Z. Wang

Etiological study of esophageal squamous cell carcinoma in an endemic region: a population-based case control study in Huaian, China

BackgroundContinuous exposure to various environmental carcinogens and genetic polymorphisms of xenobiotic-metabolizing enzymes (XME) are associated with many types of human cancers, including esophageal squamous cell carcinoma (ESCC). Huaian, China, is one of the endemic regions of ESCC, but fewer studies have been done in characterizing the risk factors of ESCC in this area. The aims of this study is to evaluate the etiological roles of demographic parameters, environmental and food-borne carcinogens exposure, and XME polymorphisms in formation of ESCC, and to investigate possible gene-gene and gene-environment interactions associated with ESCC in Huaian, China.MethodsA population based case-control study was conducted in 107 ESCC newly diagnosed cases and 107 residency- age-, and sex-matched controls in 5 townships of Huaian. In addition to regular epidemiological and food frequency questionnaire analyses, genetic polymorphisms of phase I enzymes CYP1A1, CYP1B1, CYP2A6, and CYP2E1, and phase II enzymes GSTM1, GSTT1, GSTP1, and microsomal epoxide hydrolase (EPHX) were assessed from genomic DNA using PCR based techniques.ResultsConsuming acrid food, fatty meat, moldy food, salted and pickled vegetables, eating fast, introverted personality, passive smoking, a family history of cancer, esophageal lesion, and infection with Helicobacter pylori were significant risk factors for ESCC (P < 0.05). Regular clean up of food storage utensils, green tea consumption, and alcohol abstinence were protective factors for ESCC (P < 0.01). The frequency of the GSTT1 null genotype was higher in cases (59.4%) compared to controls (47.2%) with an odds ratio (OR) of 1.68 and 95% confidence interval (CI) from 0.96 to 2.97 (P = 0.07), especially in males (OR = 2.78; 95% CI = 1.22–6.25; P = 0.01). No associations were found between polymorphisms of CYP1A1, CYP1B1, CYP2A6, CYP2E1, GSTM1, GSTP1, and EPHX and ESCC (P > 0.05).ConclusionOur results demonstrated that dietary and environmental exposures, some demographic parameters and genetic polymorphism of GSTT1 may play important roles in the development of ESCC in Huaian area, China.

NovaSil clay does not affect the concentrations of vitamins A and E and nutrient minerals in serum samples from Ghanaians at high risk for aflatoxicosis

To assess the potential interference of NovaSil (NS) clay with micronutrients in humans, vitamins A and E and minerals (15 nutrient and 15 non-nutrient minerals) were measured in serum samples from a 3-month intervention trial with NS. Participants (nu2009=u2009177) were randomly divided into three groups that received 3.0 g NS day−1 (high dose, HD), 1.5 g NS day−1 (low dose, LD), or placebo (PL). Levels of vitamins A and E in serum were comparable among the three study groups at baseline, 1 month and 3 months of NS intervention. Gender-stratified non-parametric mixed-effect model analysis showed no significant effects of dose and dose–time interaction for levels of vitamins A and E. A significant time effect was detected; however, it was limited to an increase in vitamin E in the male participants over the course of the study. No significant differences were found in levels of the nutrient and non-nutrient minerals between the HD and PL groups at baseline and 3 months of NS intervention, except for strontium levels. Strontium was significantly increased (pu2009<u20090.001) in the HD group (maleu2009=u2009113.65u2009±u200928.00 µg l−1; femaleu2009=u2009116.40u2009±u200924.26 µg l−1) compared with the PL group (maleu2009=u200983.55u2009±u200939.90 µg l−1; femaleu2009=u200990.47u2009±u200925.68 µg l−1) following the 3-month intervention with NS. These results, combined with safety and efficacy data, confirm that NS clay is highly effective in reducing aflatoxin exposure and acts as a selective enterosorbent that does not affect the serum concentrations of important vitamins and nutrient minerals in humans.

Aflatoxin-albumin adducts and correlation with decreased serum levels of vitamins A and E in an adult Ghanaian population.

A study of aflatoxin (AF) exposure and the levels of vitamins A and E was carried out with a group of 507 Ghanaian participants. AFB1–albumin adducts (AFB-AA) were measured by radioimmunoassay and vitamins A and E were measured by high-performance liquid chromatography (HPLC). The average level of serum AFB-AA was 0.94 ± 0.64 (range = 0.1–4.44) pmol mg−1 albumin. Mean levels of vitamins A and E were 1.32 ± 0.48 (range = 0.41–4.85) µmol l−1 and 15.68 ± 4.12 (range = 6.35–30.40) µmol l−1, respectively. A significantly negative correlation was found between serum AFB-AA and vitamin A levels (r = −0.110, p = 0.013). An even stronger, significant negative, correlation was found between serum AFB-AA and vitamin E levels (r = −0.149, p < 0.001). Serum AFB-AA levels were statistically higher (median = 0.985 pmol mg−1 albumin) in subjects who had low levels of both vitamins A and E as compared with the levels (median = 0.741 pmol mg−1 albumin) subjects who had high vitamins A and E levels (p trend = 0.001). To verify these findings, blood samples were again collected from 165 of the 507 people 3 months after the initial collection. Significantly negative correlations were confirmed between levels of serum AFB-AA and both vitamins A (r = −0.232, p = 0.003) and E (r = −0.178, p = 0.023). Again, high serum AFB-AA concentrations (median = 1.578 pmol mg−1 albumin) were found in subjects with low levels of vitamins A and E compared with the concentrations (median = 1.381 pmol mg−1 albumin) in subjects with high levels of vitamins A and E (p trend = 0.002). These data show that AF exposure was associated with decreased levels of serum vitamins A and E in high-risk human populations, which may significantly influence the incidence of AF-related adverse health effects.

Seasonal variations in the concentration of microcystin‐LR in two lakes in western Texas, USA

Seasonal variations in the concentration of microcystin-LR (MCLR) in Buffalo Springs Lake (BSL) and Lake Ransom Canyon (LRC; both locations in Lubbock, TX, USA) were monitored from 2003 to 2004. In BSL, the average concentrations of MCLR were 1.78 +/- 1.43 microg/L (mean +/- SD; range, 0.177-4.914 microg/L) in spring, 0.41 +/- 0.096 microg/L (range, 0.191-0.502 microg/L) in summer, 0.46 +/- 0.41 microg/L (range, 0.205-1.598 microg/L) in fall, and 1.04 +/- 0.71 microg/L (range, 0.096-2.428 microg/L) in winter. In LRC, the corresponding concentrations were 1.08 +/- 1.29 microg/L (range, 0.2-5.83 microg/L) in spring, 0.83 +/- 0.46 microg/L (range, 0.315-1.671 microg/L) in summer, 0.44 +/- 0.03 microg/L (range, 0.368-0.555 microg/L) in fall, and 0.78 +/- 0.52 microg/L (range, 0.225-2.130 microg/L) in winter. In both lakes, the seasonal fluctuation of MCLR concentrations correlated positively with dissolved oxygen and negatively with temperature and pH.

Abstract 1860: Association of esophageal cancer risk with genetic polymorphisms of xenobiotic metabolizing genes, DNA repair genes, and inflammation-regulating genes in Huaian, China

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DCnnAccumulating evidences suggest that both exposure to environmental carcinogens and individual susceptibility factors contribute to the formation of esophageal cancer. Huaian City is one of the highest risk areas of esophageal cancer in China with the annual incidence over 100/100,000 people. To explore etiological risk factors contributing to the high rate of esophageal cancer, a population-based case-control study was conducted in 185 esophageal squamous cell carcinoma (ESCC) cases and 515 age-, gender-, and residency-matched healthy controls in Huaian. Our previous study found an association between dietary fumonisin exposure and ESCC risk in this population. In the present study, we further investigated the association between ESCC and polymorphic genes involving in xenobiotic metabolizing activities, DNA repair, and inflammation regulation including GSTM1, GSTT1, XPD (Lys751Gln), hOGG1 (Ser326Cys), TNF-α (G308A), NF-κB (−94ins/delATTG), COX-2 (G765C), and iNOS (Ser608Leu). Genetic polymorphisms of GSTM1 and GSTT1 were determined by multiplex PCR and other polymorphisms were determined by PCR-restriction fragment length polymorphism (RFLP) analysis using genomic DNA samples obtained from lymphocytes of study subjects. The prevalence of GSTT1 null genotype was significantly higher in cases (53.51%) than in controls (41.94%) (p=0.0067), with an age- and gender-adjusted odds ratio (OR) of 1.68 and 95% confidence interval (CI) of 1.18 − 2.39. After stratifying by gender, GSTT1 null type was found more prevalent in male cases (57.14%) than in male controls (42.64%) (p=0.0117). XPD Lys751Gln polymorphism was associated with increased ESCC risk (age- and gender-adjusted OR=1.74, 95% CI: 1.11-2.74). XPD heterozygous and mutant genotypes (Lys/Gln+Gln/Gln) were more prevalent in cases (20.54%) than in controls (14.26%) (p=0.0453), and in female cases (24.32%) than in female controls (13.01%) (p=0.0187). Heterozygous genotype of TNF-α was found in 12.97% of cases and 7.65% of controls, showing a marginal increased risk of ESCC (adjusted OR=1.68, 95% CI: 0.95-2.98). These results suggest that polymorphisms of GSTT1, XPD and TNF-α gene may contribute to ESCC risk in this high-risk population. (Supported by NIH/NCI grants, CA94683 and CA90997).nnNote: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.nnCitation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1860.