Ming-Lan Lu

Protective effect of green tea on the risks of chronic gastritis and stomach cancer

Despite the declining trend, stomach cancer remains the second most common cancer worldwide. We examined the role of green tea consumption on chronic gastritis and stomach cancer risks. A population‐based case‐control study was conducted in Yangzhong, China, with 133 stomach cancer cases, 166 chronic gastritis cases, and 433 healthy controls. Epidemiologic data were collected by standard questionnaire and odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models in SAS. Inverse association was observed between green tea drinking and chronic gastritis and stomach cancer risks. After adjusting for age, gender, education, body mass index, pack‐years of smoking and alcohol drinking, ORs of green tea drinking were 0.52 (95% CI: 0.29–0.94) and 0.49 (95% CI: 0.31–0.77) for stomach cancer and chronic gastritis, respectively. In addition, dose‐response relationships were observed with years of green tea drinking in both diseases. The results provide further support on the protective effect of green tea against stomach cancer. This is the first time that green tea drinking was found to be protective against chronic gastritis, which may be of importance when designing intervention strategies for stomach cancer and its pre‐malignant lesions in the high‐risk population.

GSTP1 polymorphisms and gastric cancer in a high-risk Chinese population

AbstractObjectives: In a population-based case–control study in Yangzhong, China, we investigated the relationship between genetic polymorphisms of GSTP1 and susceptibility to gastric cancer and its premalignant lesion, chronic gastritis. The possible gene–gene interactions between GSTP1 polymorphisms and GSTM1, GSTT1 genes were explored. Methods: Epidemiologic data were collected by standard questionnaire from 133 gastric cancer cases, 166 chronic gastritis cases, and 433 cancer-free population controls. Blood samples for Helicobacter pylori and molecular marker assays were collected from 84 gastric cancer cases, 146 chronic gastritis, and 429 population controls. GSTP1 polymorphisms were determined by the PCR-RFLP method and H. pylori infection was measured by the ELISA method. Associations between certain GSTP1 genotypes and both gastric cancer and chronic gastritis were assessed by odds ratios (ORs) and 95% confidence intervals (CIs) derived from logistic regression. Results: The distributions of three GSTP1 genotypes, Ile/Ile, Ile/Val, and Val/Val, were similar in gastric cancer cases, chronic gastritis, and controls. After adjusting for age, gender, education, body mass index, pack-year of smoking, alcohol drinking, H. pylori infection, salt and fruit intakes, the adjusted ORs of Val/Val were 1.3 (95% CI: 0.1–11.2) for gastric cancer and 0.9 (95% CI: 0.2–4.8) for chronic gastritis. Combining the Val alleles (Val/Val and Ile/Val) into one group, no association was observed between GSTP1 and both gastric cancer and chronic gastritis. In addition, the allelism at the GSTP1 locus did not increase gastric cancer and chronic gastritis risks associated with the GSTM1 or GSTT1 genotypes. Conclusion: Our data suggest that the GSTP1 genotype seems not to be associated with the risk of gastric cancer and chronic gastritis in a high-risk Chinese population.

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.

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.

Joint association of polymorphism of the FGFR4 gene and mutation TP53 gene with bladder cancer prognosis

The impact of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism on bladder cancer is unknown. We found no clear correlations between the FGFR4 genotype and risk of bladder cancer or pathological parameters. Neither the polymorphism nor TP53 mutation status was an independent predictor of prognosis, but they might act jointly on the disease-specific survival of patients.

Uroplakin II Gene is Expressed in Transitional Cell Carcinoma but Not in Bilharzial Bladder Squamous Cell Carcinoma: Alternative Pathways of Bladder Epithelial Differentiation and Tumor Formation

Uroplakins (UPs) are integral membrane proteins that are synthesized as the major differentiation products of mammalian urothelium. We have cloned the human UP-II gene and localized it on chromosome 11q23. A survey of 50 transitional cell carcinomas (TCCs) revealed a UP-II polymorphism but no tumor-specific mutations. Immunohistochemical staining using rabbit antisera against a synthetic peptide of UP-II and against total UPs showed UP reactivity in 39.5% (17 of 43 cases) of conventional TCCs, 12.8% (5 of 39) of bilharzial-related TCCs, and 2.7% (1 of 36) of bilharzial-related squamous cell carcinomas (SCCs). The finding that fewer bilharzial TCCs express UPs than conventional TCCs (12.8 versus 40%) raised the possibility that the former are heterogeneous, expressing SCC features to varying degrees. Our data strongly support the hypothesis that urothelium can undergo at least three pathways of differentiation: (a) urothelium-type pathway; (b) epidermis-type pathway; and (c) glandular-type pathway, characterized by the production of UPs, K1/K10 keratins, and secreted glycoproteins, respectively. Vitamin A deficiency and mesenchymal factors may play a role in determining the relative contributions of these pathways to urothelial differentiation as well as to the formation of TCC, SCC, and adenocarcinoma, or a mixture thereof.