Bao-Guo Ding

Green tea drinking and multigenetic index on the risk of stomach cancer in a Chinese population

The purpose of our study was to examine the roles of green tea drinking, other risk and protective factors, and polymorphism of susceptibility genes such as GSTM1, GSTT1, GSTP1, and p53 codon 72 and their possible joint effects on the risk of stomach cancer. A population‐based case‐control study was conducted in Taixing, China, including 206 newly diagnosed cases with stomach cancer and 415 healthy control subjects. Epidemiological data were collected by in‐person interviews using a standard questionnaire. Polymorphisms of susceptibility genes were assayed by PCR‐RFLP techniques. A multigenetic index was created by summing up the number of risk genotypes. The data were analyzed using the logistic regression model. A reverse association between green tea drinking and risk of stomach cancer was observed with an adjusted odds ratio (OR) of 0.59 (95% confidence interval [CI] = 0.34–1.01). Dose‐response relationship was shown (p‐trend < 0.05). A higher score on the multigenetic index was associated with increased risk of stomach cancer with an adjusted OR of 2.21 (95% CI = 1.02–4.79) for those with at least 3 risk genotypes compared to those with <2 risk genotypes. Green tea drinking was suggested to have more than multiplicative interactions with alcohol consumption with an adjusted OR for interaction of 4.57 (95% CI = 1.62–12.89), and with higher multigenetic index with adjusted OR for interaction of 2.31 (95% CI = 0.88–6.03). The protective effect of green tea drinking was observed on the risk of stomach cancer and the possible effect modification by susceptibility genes was suggested.

Associations between Variants of the 8q24 Chromosome and Nine Smoking-Related Cancer Sites

Recent genome-wide association studies identified key single nucleotide polymorphisms (SNPs) in the 8q24 region to be associated with prostate cancer. 8q24 SNPs have also been associated with colorectal cancer, suggesting that this region may not be specifically associated to just prostate cancer. To date, the association between these polymorphisms and tobacco smoking-related cancer sites remains unknown. Using epidemiologic data and biological samples previously collected in three case-control studies from U.S. and Chinese populations, we selected and genotyped one SNP from each of the three previously determined “regions” within the 8q24 loci, rs1447295 (region 1), rs16901979 (region 2), and rs6983267 (region 3), and examined their association with cancers of the lung, oropharynx, nasopharynx, larynx, esophagus, stomach, liver, bladder, and kidney. We observed noteworthy associations between rs6983267 and upper aerodigestive tract cancers [adjusted odds ratio (ORadj), 1.69; 95% confidence interval (95% CI), 1.28-2.24], particularly in oropharynx (ORadj, 1.80; 95% CI, 1.30-2.49) and larynx (ORadj, 2.04; 95% CI, 1.12-3.72). We also observed a suggestive association between rs6983267 and liver cancer (ORadj, 1.51; 95% CI, 0.99-2.31). When we stratified our analysis by smoking status, rs6983267 was positively associated with lung cancer among ever-smokers (ORadj, 1.45; 95% CI, 1.05-2.00) and inversely associated with bladder cancer among ever-smokers (ORadj, 0.35; 95% CI, 0.14-0.83). Associations were observed between rs16901979 and upper aerodigestive tract cancer among never-smokers and between rs1447295 and liver cancer among ever-smokers. Our results suggest variants of the 8q24 chromosome may play an important role in smoking-related cancer development. Functional and large epidemiologic studies should be conducted to further investigate the association of 8q24 SNPs with smoking-related cancers. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3193–202)

Associations between NBS1 polymorphisms, haplotypes and smoking-related cancers.

Constituents of tobacco smoke can cause DNA double-strand breaks (DSBs), leading to tumorigenesis. The NBS1 gene product is a vital component in DSB detection and repair, thus genetic variations may influence cancer development. We examined the associations between NBS1 polymorphisms and haplotypes and newly incident smoking-related cancers in three case-control studies (Los Angeles: 611 lung and 601 upper aero-digestive tract (UADT) cancer cases and 1040 controls; Memorial Sloan-Kettering Cancer Center: 227 bladder cancer cases and 211 controls and Taixing, China: 218 esophagus, 206 stomach, 204 liver cancer cases and 415 controls). rs1061302 was associated with cancers of the lung [adjusted odds ratio (OR(adj)) = 1.6, 95% confidence interval (CI): 1.2, 2.4], larynx (OR(adj) = 0.56, 95% CI: 0.32, 0.97) and liver (OR(adj) = 1.7, 95% CI: 1.0, 2.9). Additionally, positive associations were found for rs709816 with bladder cancer (OR(adj) = 4.2, 95% CI: 1.4, 12) and rs1063054 with lung cancer (OR(adj) = 1.6, 95% CI: 1.0, 2.3). Some associations in lung and stomach cancers varied with smoking status. CAC haplotype was positively associated with smoking-related cancers: lung (OR(adj) = 1.7, 95% CI: 1.1, 2.9) and UADT (OR(adj) = 2.0, 95% CI: 1.1, 3.7), specifically, oropharynx (OR(adj) = 2.1, 95% CI: 1.0, 4.2) and larynx (OR(adj) = 4.8, 95% CI: 1.7, 14). Bayesian false-discovery probabilities were calculated to assess Type I error. It appears that NBS1 polymorphisms and haplotypes may be associated with smoking-related cancers and that these associations may differ by smoking status. Our findings also suggest that single-nucleotide polymorphisms located in the binding region of the MRE-RAD50-NBS1 complex or microRNA targeted pathways may influence tumor development. These hypotheses should be further examined in functional studies.

Green tea consumption, inflammation and the risk of primary hepatocellular carcinoma in a Chinese population

OBJECTIVE Green tea has been found to possess anti-inflammatory, anti-oxidative and anti-carcinogenic properties. The present study examines the association between green tea drinking and hepatocellular carcinoma (HCC) and its interactions with other risk or protective factors and single nucleotide polymorphisms (SNP) of inflammation and oxidative stress related genes. METHODS A population-based case-control study with 204 primary HCC cases and 415 healthy controls was conducted in Taixing, China. Epidemiological data were collected using a standard questionnaire. SNPs of genes of the inflammation and metabolic pathways were genotyped at the UCLA Molecular Epidemiology Laboratory. Logistic regression was performed to estimate adjusted odds ratios and 95% confidence intervals. RESULTS Longer duration and larger quantities of green tea consumption were inversely associated with primary HCC. Individuals who drank green tea longer than 30 years were at lowest risk (adjusted OR=0.44, 95% CI: 0.19-0.96) compared with non-drinkers. A strong interaction was observed between green tea drinking and alcohol consumption (adjusted OR for interaction=3.40, 95% CI: 1.26-9.16). Green tea drinking was also observed to have a potential effect modification on HBV/HCV infection, smoking and polymorphisms of inflammation related cytokines, especially for IL-10. CONCLUSION Green tea consumption may protect against development of primary HCC. Potential effect modifications of green tea on associations between primary HCC and alcohol drinking, HBV/HCV infection, and inflammation-related SNPs were suggested.

Dietary mineral and trace element intake and squamous cell carcinoma of the esophagus in a chinese population

Abstract: Few studies have been conducted in low-selenium areas of China to assess the relationships between dietary intake of selenium and zinc and the risk of squamous cell carcinoma of the esophagus (SCCE). We studied dietary mineral and trace element intake and risk of SCCE in a population- based, case-control study in Taixing, China, in 2000. A total of 218 SCCE patients and 415 population healthy controls were interviewed using a standard dietary and health questionnaire. The median and quartiles were calculated to represent the average level and distribution of selected dietary minerals and trace elements estimated by the Chinese Standard Tables of Food Composition. The adjusted odds ratios (ORs) comparing the highest with the lowest quartiles were 0.30 (95% confidence intervals, CIs = 0.13–0.67) for selenium intake and 0.28 (95% CI = 0.11–0.70) for zinc intake with obvious dose-dependent patterns (P values for trend = 0.01). The adjusted OR for the combined effect of selenium and zinc intake was 0.53 (95% CI = 0.29–0.96) after controlling for potential confounding factors, including age, gender, educational level, body mass index, and total energy intake. Our results suggested that the potential joint effect of zinc and selenium might contribute to SCCE risk. Increased dietary intake of selenium and zinc may decrease the risk of SCCE in a low-selenium area of China.

Single nucleotide polymorphisms of 8 inflammation-related genes and their associations with smoking-related cancers

Tobacco smoke and its metabolites are carcinogens that increase tissue oxidative stress and induce target tissue inflammation. We hypothesized that genetic variation of inflammatory pathway genes plays a role in tobacco‐related carcinogenesis and is modified by tobacco smoking. We evaluated the association of 12 single nucleotide polymorphisms of 8 inflammation‐related genes with tobacco‐related cancers (lung, oropharynx, larynx, esophagus, stomach, liver, bladder, and kidney) using 3 case‐control studies from: Los Angeles (population‐based; 611 lung and 553 upper aero‐digestive tract cancer cases and 1,040 controls), Taixing, China (population‐based; 218 esophagus, 206 stomach, 204 liver cancer cases, and 415 controls), and Memorial Sloan‐Kettering Cancer Center (hospital‐based; 227 bladder cancer cases and 211 controls). After adjusting for age, education, ethnicity, gender, and tobacco smoking, IL10 rs1800871 was inversely associated with oropharyngeal cancer (CT+TT vs. CC adjusted odds ratio [aOR]: 0.69, 95% confidence interval [CI]: 0.50–0.95), and was positively associated with lung cancer among never smokers (TT vs. CT+CC aOR: 2.5, 95% CI: 1.3–5.1) and inversely with oropharyngeal cancer among ever smokers (CT+TT vs. CC aOR: 0.63, 95% CI: 0.41–0.95). Among all pooled never smokers (588 cases and 816 controls), TNF rs1799964 was inversely associated with smoking‐related cancer (CC vs. CT+TT aOR: 0.36, 95% CI: 0.17–0.77). Bayesian correction for multiple comparisons suggests that chance is unlikely to explain our findings (although epigenetic mechanisms may be in effect), which support our hypotheses, suggesting that IL10 rs1800871 is a susceptibility marker for oropharyngeal and lung cancers, and that TNF rs1799964 is associated with smoking‐related cancers among never smokers.

Genetic Variation in Immune Regulation and DNA Repair Pathways and Stomach Cancer in China

The incidence of stomach cancer is high in certain parts of the world, particularly in China. Chronic Helicobacter pylori infection is the main risk factor, yet the vast majority of infected individuals remain unaffected with cancer, suggesting an important role of other risk factors. We conducted a population-based case-control study including 196 incident stomach cancer cases and 397 matched controls to test the hypothesis that adverse single nucleotide polymorphism (SNP) genotypes and haplotypes within genes of the DNA repair and immune regulatory pathways are associated with increased stomach cancer risk. Genomic DNA isolated from blood samples was used for genotyping, and results were obtained for 57 putatively functional SNPs in 28 genes. Odds ratios (OR) and 95% confidence intervals (95% CI) were obtained from adjusted logistic regression models. For PTGS2, a gene involved in the inflammatory response, associations with stomach cancer risk were observed for TC genotype carriers of rs5279 (OR, 0.24; 95% CI, 0.08-0.73), CT genotype carriers of the 3′-untranslated region SNP rs689470 (OR, 7.49; 95% CI, 1.21-46.20), and CTTC haplotype carriers of rs5277, rs5278, rs5279, and rs689470 (OR, 0.41; 95% CI, 0.18-0.95). For ERCC5, a gene involved in nucleotide excision repair, TC genotype carriers of rs1047768 (OR, 0.65; 95% CI, 0.41-1.03), GC genotype carriers of the nonsynonymous SNP rs2227869 (OR, 0.30; 95% CI, 0.13-0.67), and CCG haplotype carriers of rs1047768, rs17655, and rs2227869 (OR, 0.45; 95% CI, 0.20-1.04) were associated with reduced stomach cancer risk. In conclusion, PTGS2 and ERCC5 were associated with stomach cancer risk in a Chinese population. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2304–9)

Polymorphisms of 5,10-methylenetetralydrofolate reductase (MTHFR), fruit and vegetable intake, and the risk of stomach cancer

Abstract Stomach cancer is a serious public health problem in China. 5,10-Methylenetetralydrofolate reductase (MTHFR) may be involved in both DNA methylation and DNA synthesis. Folate deficiency is associated with cancer risk that may be modulated by a genetic variation in the MTHFR gene in folate metabolism. The main goal of this study was to evaluate the association between polymorphisms of the MTHFR gene and the risk of stomach cancer. This study also explored the modification effects of fruit and vegetable intake (one of the main constituents is folate) on the risk of this disease. A population-based case-control study was conducted in Taixing, China, consisting of 206 newly diagnosed cases with primary stomach cancer and 415 healthy population controls. Polymorphisms of MTHFR C677T and A1298C were assayed by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) techniques. The data were analysed using the logistic regression model. No obvious association between the MTHFR A1298C polymorphism and the risk of stomach cancer was observed in this study. The frequencies of 677 C/C, C/T, and T/T were 34.5, 50.9, and 14.6%, respectively, in controls. The frequency of the MTHFR 677 wild homozygotic genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratio (OR) for the MTHFR 677 any T genotype was 2.05 (95% confidence interval (CI), 1.26–3.34) when compared with the C/C genotype. In the low fruit and vegetable intake group an increasing trend was observed with the T allele exposure, p=0.0056. The adjusted ORs were 1.68 (95% CI = 0.86–3.29) for the C/T genotype and 3.58 (95% CI = 1.46–8.75) for the T/T genotype, respectively. The MTHFR 677 any T genotype was associated with an increased risk of primary stomach cancer among the Chinese population. Folate deficiency might modify the MTHFR gene polymorphism and influence the risk of stomach cancer.

HBV Infection and Familial Aggregation of Liver Cancer: An Analysis of Case-Control Family Study

AbstractObjectives: Hepatitis B virus (HBV) infection is one of the most important risk factors for hepatocellular carcinoma (HCC). The specific aim of this study is to assess the influence of HBV infection on familial aggregation of HCC. Methods: We conducted a population-based case-control family study of liver cancer in Taixing, China, in 2001-2002, with a total of 3611 individuals from 202 case families and 202 control families. Conditional logistic regression was used for the case-control data. The approach of GEE2 was used to analyze the family data and age and sex were adjusted in all marginal regression models. Results: The odds ratio for HBV associated with HCC was 41.39 (95% confidence interval (CI): 23.03-74.30). The relatives of cases had a higher risk of liver cancer compared with the relatives of controls with a conditional odds-ratio of 3.06 (95% CI: 1.48-6.33). The association parameters among first- and second-degree relatives were no longer statistically significant when HbsAg was taken into consideration. Conclusion: HBV infection was likely a main reason for the familial aggregation of liver cancer in Southern China.

Plasma Folate, Vitamin B12, and Homocysteine and Cancers of the Esophagus, Stomach, and Liver in a Chinese Population

Evidence is accumulating regarding a role of micronutrients in folate metabolism in cancer risk. We investigated the associations of plasma folate, vitamin B12, and homocysteine with upper gastrointestinal (GI) cancers in a population-based case-control study in Taixing City, China. With informed consent, we recruited cases with cancers of esophagus (n = 218), stomach (n = 206), and liver (n = 204), and one common healthy control group (n = 405). A standardized epidemiologic questionnaire was used in face-to-face interviews, and blood samples were collected during interviews. We observed an inverse association between plasma folate levels and liver cancer. The adjusted odds ratio (aOR) was 0.46 [95% confidence interval (CI) = 0.24–0.88] comparing individuals in the highest quartile to those in the lowest. We found a positive association between plasma vitamin B12 levels and all three cancers. The aORs for those in the highest quartile were 2.80 (95% CI = 1.51–5.18) for esophageal cancer, 2.17 (1.21–3.89) for stomach cancer, and 9.97 (4.82–20.60) for liver cancer, comparing to those in the lowest quartile. We further observed interaction between plasma folate and vitamin B12 on these cancers. Our data indicated associations between plasma folate and vitamin B12 with upper GI cancers in Chinese population. Further research is warranted considering the debate over the necessity of food fortification.