T (null )and M (null )genotypes of the glutathione S-transferase gene are risk factor for CAD independent of smoking

BACKGROUND: The association of the deletion in GSTT1 and GSTM1 genes with coronary artery disease (CAD) among smokers is controversial. In addition, no such investigation has previously been conducted among Arabs. METHODS: We genotyped 1054 CAD patients and 762 controls for GSTT1 and GSTM1 deletion by multiplex polymerase chain reaction. Both CAD and controls were Saudi Arabs. RESULTS: In the control group (n = 762), 82.3% had the T (wild )M (wild)genotype, 9% had the T(wild )M (null), 2.4% had the T(null )M (wild )and 6.3% had the T(null )M (null )genotype. Among the CAD group (n = 1054), 29.5% had the T(wild )M (wild )genotype, 26.6% (p < .001) had the T(wild )M (null), 8.3% (p < .001) had the T(null )M (wild )and 35.6% (p < .001) had the T(null )M (null )genotype, indicating a significant association of the T(wild )M (null), T(null )M (wild )and T(null )M (null )genotypes with CAD. Univariate analysis also showed that smoking, age, hypercholesterolemia and hypertriglyceridemia, diabetes mellitus, family history of CAD, hypertension and obesity are all associated with CAD, whereas gender and myocardial infarction are not. Binary logistic regression for smoking and genotypes indicated that only M (null )and T(null)are interacting with smoking. However, further subgroup analysis stratifying the data by smoking status suggested that genotype-smoking interactions have no effect on the development of CAD. CONCLUSION: GSTT1 and GSTM1 null-genotypes are risk factor for CAD independent of genotype-smoking interaction

Motor ability in children treated for idiopathic clubfoot. A controlled pilot study

<p>Abstract</p> <p>Background</p> <p>To study motor ability at seven years of age in children treated for idiopathic clubfoot and its relation to clubfoot laterality, foot status and the amount of surgery performed.</p> <p>Methods</p> <p>Twenty children (mean age 7.5 years, SD 3.2 months) from a consecutive birth cohort from our hospital catchments area (300.000 inhabitants from southern Sweden) were assessed with the Movement Assessment Battery for Children (MABC) and the Clubfoot Assessment Protocol (CAP).</p> <p>Results</p> <p>Compared to typically developing children an increased prevalence of motor impairment was found regarding both the total score for MABC (p < 0.05) and the subtest ABC-Ball skills (p < 0.05). No relationship was found between the child's actual foot status, laterality or the extent of foot surgery with the motor ability as measured with MABC. Only the CAP item "one-leg stand" correlated significantly with the MABC (rs = -0.53, p = 0.02).</p> <p>Conclusions</p> <p>Children with idiopathic clubfoot appear to have an increased risk of motor activity limitations and it is possible that other factors, independent of the clinical status, might be involved. The ability to keep balance on one leg may be a sufficient tool for determining which children in the orthopedic setting should be more thoroughly evaluated regarding their neuromotor functioning.</p

Employment in the Ecuadorian cut-flower industry and the risk of spontaneous abortion

<p>Abstract</p> <p>Background</p> <p>Research on the potentially adverse effects of occupational pesticide exposure on risk of spontaneous abortion (SAB) is limited, particularly among female agricultural workers residing in developing countries.</p> <p>Methods</p> <p>Reproductive histories were obtained from 217 Ecuadorian mothers participating in a study focusing on occupational pesticide exposure and children's neurobehavioral development. Only women with 2+ pregnancies were included in this study (n = 153). Gravidity, parity and frequency of SAB were compared between women with and without a history of working in the cut-flower industry in the previous 6 years. Logistic regression analysis was conducted to assess the relation between SAB and employment in the flower industry adjusting for maternal age.</p> <p>Results</p> <p>In comparison to women not working in the flower industry, women working in the flower industry were significantly younger (27 versus 32 years) and of lower gravidity (3.3 versus 4.5) and reported more pregnancy losses. A 2.6 (95% CI: 1.03-6.7) fold increase in the odds of pregnancy loss among exposed women was observed after adjusting for age. Odds of reporting an SAB increased with duration of flower employment, increasing to 3.4 (95% CI: 1.3, 8.8) among women working 4 to 6 years in the flower industry compared to women who did not work in the flower industry.</p> <p>Conclusion</p> <p>This exploratory analysis suggests a potential adverse association between employment in the cut-flower industry and SAB. Study limitations include the absence of a temporal relation between exposure and SAB, no quantification of specific pesticides, and residual confounding such as physical stressors (i.e., standing). Considering that approximately half of the Ecuadorian flower laborers are women, our results emphasize the need for an evaluating the reproductive health effects of employment in the flower industry on reproductive health in this population.</p

Polymorphisms of XRCC1 genes and risk of nasopharyngeal carcinoma in the Cantonese population

BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China. In addition to environmental factors such as Epstein-Barr virus infection and diet, genetic susceptibility has been reported to play a key role in the development of this disease. The x-ray repair cross-complementing group 1 (XRCC1) gene is important in DNA base excision repair. We hypothesized that two common single nucleotide polymorphisms of XRCC1 (codons 194 Arg→Trp and 399 Arg→Gln) are related to the risk of NPC and interact with tobacco smoking. METHODS: We sought to determine whether these genetic variants of the XRCC1 gene were associated with the risk of NPC among the Cantonese population in a hospital-based case control study using polymerase chain reaction-restriction fragment length polymorphism analysis. We conducted this study in 462 NPC patients and 511 healthy controls. RESULTS: After adjustment for sex and age, we found a reduced risk of developing NPC in individuals with the Trp194Trp genotype (OR = 0.48; 95% CI, 0.27–0.86) and the Arg194Trp genotype (OR = 0.79; 95% CI, 0.60–1.05) compared with those with the Arg194Arg genotype. Compared with those with the Arg399Arg genotype, the risk for NPC was not significantly different in individuals with the Arg399Gln genotype (OR = 0.82; 95% CI, 0.62–1.08) and the Gln399Gln genotype (OR = 1.20; 95% CI, 0.69–2.06). Further analyses stratified by gender and smoking status revealed a significantly reduced risk of NPC among males (OR = 0.32; 95% CI, 0.14–0.70) and smokers (OR = 0.34; 95% CI, 0.14–0.82) carrying the XRCC1 194Trp/Trp genotype compared with those carrying the Arg/Arg genotype. No association was observed between Arg399Gln variant genotypes and the risk of NPC combined with smoking and gender. CONCLUSION: Our findings suggest that the XRCC1 Trp194Trp variant genotype is associated with a reduced risk of developing NPC in Cantonese population, particularly in males and smokers. Larger studies are needed to confirm our findings and unravel the underlying mechanisms

Cured meat, vegetables, and bean-curd foods in relation to childhood acute leukemia risk: A population based case-control study

<p>Abstract</p> <p>Background</p> <p>Consumption of cured/smoked meat and fish leads to the formation of carcinogenic <it>N-</it>nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia.</p> <p>Methods</p> <p>A population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age- and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses.</p> <p>Results</p> <p>Consumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15–2.64). Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37–0.83) and bean-curd (OR = 0.55; 95% CI: 0.34–0.89) was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea.</p> <p>Conclusion</p> <p>Dietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective.</p

Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals

Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis

Effect of HPV on head and neck cancer patient survival, by region and tumor site: A comparison of 1362 cases across three continents.

Abstract OBJECTIVES: To explore whether HPV-related biomarkers predict oropharyngeal squamous cell cancer (OPSCC) survival similarly across different global regions, and to explore their prognostic utility among non-oropharyngeal (non-OP) head and neck cancers. METHODS: Data from 1362 head and neck SCC (HNSCC) diagnosed 2002-2011 was used from epidemiologic studies in: Brazil (GENCAPO study, n=388), U.S. (CHANCE study, n=472), and Europe (ARCAGE study, n=502). Tumors were centrally tested for p16INK4a and HPV16 DNA (by PCR). Risk of mortality was examined using Cox proportional hazard models. RESULTS: There were 517 OPSCC and 845 non-OP HNSCC. Cases were primarily male (81%), ever smokers (91%), with median age of 58yearsandmedian follow-up of 3.1years (IQR=1.4-5.9). Among OPSCC, the risk of mortality was significantly lower among 184 HPV-related (i.e., p16+/HPV16+) compared to 333 HPV-unrelated (p16- and/or HPV16-) cases (HR=0.25, 95%CI=0.18-0.34). Mortality was reduced among HPV-related OPSCC cases from the U.S., Europe, and Brazil (each p⩽0.01) and after adjustment, remained significantly reduced (aHR=0.34, 95%CI=0.24-0.49). Among non-OP HNSCC, neither p16 (aHR=0.83, 95%CI=0.60-1.14), HPV16 DNA (aHR=1.20, 95%CI=0.89-1.63), or p16+/HPV16+ (aHR=0.59, 95%CI=0.32-1.08) was a significantly predictor of mortality. When interaction was tested, the effect of HPV16/p16 was significantly different in OPSCC than non-OP HNSCC (p-interaction=0.02). CONCLUSION: HPV-related OPSCCs had similar survival benefits across these three regions. Prognostic utility of HPV among non-OP HNSCC is limited so tumor HPV/p16 testing should not be routinely done among non-OP HNSCC. Copyright © 2016 Elsevier Ltd. All rights reserved. KEYWORDS: Brazil; Europe; HNSCC; HPV; Non-OP; Oral HPV; P16; Prognostic; Risk factors; Surviva