST) supergene family is an important part of cellular enzyme defense against endogenous and exogenous chemicals, many of which have carcinogenic potential. The present investigation was conducted to detect a possible association between polymorphisms at the GSTM1, GSTT1, and GSTP1 genes and the interaction with cigarette smoking and colorectal cancer incidence. We examined 181 patients with colorectal cancer and 204 controls. DNA was extracted from whole blood, and the GSTM1, GSTT1, and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler instrument. Associations between specific genotypes and the development of colorectal cancer were examined by use of logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 polymorphism was associated with an increased risk of developing colorectal cancer (OR = 1.62, 95% CI: 1.06–2.46). Also the risk of colorectal cancer associated with the GSTT1 null genotype was 1.64 (95% CI: 1.10–2.59). Statistically no differences were found between patients with colorectal cancer and control groups for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. In addition, the frequencies of the GSTM1 and GSTT1 deletion genotypes differed significantly between the cases and controls for current smokers; the GSTT1 null genotype especially is associated with a greater risk of colorectal cancer (OR = 2.44, 95% CI: 1.24–4.81). The GSTM1 and GSTT1 deletions were associated with an increased risk of developing a transverse or rectal tumor (OR = 1.86, 95% CI: 1.15–3.00; OR = 1.70, 95% CI: 1.02–2.84; respectively). The glutathione S-transferase polymorphisms were not associated with risk in patients stratified by age. The risk of colorectal cancer increased as putative high-risk genotypes increased for the combined genotypes of GSTM1 null, GSTT1 null, and either GSTP1 valine heterozygosity or GSTP1 valine homozygosity (OR = 2.69, 95% CI: 1.02–7.11). In conclusion, the results obtained in this study clearly suggest that those susceptibility factors related to different GST polymorphic enzymes are predisposing for colorectal cancer.     

Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population

Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160C<A) genes has been reported on Bangladeshi population relating those with colorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR = 2.58, 95% CI = 1.77–3.77, p < 0.05) and Pro/Pro mutant homozygosity (adjusted OR = 2.92, 95% CI = 1.78–4.78, p < 0.05) along with the combined genotype (Arg/Pro + Pro/Pro) (adjusted OR = 2.70, 95% CI = 1.90–3.82, p < 0.05) and colorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (p < 0.05) found to be associated with colorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR = 2.02, 95% CI = 1.42–2.87, p < 0.05). In conclusion, heterozygosity and mutant homozygosity as well as the combination of both TP53 Arg72Pro and CDH1 rs16260 polymorphisms are responsible to increase the risk of colorectal cancer development in Bangladeshi population.     

Genetic Polymorphisms of GSTM1, GSTT1, and GSTP1 with Prostate Cancer Risk: A Meta-Analysis of 57 Studies

Background and Objectives

The GSTM1, GSTT1 and GSTP1 polymorphisms might be involved in inactivation of procarcinogens that contribute to the genesis and progression of cancers. However, studies investigating the association between GSTM1, GSTT1 or GSTP1 polymorphisms and prostate cancer (PCa) risk report conflicting results, therefore, we conducted a meta-analysis to re-examine the controversy.

Methods

Published literature from PubMed, Embase, Google Scholar and China National Knowledge Infrastructure (CNKI) were searched (updated to June 2, 2012). According to our inclusion criteria, studies that observed the association between GSTM1, GSTT1 or GSTP1 polymorphisms and PCa risk were included. The principal outcome measure was the odds ratio (OR) with 95% confidence interval (CI) for the risk of PCa associated with GSTM1, GSTT1 and GSTP1 polymorphisms.

Results

Fifty-seven studies involving 11313 cases and 12934 controls were recruited. The overall OR, which was 1.2854 (95% CI = 1.1405–1.4487), revealed a significant risk of PCa and GSTM1 null genotype, and the similar results were observed when stratified by ethnicity and control source. Further, the more important is that the present study first reported the high risks of PCa for people who with dual null genotype of GSTM1 and GSTT1 (OR = 1.4353, 95% CI = 1.0345–1.9913), or who with GSTT1 null genotype and GSTP1 A131G polymorphism (OR = 1.7335, 95% CI = 1.1067–2.7152). But no association was determined between GSTT1 null genotype (OR = 1.102, 95% CI = 0.9596–1.2655) or GSTP1 A131G polymorphism (OR = 1.0845, 95% CI = 0.96–1.2251) and the PCa risk.

Conclusions

Our meta-analysis suggested that the people with GSTM1 null genotype, with dual null genotype of GSTM1 and GSTT1, or with GSTT1 null genotype and GSTP1 A131G polymorphism are associated with high risks of PCa, but no association was found between GSTT1 null genotype or GSTP1 A131G polymorphism and the risk of PCa. Further rigorous analytical studies are highly expected to confirm our conclusions and assess gene-environment interactions with PCa risk.     

Genetic polymorphisms in AURKA,BRCA1, CCNE1 and CDK2 are associated with ovarian cancer susceptibility among Chinese Han women

IntroductionCentrosome aberrations and cell-cycle deregulation have important implications for ovarian cancer development. The AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation.MethodsUsing a haplotype-based analysis, this study aimed to investigate whether genetic polymorphisms in these four genes may contribute to ovarian cancer susceptibility. A total of 22 single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 287 cases of ovarian serous cystadenocarcinomas and 618 age-matched cancer-free controls from the Chinese Han population, and then haplotype blocks were reconstructed according to our genotyping data and linkage disequilibrium (LD) status of these SNPs.ResultsFor AURKA, we found that haplotype GA [rs6064391 (T→G) + rs911162 (G→A)] was strongly associated with decreased ovarian cancer risk (adjusted OR = 0.31, 95% CI = 0.15–0.63, P = 0.0012). For BRCA1, we found that haplotype CGTAG was associated with decreased ovarian cancer risk (adjusted OR = 0.64, 95% CI = 0.41–0.98, P = 0.0417). Moreover, women harboring homozygous GA/CGTAG haplotypes showed the lowest risk (OR = 0.12, 95% CI = 0.02–0.94, P = 0.0438). In CCNE1, the SNPs rs3218035 and rs3218042 were significantly associated with increased ovarian cancer risk (rs3218035: adjusted OR = 5.20, 95% CI = 1.85–14.52, P = 0.0017; rs3218042: adjusted OR = 4.98, 95% CI = 1.75–14.19, P = 0.0027). For CDK2, no significant association was found.ConclusionsThis study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may affect ovarian cancer susceptibility in Chinese Han women.     

Association of genetic polymorphisms of glutathione-S-transferase genes (GSTT1, GSTM1, and GSTP1) and susceptibility to nonalcoholic fatty liver disease in Zahedan, Southeast Iran

Oxidative damage is thought to play a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Glutathione-S-transferases (GSTs) are involved in cell protection against oxidative stress. We examined whether GSTM1, GSTT1, and GSTP1 polymorphisms are associated with NAFLD in a sample of the Iranian population. The current case-control study included 83 patients with NAFLD and 93 healthy subjects. The GSTM1 and GSTT1 polymorphisms were analyzed by multiplex polymerase chain reaction (PCR). The GSTP1 polymorphism was detected by tetra amplification refractory mutation system-PCR assay. The GSTM1-null genotype was significantly associated with the development of NAFLD (odds ratios [OR]=2.171, 95% confidence intervals [CI]=1.188-3.970, p=0.015). The GSTP1 Val allele was shown to be a risk factor for NAFLD (OR=1.739, 95% CI=1.089-2.777, p=0.024). The GSTT1 polymorphism was not significantly different between control and patient groups (p=0.221). This study showed that GSTM1 and GSTP1, but not GSTT1, genetic polymorphisms are associated with NAFLD in a sample of the Iranian population, and may be used to determine the risk of development of NAFLD.     

Association between glutathione S-transferases M1, T1 and P1 gene polymorphisms and prostate cancer in Koreans

Prostate cancer (PCa) is the most commonly diagnosed cancer in the developed world, and the incidence of this cancer is rising rapidly in many countries. Several polymorphic genes encoding enzymes involved carcinogenesis have been studied as potential risk factor of prostate cancer. Genetic polymorphisms in glutathione S-transferases M1 (GSTM1), T1 (GSTT1) and P1 (GSTP1) genes have been constantly reported to have a meaningful effect on prostate cancer risk. But other surveys of this relationship have yielded inconsistent results. To assess the possible contribution of the GSTM1, GSTT1, and GSTP1 gene polymorphisms in prostate cancer, we performed a population-based study of 139 prostate cancer patients and 115 healthy controls based on their genotype distributions of the genes. There were no differences in distributions of genotype frequencies of GSTM1 and GSTP1 polymorphisms between prostate cancer patients and controls (OR 1.60, 95 % CI 0.886–2.860 for GSTM1 and OR 1.38, 95 % CI 0.739–2.577 for GSTP1). In contrast, the distribution of GSTT1-null genotype is significantly different between the prostate cancer case and controls (OR 0.26, 95 % CI 0.128–0.518, p < 0.001). Meanwhile, GSTP1 I/V and V/V genotypes were significantly associated with prostate cancer where the PSA level was more than 10.0 (OR 2.73, 95 % CI 1.319–5.639, p = 0.006). Thus, our data imply that the GSTT1-null genotype may not be a risk factor but a protective factor of prostate cancer and GSTP1 Val allele is a risk factor for the prostate cancer where the PSA level was high, although functional studies with larger sample size are necessary to elucidate these findings.     

Evening salivary cortisol and alpha-amylase at 14 months and neurodevelopment at 4 years: Sex differences

Stress system activity in early life can have long-term effects on neurodevelopment. The main aim of this study was to assess the association of child evening salivary cortisol and alpha-amylase basal levels at 14 months of age with longer-term neuropsychological development at 4 years in a low-risk population-based birth cohort derived from the INMA (Environment and Childhood) project in Spain. We included 186 parent-children pairs with information on both stress system activity and neurodevelopment. Both stress markers at 14 months of age showed an association with neuropsychological development at 4 years. Salivary cortisol showed a sex-specific pattern of association. In girls, cortisol levels at 14 months were negatively associated with cognitive development [long-term declarative memory (β = − 17.8, p = 0.028; 95% CI = − 33.2 to − 2.5); executive function (β = − 9.8, p = 0.08; 95% CI = − 21 to 1)] and gross motor development (β = − 13; p = 0.022; 95% CI = − 24 to − 2), whereas in boys cortisol levels were negatively associated with socioemotional development [autistic-like behaviours: Incidence Rate Ratio (IRR) = 1.6, p = 0.039; 95% CI = 1.01 to 2.41]. Salivary alpha-amylase was positively associated with socioemotional development in boys only [social competence (β = 2.11, p = 0.013; 95% CI = 0.47 to 3.72), autistic-like behaviours (IRR = 0.93, p = 0.042; 95% CI = 0.87 to 0.99) and hyperactivity symptoms (IRR = 0.81, p = 0.021; 95% CI = 0.69 to 0.97)]. These results suggest that stress system activity in early life is associated with longer-term neurodevelopment and that sex is an important factor in this relationship.     

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: A meta-analysis

Introduction: We conducted a systematic literature review and meta-analysis of oral cavity, esophageal, stomach, small intestine, colon, and rectal cancers among workers occupationally exposed to Cr(VI). Methods: Using PubMed, studies published from 1950 to 2009 evaluating the relationship between Cr(VI) exposure and GI cancers were identified. Measures of effect and variability were extracted from 32 studies meeting specific inclusion criteria, and meta-analysis summary relative risk measures were calculated using random effects models and inverse variance weighting methods. Results: Meta-standardized mortality ratios (SMRs) were, for cancer of the: oral cavity [1.02 (95% CI = 0.77–1.34)]; esophagus [1.17 (95% CI = 0.90–1.51)]; stomach [1.09 (95% CI = 0.93–1.28)]; colon [0.89 (95% CI = 0.70–1.12)]; and rectum [1.17 (95% CI = 0.98–1.39)]. Analyses of more highly exposed subgroups included in the studies or subgroups based on geographic region or by industry with recognized Cr(VI) exposures (welding, chrome plating, chromate production, and pigment production) did not result in elevated meta-SMRs except for esophageal cancer among US cohorts [meta-SMR = 1.49 (95% CI = 1.06–2.09)]. However, that finding was based on a subgroup of only four studies, one of which was a PMR study. Potential confounding by socioeconomic status (SES), diet and/or smoking, or limitations due to the healthy-worker effect (HWE) were evaluated, and while smoking, diet and SES may be important factors that may have upwardly biased the meta-SMRs, HWE is not likely to have significantly affected the summary results. None of three studies reporting small intestine cancers observed a statistically significant increased risk. Discussion: These meta-analyses and literature review indicate that Cr(VI)-exposed workers are not at a greater risk of GI cancers than the general population.     

Polymorphisms of tumor-related genes IL-10, PSCA,MTRR and NOC3L are associated with the risk of gastric cancer in the Chinese Han population

BackgroundGastric cancer is the fourth most common cancer in the world. Environmental and genetic factors both play critical roles in the etiology of gastric cancer. Hundreds of SNPs have been identified to have association with the risk of gastric cancer in many races. In this study, 25 SNPs in genes for IL-10, IL-1B, MTRR, TNF-а, PSCA, PLCE1 and NOC3L were analyzed to further evaluate their associations with gastric cancer susceptibility in the Chinese Han population.MethodsTwo hundred and seventy nine gastric cancer patients and 296 healthy controls were recruited in this study. SNP genotyping was conducted using Sequenom MassARRAY RS1000. Data management and statistical analyses were conducted by Sequenom Typer 4.0 Software and Pearson's χ² test.ResultsOne protective allele and three risk alleles for gastric cancer patients were found in this study. The allele “G” of rs1801394 in MTRR showed an association with a decreased risk of gastric cancer: odds ratio (OR) = 0.74, 95% confidence interval (95% CI) = 0.57–0.97, P = 0.030 in the additive model; OR = 0.495, 95% CI = 0.26–0.95, P = 0.034 in the recessive model. The other three SNPs, the allele “C” of rs1800871 in IL10 (OR = 1.33, 95% CI = 1.04–1.90; P = 0.026 in the additive model; OR = 1.46, 95% CI = 1.04–2.06; P = 0.030 in the recessive model), the allele “A” of rs2976391 in PSCA (OR = 1.30, 95% CI = 1.01–1.66; P = 0.041 in the additive model and OR = 1.48, 95% CI = 1.04–2.11, P = 0.028 in the recessive model), and the allele “G” of rs17109928 in NOC3L gene (OR = 1.34, 95% CI = 1.01–1.78; P = 0.042 by additive model analysis; OR = 1.47, 95% CI = 1.04–2.07, P = 0.028 by dominant model analysis), showed an association with an increased risk of gastric cancer.ConclusionsThese results indicate the importance of four gastric cancer susceptibility polymorphisms of IL-10, NOC3L, PSCA and MTRR in the Chinese Han population, which could be used in the determination of gastric cancer risk in clinical practice.     

Subtype analysis of Blastocystis sp. isolates from human and canine hosts in an urban community in the Philippines

Blastocystis sp. is a common gut-dwelling protist of both humans and animals. A cross-sectional survey among humans and their dogs was conducted to determine the prevalence of Blastocystis infection and to characterize the subtype (ST) distribution in an urban community in the Philippines. Fecal specimens from 1,271 humans and 145 dogs were collected and inoculated in diphasic culture medium. Prevalence of Blastocystis by culture was 13.0% (95% CI = 11.2–15.0) and 14.5% (95% CI = 9.6–21.2) for humans and dogs, respectively. A total of 168 culture isolates were genotyped using polymerase chain reaction (PCR) with seven pairs of ST-specific sequence-tagged-site (STS) primers. In humans, the ST present in this study were ST1 with 22.6% (95% CI = 17.2–29.0), ST2 with 3.1% (95% CI = 1.3–6.7), ST3 with 41.4% (95% CI = 34.9–48.6), ST4 with 14.8% (95% CI = 10.5–20.6), ST5 with 4.1% (95% CI = 2.0–8.0), and unknown ST with 13.9% (95% CI = 9.6–19.4). In dogs, the ST present in this study were ST1 with 4.3% (95% CI = 0.0–29.0), ST2 with 8.7% (95% CI = 1.3–28.0), ST3 with 17.4% (95% CI = 6.4–37.7), ST4 with 13.0% (95% CI = 3.7–33.0), ST5 with 13.0% (95% CI = 3.7–33.0), and unknown ST with 47.8% (95% CI = 29.2–67.0). This is the first study that reported Blastocystis ST4 in human and canine hosts in the Philippines.     

Prediction of all-cause mortality with copeptin in cardio-cerebrovascular patients: A meta-analysis of prospective studies

BackgroundMeasurement of the biomarker copeptin may help identify disease severity and risk of mortality for a various diseases. This study sought to determine the relationship between copeptin and all-cause mortality of patients with cardio-cerebrovascular disease.MethodsDatabase of Medline and Web of Science were searched for studies with data involving the baseline copeptin levels and subsequent all-cause mortality outcomes. The pooled HRs of all-cause mortality were calculated and presented with 95%CIs. Subgroup analysis and sensitivity analysis were conducted to explore the possible sources of heterogeneity.ResultsData from 14,395 participants were derived from 28 prospective studies. Higher copeptin significantly increased the risk of all-cause mortality (per unit copeptin: HR = 1.020, 95%CI = 1.004–1.036; log unit copeptin: HR = 2.884, 95%CI = 1.844–4.512; categorical copeptin: HR = 3.371, 95%CI = 2.077–5.472). Subgroup analysis indicated that the risk of all-cause death was higher in cerebrovascular patients (per unit copeptin: HR = 2.537, 95%CI = 0.956–6.731; log unit copeptin: HR = 3.419, 95%CI = 2.391–4.888) than cardiovascular patients (per unit copeptin: HR = 1.011, 95%CI = 1.002–1.020; log unit copeptin: HR = 2.009, 95%CI = 1.119–3.608).ConclusionCopeptin is associated with all-cause mortality of patients with cardiovascular and cerebrovascular disease. Our study suggests that copeptin seems to be a promising novel biomarker for prediction of mortality in cardio-cerebrovascular patients, especially for cerebrovascular patients.