XPF-673C>T Polymorphism Effect on the Susceptibility to Esophageal Cancer in Chinese Population

Purpose

Xeroderma pigmentsum group F (XPF) plays a pivotal role in DNA nucleotide excision repair and has been linked to the development of various cancers. This study aims to assess the association of XPF genetic variants with the susceptibility to esophageal squamous cell carcinoma (ESCC) in Chinese population.

Methods

This two-stage case-control study was conducted in a total of 1524 patients with ESCC and 1524 controls. Genotype of XPF -673C>T and 11985A>G variants were determined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Logistic regression analysis was performed to estimate odd ratios (ORs) and 95% confidence intervals (95% CI).

Results

Our case-control study showed that XPF -673TT genotype was associated with a decreased risk of ESCC compared with CC genotype in both case-control sets (Tangshan set: OR = 0.58; 95%CI = 0.34–0.99, P = 0.040; Beijing set: OR = 0.66; 95%CI = 0.46–0.95, P = 0.027). Stratified analyses revealed that a multiplicative interaction between -673C>T variant and age, sex or smoking status was evident (Gene-age: P_interaction = 0.002; Gene-sex: P_interaction = 0.002; Gene-smoking: P_interaction = 0.002). For XPF 11985A>G polymorphism, there was no significant difference of genotype distribution between ESCC cases and controls.

Conclusion

These findings indicated that genetic variants in XPF might contribute to the susceptibility to ESCC.     

Prenatal polymetallic exposure and small for gestational age: A case-control study in Taiyuan,China

BackgroundStudies focused on independent effects of metals on small for gestational age, failing to account for potential interdependence among metals.MethodsIn this case-control study, we selected 187 pregnant women and 187 matched controls from the First Hospital of Shanxi Medical University. Determination of 12 elements in the venous blood of pregnant women before delivery by ICP-MS. Logistic regression, weighted quantile sum regression (WQSR) and Bayesian kernel machine regression (BKMR) were used to estimate the overall effect and identify important mixture components that drive the associations with SGA.ResultsAn increased risk of SGA was associated with As (OR= 1.06,95%CI: 1.01,1.12), Cd (OR= 1.24,95%CI: 1.04,1.47) and Pb (OR= 1.05,95%CI: 1.02,1.08), while Zn (OR= 0.58,95%CI: 0.45,0.76) and Mn (OR= 0.97,95%CI: 0.94,0.99) were protective factors for SGA. In the WQSR positive model, the mixture of heavy metals has a positive combined effect on SGA (OR= 1.74,95%CI: 1.15, 2.62), with Sb and Cd having the highest weights. The BKMR models confirmed that the metal mixture was associated with decreased risk of SGA when the concentration of 12 metals was between the 30th percentile and the 65th percentile, and Zn and Cd had the greatest independent effect. Zn and SGA may not be linearly correlated, higher Zn level may reduce the effect of Cd on the risk of SGA.ConclusionsOur study suggested that exposure to multiple metals was associated with risk of SGA, and the observed association with multiple metals was dominated by Zn, Cd. Sb exposure during pregnancy may also increase the risk of SGA.     

Serum Homocysteine Concentration Is Significantly Associated with Inflammatory/Immune Factors

Recent studies suggest that serum homocysteine (HCY) level is correlated to inflammatory/immune factors that influence the development and progression of many diseases, such as cardiovascular disease. However, the association between serum HCY level and inflammatory/immune factors in healthy populations has not been systematically investigated. This study was conducted based on the Fangchenggang Area Male Health and Examination Survey (FAMHES) project. After comprehensive baseline analysis, we could not find any significant association between HCY level and inflammatory/immune factors. However, in the next linear regression analysis, serum C4 [age-adjusted: Beta = -0.053, 95%CI = (-3.798, -0.050), P = 0.044; multivariate adjusted: Beta = -0.064, 95%CI = (-4.271, -0.378), P = 0.019] and C-reactive protein (CRP) concentration [unadjusted: Beta = 0.056, 95%CI = (0.037, 0.740), P = 0.030] were positively related with HCY. In further binary regression analysis, a significant correlation was confirmed for C4 and HCY [age-adjusted: OR = 0.572, 95%CI = (0.359, 0.911); multivariate adjusted: OR = 0.558, 95%CI = (0.344, 0.905)]. In order to discover more potential associations, multivariate logistic regression analysis was applied and suggested that HCY and C4 were significantly correlated [age-adjusted: OR = 0.703, 95%CI = (0.519, 0.951); multivariate adjusted: OR = 0.696, 95%CI = (0.509, 0.951)]. In addition, immunoglobulin M (IgM) may influence the HCY level to some extent [unadjusted: OR = 1.427, 95%CI = (1.052, 1.936); age-adjusted: OR = 1.446, 95%CI = (1.061, 1.970); multivariate adjusted: OR = 1.447, 95%CI = (1.062, 1.973)]. Combining our results with recent studies, we propose that C4, CRP, and IgM in serum are significantly associated with HCY concentration. Further studies are needed on the mechanism of the interaction, especially among cardiovascular disease subjects.     

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.     

Association of p53 Arg72Pro polymorphism with bladder cancer: A meta-analysis

Background

p53 tumor suppressor gene Arg72Pro polymorphism has been associated with bladder cancer. However, results were inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and bladder cancer.

Methods

Electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association.

Results

The final meta-analysis included 14 published studies with 2176 bladder cancer cases and 2798 controls. The results suggested that the variant genotype was associated with the bladder cancer risk (additive model: OR = 1.72, 95% CI: 1.036–1.325, P = 0.011; dominant model: OR = 1.268, 95% CI: 1.003–1.602, P = 0.047) in Asian subgroup. However, the association was not significant between this polymorphism and bladder cancer risk in Caucasian (additive model: OR = 0.773, 95% CI: 0.564–1.059, P = 0.109; dominant model: OR = 0.685, 95% CI: 0.418–1.124, P = 0.134).

Conclusion

This meta-analysis suggests that p53 Arg72Pro polymorphism is associated with increased risk of bladder cancer in Asians. To validate the association between this polymorphism and bladder cancer, further studies with larger participants worldwide are needed.     

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.     

Genetic variation in members of the leukotrienes biosynthesis pathway confers risk of ischemic stroke in Eastern Han Chinese

This study was aimed to explore the association of genetic variation in members of the leukotrienes biosynthesis pathway as potential mediators with ischemic stroke (IS) risk in Eastern Han Chinese. A case-control study of was conducted with five selected single nucleotide polymorphisms (SNPs). In the single-locus analysis, carriers of C allele of rs730012 in LTC4S were more susceptible to IS (OR, 1.28; 95% CI, 1.02–1.60; P=0.033). Under the recessive genetic model, ALOX5 rs2029253 variant reduced IS risk (adjusted OR, 0.78; 95% CI, 0.60–1.00; P=0.048) while LTA4H rs6538697 and LTC4S rs730012 variants increased (adjusted OR, 1.66; 95% CI, 1.04–2.64; P=0.032 and adjusted OR, 3.63; 95% CI, 1.01–13.05; P=0.048, respectively). However, there was no evidence of association between all five SNPs and IS risk after correction for multiple testing. In combined analysis of multiple genes and loci, individuals with ALOX5AP rs12429692 T allele, ALOX5 rs2029253 A allele, and LTA4H rs6538697 C allele suggested a significantly increased susceptibility to IS (adjusted OR, 1.70; 95% CI, 1.07–2.69; P=0.024). The present study suggested gene–gene interactions in leukotrienes pathway could exert influences on the risk of IS.     

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.     

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.     

Functional polymorphisms in the IL6 gene promoter and the risk of urinary bladder cancer in India

BackgroundInterleukin-6 is a multifunctional cytokine, which plays a key role in tumor proliferation and differentiation. Variations in its gene (IL6) sequence may affect the risk of developing various cancers, including urinary bladder cancer. The present study was done to find the association of functional polymorphisms in the IL6 promoter with urinary bladder cancer.Materials and methodsSingle nucleotide polymorphisms were genotyped in histologically confirmed 232 cases of urinary bladder cancer and 250 healthy controls. The controls subjects were matched to the cases by age, sex, and ethnicity. Genotyping of the polymorphisms (−174G>C; −572G>C, −596A>G) was undertaken by direct DNA sequencing. The level of association between the genotypes and urinary bladder cancer risk was estimated by odds ratios and 95% confidence intervals generated by applying the chi-square test. Linkage disequilibrium (LD) between SNPs and haplotype analysis were performed using Haploview software.ResultSignificantly higher number of smokers (p = 0.047), tobacco chewers (p = <0.001) and those with non-vegetarian food habits (p = 0.016) were seen in the case group. The distribution of genotypes at −174G>C locus differed significantly between cases and controls and the variant genotypes GC + CC were significantly rarer in the cases (p = 0.00073; OR = 0.52 95% CI 0.35–0.75). Variant genotypes (GC + CC) were more common in grade I than grade III tumors (p = 0.032), further suggesting a protective effect. No LD was found between the SNPs; however, the frequency of haplotype AGC was significantly lesser in the cases than controls (p = 0.0103), suggesting a protective effect. Genotype distribution at the other two loci (−572G>C and −596A>G) did not show association with bladder cancer.ConclusionsIL6 (−174G>C) substitution confers significant protection against the risk of urinary bladder cancer in the study population, while other substitutions in this gene (−572G>C and −596A>G) do not affect the risk. In general, there is a lack of studies on the cytokine gene polymorphisms in urinary bladder cancer.     

Methylenetetrahydrofolate reductase gene polymorphisms contribute to acute myeloid leukemia and chronic myeloid leukemia susceptibilities: Evidence from meta-analyses

PurposeThe expression of methylenetetrahydrofolate reductase (MTHFR) is associated with acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Most studies have linked the common functional C677T and A1298C polymorphisms of the MTHFR gene and susceptibility to AML and CML, but the results were not consistent. The aim of the present study was to derive a more precise estimation of the relationship.MethodsMeta-analyses assessing the association of MTHFR C677T and A1298C variations with AML and CML were conducted. Eligible articles were identified from the PubMed and EMBASE databases. All statistical analyses were conducted using Review Manager Software.Results10 and 10 studies were included in the meta-analysis about the role of C677T polymorphism on the AML and CML risks, respectively; 6 and 4 studies were included about the role of A1298C polymorphism on the AML and CML risks, respectively. Overall, both the C677T and A1298C polymorphisms were significantly associated with CML risk under the recessive model (P = 0.04, OR = 1.35, 95% CI = 1.02–1.79 for C677T and P = 0.003, OR = 2.17, 95% CI = 1.29–3.63 for A1298C). In addition, the risk of CML was higher in 1298CC genotype carriers than in 1298AA genotype carriers (P = 0.004, OR = 2.17, 95% = 1.28–3.69). Conversely, the overall data failed to indicate a significant association of C677T or A1298C polymorphisms with AML risk under any model.ConclusionsThe findings provide evidence that C677T and A1298C polymorphisms are risk factors for CML risk.     

Prevalence of Suicide Attempts among College Students in China: A Meta-Analysis

BackgroundSuicide is the leading cause of death among 15–34 year olds in China, but no national data are available on the suicide and suicide attempts rates of college students, a sub-group of youth with 23 million. Several studies have reported the prevalence of suicide attempts among college students, however, no meta-analysis pooling the prevalence of suicide attempts is found.ResultsA total of 29 eligible studies, with 88,225 college students, were finally included. The maximum and minimum reported prevalences of suicide attempts among college students in China were 0.4% and 10.5%, respectively. The pooled prevalence of suicide attempts was 2.8% (95%CI: 2.3%–3.3%). Subgroup analyses showed that the pooled estimate of prevalence of life time suicide attempts was 2.7% (95%CI: 2.1%–3.3%), and 12-month suicide attempts was 2.9% (95%CI: 2.0%–3.8%). The prevalence for males was 2.4% (95%CI: 1.8%–3.0%), and for females was 2.7% (95%CI: 1.9%–3.7%). The prevalences among college students in grade 1 through 4 were 2.8% (95%CI: 1.7%–3.8%), 1.8% (95%CI: 1.2%–2.3%), 2.0% (95%CI: 0.8%–3.1%), and 2.9% (95%CI: 0.1%–6.7%), respectively. The prevalences among college students from rural and urban areas were 5.1% (95%CI: 2.8%–7.5%) and 3.7% (95%CI: 1.4%–5.9%), respectively.Conclusions2.8% prevalence of suicide attempts and more than 600,000 suicide attempters among college students indicate that suicide attempt among college students is an important public health problem in China. More attention should be paid to the current situation.     

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.     

Low Physical Activity and High Screen Time Can Increase the Risks of Mental Health Problems and Poor Sleep Quality among Chinese College Students

Objective

To test the independent and interactive associations of physical activity (PA) and screen time (ST) with self-reported mental health and sleep quality among Chinese college students.

Method

Data were collected in October, 2013. The gender, age, residential background, body mass index (BMI), perceived family economy and perceived study burden were obtained from a total of 4747 college students (41.6% males and 58.4% females). The outcomes were self-reported PA status, ST, anxiety, depression, psychopathological symptoms and sleep quality. Analyses were conducted with logistic regression models.

Results

Overall, 16.3%, 15.9% and 17.3% of the students had psychological problems, such as anxiety, depression and psychopathological symptoms, respectively. The prevalence of poor sleep quality was 9.8%. High ST was significantly positively associated with anxiety (OR=1.38, 95%CI: 1.15-1.65), depression (OR=1.76, 95%CI: 1.47-2.09), psychopathological symptoms (OR=1.69, 95%CI: 1.43-2.01) and poor sleep quality (OR=1.32, 95%CI: 1.06-1.65). High PA was insignificantly negatively associated with anxiety, depression, psychopathological symptoms and poor sleep. Low PA and high ST were independently and interactively associated with increased risks of mental health problems and poor sleep quality (p<0.05 for all).

Conclusion

Interventions are needed to reduce ST and increase PA in the lifestyles of young people. Future research should develop and measure the impacts of interventions and their potential consequences on sleep, health, and well being.     

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.     

A Meta-Analysis on the Relationship between Exposure to ELF-EMFs and the Risk of Female Breast Cancer

Objective

To comprehensively analyze the relationship between exposure to extremely low frequency electromagnetic fields (ELF-EMFs) and the development of female breast cancer.

Methods

Reports of case-control studies published from 1990 to 2010 were analyzed. The quality effect model was chosen to calculate total odds ratio (OR) depending on the data in studies and quality scores. Subgroup analyses were also performed by the situation of menopause, estrogenic receptor and exposure assessment respectively.

Results

For all 23 studies the OR was 1.07, 95% CI = 1.02–1.13, for estrogen receptor positive subgroup,OR = 1.11, 95% CI = 1.03–1.20; for premenopausal subgroup, OR = 1.11, 95% CI = 1.00–1.23. The results of other subgroups showed no significant association between ELF-EMF and female breast cancer.

Conclusion

ELF-EMFs might be related to an increased risk for female breast cancer, especially for premenopausal and ER+ females. However, it''s necessary to undertake better epidemiologic researches to verify the association between ELF-EMF and female breast cancer due to the limits of current study, especially the one on exposure assessment.     

Association of Ulcerative Colitis with FUT2 and FUT3 Polymorphisms in Patients from Southeast China

Objectives

Dysbiosis of intestinal microbiota has been implicated in ulcerative colitis (UC). Fucosyltransferase (FUT) 2 and FUT3 determine expression of histo-blood group antigens in the gut and may affect the intestinal microbiota. We investigated the association between FUT2 and FUT3 polymorphisms and UC in Chinese patients.

Methods

We genotyped FUT2 (rs281377, rs1047781 and rs601338) and FUT3 (rs28362459, rs3745635 and rs3894326) in 485 UC patients and 580 healthy controls using SNaPshot. We also evaluated expression of Lewis a and b antigens in the sigmoid colon of 7 UC patients and 7 patients with benign colonic polyps.

Results

The frequencies of mutant allele (A) and genotype (GA+AA) in FUT3 (rs3745635) were higher in UC patients than controls (P = 0.016, 95%CI: 1.339–1.699; P = 0.038, 95%CI: 1.330–1.742, respectively). Stratified analyses revealed that the frequencies of mutant allele (G) and genotype (TG+GG) of FUT3 (rs28362459) were significantly lower in patients with extensive colitis than those with distal colitis (P<0.001, 95%CI: 0.503–0.742; P = 0.001, 95%CI: 0.567–0.786, respectively). Similar conclusions were drawn for the mutant allele (A) and genotype (GA+AA) of FUT3 (rs3745635) in patients with extensive colitis compared to those with distal colitis (P = 0.006, 95%CI: 0.553–0.845; P = 0.011, 95%CI: 0.621–0.900, respectively). Although expression of Lewis b antigen in the sigmoid colon did not differ between UC patients and controls, Lewis a antigen expression was higher in the cryptic epithelium of both inflammatory and non-inflammatory sigmoid colon of UC patients than controls (P = 0.028).

Conclusions

Our findings indicated that polymorphisms in FUT3 and its intestinal expression might be associated with UC pathogenesis.     

Association of physical activity and polymorphisms in FGFR2 and DNA methylation related genes with breast cancer risk

PurposePhysical activity, a protective factor for breast cancer, increases the level of DNA methylation. Fibroblast growth factor receptor 2 (FGFR2), a confirmed breast cancer susceptibility gene, is predisposed to be methylated. Therefore, DNA methylation related genes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and DNA methyltransferase (DNMT), together with physical activity and FGFR2, may interact with each other to effect breast cancer risk.MethodsA total of 839 incident breast cancer cases and 863 age-matched controls from Guangzhou, China were included in this study. We used questionnaires to assess physical activity in metabolic equivalent (MET)-h/week/year and a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform to ascertain genotypes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated from logistic regression models.ResultsExercise activity and FGFR2 rs2981582 were confirmed to be associated with breast cancer risk, and were found to significantly interact (P for multiplicative and additive interactions = 0.045 and 0.021, respectively). Women who had CT/TT genotypes of FGFR2 rs2981582 and experienced exercise activity <3 MET-h/week/year had significantly increased risk (OR = 3.15, 95% CI = 2.28–4.35) compared to women with CC genotype and ≥3 MET-h/week/year. There was also a significant interaction between FGFR2 rs2981582 and MTHFR rs1801133 on breast cancer risk (P for multiplicative and additive interactions = 0.039 and 0.023, respectively).ConclusionWe found both a gene–environment (FGFR2-exercise activity) and a gene–gene (FGFR2–MTHFR) interaction on breast cancer risk. Our results suggest that environmental factors, such as physical activity, may be able to counteract genetic susceptibility to breast 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.     

Breast cancer risk and common single nucleotide polymorphisms in homologous recombination DNA repair pathway genes XRCC2, XRCC3, NBS1 and RAD51

The possible role for DNA repair deficiencies in cancer development, namely in breast cancer has been the subject of increasing interest since it has been reported that breast cancer patients might be deficient in the repair of DNA damage. Exposure to ionizing radiation has been pointed out as a risk factor for breast cancer, and the type of DNA lesions induced by this carcinogen can be repaired by homologous recombination DNA repair (HRR) pathway. To evaluate the potential modifying role of some single nucleotide polymorphisms (SNP) in HRR involved genes on the individual susceptibility to breast cancer we carried out a hospital based case–control study in a Caucasian Portuguese population (289 histological confirmed breast cancer patients and 548 control individuals). We genotyped 4 SNPs in 4 different HRR pathway genes, XRCC2 (Ex3 + 442G > A, R188H, rs3218536), XRCC3 (Ex8-5C > T, T241M, rs861539), NBS1 (Ex5-32C > G, E185Q, rs1805794) and RAD51 5′UTR (Ex1-59G > T, rs1801321), tagging 41 SNPs in these genes. The frequency of the different polymorphisms in the Portuguese control population is similar to the ones reported for other Caucasian populations, and the deviation of the Hardy–Weinberg equilibrium was only observed for the XRCC2 (Ex3 + 442G > A, R188H, rs3218536) polymorphism in the control population. The results obtained, after logistic regression analysis, did not reveal a major role of these polymorphisms on breast cancer susceptibility. However, when the population was stratified according to breast feeding (women that breast fed and women that never breast fed) it is observed, in women that never breast fed, that the heterozygous individuals for the XRCC2 (Ex3 + 442G > A, R188H, rs3218536) polymorphism have a decreased risk for breast cancer [adjusted OR = 0.45; 95% CI = 0.22–0.92] (P = 0.03). Additionally, after stratification according to menopausal status, our results suggest that post-menopausal women carrying at least one variant allele for the XRCC3 (Ex8-5C > T, T241M, rs861539) polymorphism have a lower risk for breast cancer [adjusted OR = 0.67; 95% CI, 0.47–0.94] (P = 0.03). Most of the studies suggest that breastfeeding may be responsible for 2/3 of the estimate reduction of breast cancer. The longer the duration of breastfeeding the lower the potential risk associated with breast cancer. Therefore, in our study the potential protective role of the variant allele of XRCC2 (Ex3 + 442G > A, R188H, rs3218536), in never breast fed women, might be related with a more efficient DNA repair activity.