Interactions between Glutathione-S-Transferase M1, T1 and P1 polymorphisms and smoking,and increased susceptibility to esophageal squamous cell carcinoma

Background: A complex of genetic and environmental factors is involved in carcinogenesis of the esophageal squamous cell carcinoma (ESCC). Glutathione-S-Transferases (GSTs) are phase-II enzymes playing role in detoxification of carcinogen electrophiles. Genetic polymorphisms of GSTM1, GSTT1 and GSTP1 in association with some environmental factors and their impact on esophageal cancer susceptibility were assessed in the Iranian population. Methods: Genomic DNA of peripheral blood leukocytes from 148 confirmed esophageal cancer cases and 137 healthy individuals as control group was assayed for restriction fragment length polymorphisms in the GSTP1 loci by PCR amplification followed by digestion with Alw26I. Deletion of the GSTM1 and GSTT1 genes was detected by multiplex PCR. A data-mining method based on decision trees was applied to produce a predictive model of interactions between genotypes. Results: Smoking was independently associated with ESCC (p < 0.05, OR: 2.286, 95% CI = 1.311–3.983). Smoking along with GSTP1 Val/Val genotype was associated to ESCC (p < 0.001, OR: 3.886, 95% CI = 1.830–8.251), while non-smokers with GSTP1 Val/Val were significantly more frequent in non-cancerous group. (p = 0.007, OR: 0.507, 95% CI = 0.309–0.830). Conclusions: Data-mining methods are useful tools to map out a scheme for predicting complex relations and combinations of different genotypes. Genotyping analysis of GSTP1 together with assessment of smoking seems to be important in determining the risk of ESCC in the Iranian population.     

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.     

Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer

Methylating agents are involved in carcinogenesis, and the DNA repair protein O⁶-methylguanine-DNA methyltransferase (MGMT) removes methyl group from O⁶-methylguanine. Genetic variation in DNA repair genes has been shown to contribute to susceptibility to squamous cell carcinoma of the head and neck (SCCHN). We hypothesize that MGMT polymorphisms are associated with risk of SCCHN. In a hospital-based case–control study of 721 patients with SCCHN and 1234 cancer-free controls frequency-matched by age, sex and ethnicity, we genotyped four MGMT polymorphisms, two in exon 3, 16195C > T and 16286C > T and two in the promoter region, 45996G > T and 46346C > A. We found that none of these polymorphisms alone had a significant effect on risk of SCCHN. However, when these four polymorphisms were evaluated together by the number of putative risk genotypes (i.e. 16195CC, 16286CC, 45996GT + TT, and 46346CA + AA), a statistically significantly increased risk of SCCHN was associated with the combined genotypes with three to four risk genotypes, compared with those with zero to two risk genotypes (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) = 1.05–1.53). This increased risk was also more pronounced among young subjects (OR = 1.81; 95% CI = 1.11–2.96), men (OR = 1.24; 95% CI = 1.00–1.55), ever smokers (OR = 1.25; 95% = 1.01–1.56), ever drinkers (OR = 1.29; 95% CI = 1.04–1.60), patients with oropharyngeal cancer (OR = 1.45; 95% CI = 1.12–1.87), and oropharyngeal cancer with regional lymph node metastasis (OR = 1.52; 95% CI = 1.16–1.89). In conclusion, our results suggest that any one of MGMT variants may not have a substantial effect on SCCHN risk, but a joint effect of several MGMT variants may contribute to risk and progression of SCCHN, particularly for oropharyngeal cancer, in non-Hispanic whites.     

Risk of hospitalization among survivors of childhood and adolescent acute lymphoblastic leukemia compared to siblings and a general population sample

BackgroundAcute Lymphoblastic Leukemia (ALL) has a high survival rate, but cancer-related late effects in the early post-treatment years need documentation. Hospitalizations are an indicator of the burden of late effects. We identify rates and risk factors for hospitalization from five to ten years after diagnosis for childhood and adolescent ALL survivors compared to siblings and a matched population sample.Methods176 ALL survivors were diagnosed at ≤22 years between 1998 and 2008 and treated at an Intermountain Healthcare facility. The Utah Population Database identified siblings, an age- and sex-matched sample of the Utah population, and statewide inpatient hospital discharges. Sex- and birth year-adjusted Poisson models with Generalized Estimating Equations and robust standard errors calculated rates and rate ratios. Cox proportional hazards models identified demographic and clinical risk factors for hospitalizations among survivors.ResultsHospitalization rates for survivors (Rate:3.76, 95% CI = 2.22–6.36) were higher than siblings (Rate:2.69, 95% CI = 1.01–7.18) and the population sample (Rate:1.87, 95% CI = 1.13–3.09). Compared to siblings and population comparisons, rate ratios (RR) were significantly higher for survivors diagnosed between age 6 and 22 years (RR:2.87, 95% CI = 1.03–7.97 vs siblings; RR:2.66, 95% CI = 1.17–6.04 vs population comparisons). Rate ratios for diagnosis between 2004 and 2008 were significantly higher compared to the population sample (RR:4.29, 95% CI = 1.49, 12.32), but not siblings (RR:2.73, 95% CI = 0.54, 13.68). Survivors originally diagnosed with high-risk ALL did not have a significantly higher risk than siblings or population comparators. However, high-risk ALL survivors (Hazard ratio [HR]:3.36, 95% CI = 1.33–8.45) and survivors diagnosed from 2004 to 2008 (HR:9.48, 95% CI = 1.93–46.59) had the highest risk compared to their survivor counterparts.ConclusionsFive to ten years after diagnosis is a sensitive time period for hospitalizations in the ALL population. Survivors of childhood ALL require better long-term surveillance.     

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.     

The functional −94 insertion/deletion ATTG polymorphism in the promoter region of NFKB1 gene increases the risk of sporadic colorectal cancer

Objective: To investigate the allele and genotype frequencies of NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism and to evaluate the association between the polymorphism and colorectal cancer (CRC) risk in Malaysian population. Methods: Genomic DNA was extracted from the peripheral blood samples of 474 study subjects, which consisted of 237 histopathologically confirmed CRC patients and an equal number of cancer-free controls. The NFKB1 ?94 ins/del ATTG (rs28720239) polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed by DNA sequencing. The association between the polymorphic genotypes and CRC risk was evaluated by deriving odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. Results: The frequencies of wildtype (del/del), heterozygous (del/ins) and variant (ins/ins) genotypes in CRC patients were 31.7%, 53.6% and 14.8%, respectively, while those in cancer-free controls were 35.0%, 58.2% and 6.8%, respectively. The frequency of the variant genotype was significantly higher in cases compared to controls (P < 0.01). Evaluation of the risk association of the polymorphic genotypes revealed that the variant genotype could contribute to a significantly increased risk of CRC (OR = 2.42, 95% CI = 1.24–4.73, P < 0.01). Conclusions: The variant allele of NFKB1 ?94 ins/del ATTG (rs28362491) polymorphism is associated with higher risk of sporadic CRC in Malaysian population.     

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.     

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 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.     

Seroprevalence and risk factors associated with Toxoplasma gondii in domestic pigs from Spain

Serum samples from 2970 (1400 sows, 1570 fattening) pigs, from 100 farms in the 10 main swine production regions in Spain were tested for antibodies against T. gondii by the modified agglutination test (MAT). Antibodies to T. gondii (MAT 1:25 or higher) were detected in 492 pigs (16.6%, 9.7% in fattening pigs and 24.2% in sows). The herd prevalence was 85.0% (95% CI: 78–92) and within-farm prevalence ranged from 2.9% to 92.8% (median = 17.6%). Statistically significant differences were observed among sampling regions with seroprevalence significantly higher in pigs from Valencia Community (27.3%), Extremadura (23.3%) and Catalonia (21.2%). A generalized estimating equations model indicated that the risk factors associated with T. gondii seroprevalence were: age, sows compared to fattening pigs (OR = 2.9; 95% CI = 1.83–4.53), lack of rodent control (OR = 1.9; 95% CI = 1.04–3.60) and presence of cats (OR = 1.6; 95% CI = 1.12–2.34). The seroprevalence observed in the present study indicates a widespread, although variable, exposure to T. gondii among domestic pigs in Spain, which might have important implications for public health. Management measures including control of rodents and cats on the farms could help to reduce the observed prevalence levels in Spain.     

A study on the association of TNF-α-308, IL-6-174, IL-10-1082 and IL-1RaVNTR gene polymorphisms with rheumatic heart disease in Pakistani patients

Inflammation is an important contributor to the pathogenesis of rheumatic heart disease (RHD), a disorder of heart valves caused by a combination of immune, genetic and environmental factors. Cytokines are important mediators of inflammatory and immune responses. The aim of this study was to investigate the role of cytokine gene polymorphisms and their potential usefulness as biomarkers in RHD patients from Pakistan. We screened 150 RHD patients and 204 ethnically matched controls for tumor necrosis factor (TNF)-α^-308G/A, interleukin (IL)-10^?1082 G/A, interleukin (IL)-6^-174 G/C and a variable number of tandem repeats (VNTRs) polymorphism of the IL-1Ra gene using polymerase chain reaction. The results showed that TNF-α^-308 A and IL-6^-174 G alleles were associated with susceptibility to RHD (p = 0.000; OR = 2.81; CI = 1.5–5.14 and p = 0.025; OR = 1.50; CI = 1.04–2.16 respectively). The TNF-α^-308 AA and GA genotypes were associated with susceptibility to RHD (p = 0.012; OR = 9.94; CI; 1.21–217.3 and p = 0.046; OR = 1.97; CI = 0.98–3.97 respectively) while the GG genotype seemed to confer resistance (p = 0.003; OR = 0.39; CI = 0.20–0.76). The GG genotype for IL-6^-174 was significantly associated with predisposition to RHD (p = 0.015; OR = 2.6; CI = 1.17–5.85). The A1 (four repeats) and A2 (two repeats) alleles at the IL-1Ra VNTR polymorphism were associated with resistance and susceptibility to RHD respectively. However, this polymorphism deviated from Hardy–Weinberg equilibrium in both patients and controls in our population. TNF-α^-308 and IL-6^-174 polymorphisms may be useful markers for the identification of individuals susceptible to RHD in Pakistan. These individuals could be provided aggressive prophylactic intervention to prevent the morbidity and mortality associated with RHD.     

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.     

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.     

Anthropometric features and cutaneous melanoma risk: A prospective cohort study in French women

BackgroundEpidemiological studies on anthropometric features and cutaneous melanoma risk in women yielded inconsistent results, with few analyses involving prospective cohort data. Our objective was to explore several anthropometric characteristics in relation to the risk of melanoma in women.MethodsWe prospectively analysed data from E3N, a French cohort involving 98,995 women born in 1925–1950. Participants completed self-administered questionnaires sent biennially over 1990–2008. Relative risks (RRs) and 95% confidence intervals (CIs) were computed using Cox proportional hazards regression models, adjusted for age, number of naevi, freckling, skin and hair colour, skin sensitivity to sun exposure, residential sun exposure, and physical activity.ResultsHeight was positively associated with melanoma in age-adjusted models only (RR = 1.27, 95% CI = 1.05–1.55 for ≥164 cm vs. <160 cm; P for trend = 0.02). After full adjustment, there was a significantly positive relationship between sitting-to-standing height ratio and melanoma risk (RR = 1.40, 95% CI = 1.06–1.86 for ≥0.533 vs. <0.518; P for trend = 0.02). A large body shape at menarche was inversely associated with the risk of melanoma (RR = 0.78, 95% CI = 0.62–0.98; compared with lean). However, weight, body mass index, body surface area, waist or hip circumference, sitting height or leg length were not significantly associated with risk.ConclusionThese results suggest that height, sitting-to-standing height ratio and body shape at menarche may be associated with melanoma risk. Further research is required to confirm these relationships and better understand the underlying mechanisms.     

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.     

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.     

Genetic polymorphisms involved in the inflammatory response and lung cancer risk: A case-control study in Japan

Evidence is accumulating that chronic inflammation may have an important mechanism for the development and progression of lung cancer. Therefore, genetic polymorphisms in genes that involved in the inflammatory response may be associated with lung cancer risk. We evaluated the role of tumor necrosis factor α (TNFA) rs1799724, interleukin 1β (IL1B) rs16944, IL6 rs1800796, myeloperoxidase (MPO) rs2333227 and C-reactive protein (CRP) rs2794520 in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). CRP rs2794520 (OR = 1.64, 95% CI = 1.19–2.26) and IL6 rs1800796 (OR = 1.41, 95% CI = 1.02–1.96) were associated with lung cancer risk. In addition, we assessed interactions between the polymorphisms and smoking. The polymorphisms did not significantly modify the association between smoking and lung cancer. As TNFA triggers a cytokine cascade, the modifying effect of the TNFA rs1799724 genotypes on the association of any of the remaining polymorphisms with lung cancer risk was also examined. There was a significant interaction between TNFA rs1799724 and MPO rs2333227 (P_interaction = 0.058). Future studies involving larger control and case populations will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the inflammation pathway in lung cancer.     

Association between periodontitis and common variants in the promoter of the interleukin-6 gene

We recently reported an association between interleukin-6 (IL6) polymorphisms (SNPs) and haplotypes and aggressive periodontitis (AgP). The aim of this study was to investigate this association in a larger cohort of subjects, affected by either aggressive or chronic periodontitis. Five IL6 SNPs were analyzed in 765 subjects (167 generalized aggressive periodontitis, 57 localized aggressive, 310 chronic periodontitis and 231 periodontally healthy). Among Caucasians (n = 454) there were moderate associations for ?1363T allele (p = 0.011) and for ?174GG and ?1363GG genotypes with diagnosis of periodontitis (respectively, p = 0.044, OR = 1.6, 95% CI = 1.0–2.4, and p = 0.017, OR = 1.8, 95% CI = 1.1–2.8, adjusted for age, gender and smoking). Haplotypes containing the ?174G>C, ?1363G>T and ?1480C>G polymorphisms were associated with diagnosis of periodontitis (p = 0.02). Subgroup analysis by disease phenotype showed associations for the localized AgP (LAgP) group and ?1480C>G and ?6106A>T SNPs (p = 0.007 and 0.010, respectively). Among Caucasians the genotypes IL6 ?1480 CC and ?6106 TT increased the adjusted OR for LAgP (OR = 3.09 and 2.27, respectively). This study supports the hypothesis that IL6 polymorphisms and haplotypes are moderately associated with periodontitis, possibly acting through influencing tissue levels of IL6. This association is stronger for LAgP than for other periodontal disease phenotypes.     

Disparities in the risk of the ER/PR/HER2 breast cancer subtypes among Asian Americans in California

BackgroundPopulation-based studies of breast cancer often aggregate all Asians into a single category termed Asian/Pacific Islander (API).Purpose(1) Describe the demographic and clinicopathologic features of early breast cancer utilizing all eight ER/PR/HER2 subtypes among white, black, Hispanic, American Indian, seven Asian ethnicities, and the aggregate API category; (2) ascertain the risk of the ER+/PR+/HER2+, ER−/PR−/HER2−, and ER−/PR−/HER2+ subtypes when compared with the ER+/PR+/HER2− subtype, among seven Asian ethnicities versus non-Hispanic white women and (3) contrast the results with the risk of these same subtypes when using the aggregate API category.MethodsUsing the California Cancer Registry, we identified 225,441 cases of stages 1–4 first primary female invasive breast cancer. Logistic regression was used to assess the association of race with the ER+/PR+/HER2+, ER−/PR−/HER2− (triple-negative), and the ER−/PR−/HER2+ subtypes versus the ER+/PR+/HER2− when adjusted for stage, age, tumor grade, and socioeconomic status. Models were fit separately for each subtype. Odds ratios for the seven Asian ethnicities and the aggregate API category using non-Hispanic white women as the reference category were computed.ResultsThere was an increased risk of the ER+/PR+/HER2+ subtype for the combined API category (OR = 1.16; 95% CI = 1.09–1.23). But only Southeast Asians (OR = 1.17; 95% CI = 1.04–1.31), Filipino (OR = 1.23; 95% CI = 1.12–1.36), and Korean (OR = 1.63; 95% CI = 1.38–1.99) women had an increased risk of this subtype. The reduced risk of the triple-negative subtype seen in APIs (OR = 0.84; 95% CI = 0.79–0.90) was only noted in Chinese (OR = 0.80; 95% CI = 0.70–0.91) and Filipino (OR = 0.65; 95% CI = 0.58–0.73) women whereas Indian Continent (OR = 1.25; 95% CI = 1.01–1.53) women had an increased risk of the triple-negative subtype.The race × stage interaction was statistically significant for the ER−/PR−/HER2+ subtype (p < 0.05). When stratified by stage, there was no statistically significant association of race with subtype in stages 3 and 4. APIs had an increased risk of the ER−/PR−/HER2+ subtype in stage 1 (OR = 1.59; 95% CI = 1.37–1.75) and stage 2 (OR = 1.42; 95% CI = 1.28–1.58) but this risk was not seen in Pacific Islander, Indian Continent, and Japanese women for either stage.ConclusionsAmong the Asian ethnicities, there is marked variability in the demographic and clinicopathologic features of breast cancer. Use of the ER/PR/HER2 subtypes reveals that the risk of the ER−/PR−/HER2−, ER+/PR+/HER2+, and ER−/PR−/HER2+ subtypes varies among the Asian population. The API category, is sometimes, but not always reflective of all Asian women.     

Increased serum 2-oxoglutarate associated with high myocardial energy expenditure and poor prognosis in chronic heart failure patients

Myocardial energy expenditure (MEE) and 2-oxoglutarate are elevated in chronic heart failure (CHF) patients compared with healthy controls. To explore whether 2-oxoglutarate could reflect the levels of MEE and predict the prognosis of CHF, 219 CHF patients and 66 healthy controls were enrolled. 2-Oxoglutarate was assayed with Liquid Chromatography–Mass Spectrometry/Mass Spectrometry (LC/MS/MS). CHF patients were divided into 4 groups according to interquartile range of MEE and followed for death or recurrent hospital admission due to CHF for the mean follow-up time 6.64 ± 0.16 months. 2-Oxoglutarate was increased in CHF patients compared with controls (P < 0.01) and correlated with estimated glomerular filtration rate (r = 0.142, P = 0.036), age (r = − 0.269, P < 0.01) and MEE levels (r = 0.307, P < 0.01) in a multiple linear correlation analysis in CHF patients. Furthermore, 2-oxoglutarate (OR = 3.470, 95% CI = 1.557 to 7.730, P = 0.002), N-terminal pro-B-type natriuretic peptide (OR = 4.013, 95% CI = 1.553 to 10.365, P = 0.004), age (OR = 1.611, 95% CI = 1.136 to 2.283, P = 0.007) and left ventricular ejection fraction (OR = 7.272, 95% CI = 3.110 to 17.000, P < 0.001) were independently associated with MEE on multiple logistic regression analysis. Kaplan–Meier event curves showed that high 2-oxoglutarate levels were associated with adverse outcomes (Log Rank, Chi² = 4.026, P = 0.045). This study showed that serum 2-oxoglutarate is associated with MEE levels, which can be used as potential biomarkers for MEE, and it can reflect the clinical severity and short-term outcome of CHF.