RESUMO
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.
Assuntos
Neoplasias Esofágicas/sangue , Ácido Fólico/sangue , Homocisteína/sangue , Neoplasias Hepáticas/sangue , Neoplasias Gástricas/sangue , Vitamina B 12/sangue , Adulto , Idoso , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
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.
Assuntos
Proteínas de Ciclo Celular/genética , Haplótipos , Neoplasias/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Fumar/efeitos adversos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Desequilíbrio de Ligação , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologiaRESUMO
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.
Assuntos
Inflamação/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Fumar/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Laríngeas/genética , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/genéticaRESUMO
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.
Assuntos
Cromossomos Humanos Par 8/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/etnologia , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Neoplasias/etnologia , Neoplasias Otorrinolaringológicas/etnologia , Neoplasias Otorrinolaringológicas/genética , Risco , Fumar/genética , Neoplasias da Bexiga Urinária/etnologia , Neoplasias da Bexiga Urinária/genéticaRESUMO
In public health, the generation, management, and transfer of knowledge all need major improvement. Problems in generating knowledge include an imbalance in research funding, publication bias, unnecessary studies, adherence to fashion, and undue interest in novel and immediate issues. Impaired generation of knowledge, combined with a dated and inadequate process for managing knowledge and an inefficient system for transferring knowledge, mean a distorted body of evidence available for decisionmaking in public health. This article hopes to stimulate discussion by proposing a Global Registry of Anticipated Public Health Studies. This prospective, comprehensive system for tracking research in public health could help enhance collaboration and improve efficiency. Practical problems must be discussed before such a vision can be further developed.
Assuntos
Pesquisa Biomédica/normas , Saúde Global , Saúde Pública , Sistema de Registros/normas , HumanosRESUMO
Few studies have assessed potential effect modifications by polymorphisms of susceptibility genes on the association between selenium intake and esophageal squamous cell carcinoma (ESCC). We studied the joint effects of dietary selenium and the GSTP1 and p53 polymorphisms on ESCC risk in a population-based case-control study with 218 ESCC cases and 415 controls in Taixing City, China. Dietary selenium intake was estimated from a food frequency questionnaire with 97 food items. GSTP1 and p53 polymorphisms were detected by RFLP-PCR assays. Logistic regression analyses were done to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Reduced ESCC risk was observed among individuals in the highest quartile of dietary selenium intake (adjusted OR, 0.31; 95% CI, 0.13-0.70) with a dose-dependent gradient (P(trend) = 0.01). The p53 Pro/Pro genotype was associated with increased risk of ESCC compared with the Arg/Arg genotype (adjusted OR, 2.02; 95% CI, 1.19-3.42). When combined with selenium consumption, an obvious increased risk was observed among individuals with the p53 Pro/Pro or GSTP1 Ile/Ile genotype with adjusted ORs of 3.19 (95% CI, 1.74-5.84) and 1.90 (95% CI, 1.03-3.51), respectively. Among smokers and alcohol drinkers, elevation of ESCC risk was more prominent among p53 Pro/Pro individuals who consumed a low level of dietary selenium (adjusted OR, 3.59; 95% CI, 1.49-8.66 for smokers and 6.19; 95% CI, 1.83-20.9 for drinkers). Our study suggests that the effect of dietary selenium on the risk of ESCC may be modulated by tobacco smoking, alcohol drinking, and p53 Pro/Pro and GSTP1 Ile/Ile genotypes.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Genes p53 , Glutationa S-Transferase pi/genética , Polimorfismo Genético , Selênio/farmacologia , Idoso , Alcoolismo/complicações , Alcoolismo/genética , Carcinoma de Células Escamosas/fisiopatologia , Dieta , Inquéritos sobre Dietas , Neoplasias Esofágicas/fisiopatologia , Feminino , Genes p53/efeitos dos fármacos , Genótipo , Glutationa S-Transferase pi/efeitos dos fármacos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Risco , Selênio/administração & dosagem , Fumar/efeitos adversos , Fumar/genéticaRESUMO
P53 codon 72 polymorphisms have been reported to be associated with cancers of the lung, esophagus and cervix. However, there have been no reports on the interaction of select risk factors and p53 codon 72 polymorphisms in gastric cancer susceptibility. 155 gastric cancer cases and 134 cancer-free controls were enrolled at the Memorial Sloan Kettering Cancer Center (MSKCC) from November 1992 to November 1994. The crude odds ratio (OR1) associated with the (Pro/Pro) polymorphism and the risk of gastric cancer was 1.27 (0.70-2.33). Adjusting for age, sex, race and education (OR2) and further adjusting for BMI, calories, sodium, smoking, vitamin C, fiber, alcohol, fat, and H. pylori status (OR3) did not yield significant results. Significant joint effects were associated with high fat consumption (OR1=2.61 (95% CI:1.13-6.06); OR2=2.85 (95% CI:1.14-7.15) for total cancers and for proximal tumors (OR1=2.56 (95%CI:1.00-6.54)). The low vitamin C intake/high-risk polymorphism group (Pro/Pro) had an OR1 of 4.82 (95% CI: 1.72-13.45) and the OR2 was 6.19 (95% CI: 2.08-18.40) for distal tumors. The point estimates were increased for interaction odds ratios but not statistically significant (OR1=4.25 (95% CI: 0.66-27.50); OR2=4.73 (95% CI: 0.67-33.43); OR3=5.55 (95% CI: 0.66-46.47)). Further studies specifically looking at proximal and distal tumors are required to confirm any potential interaction between the p53 codon 72 polymorphisms and environmental risk, in particular low dietary vitamin C and high fat consumption.
Assuntos
Códon , Genes p53 , Polimorfismo Genético , Neoplasias Gástricas/genética , Adulto , Idoso , Ácido Ascórbico/administração & dosagem , Estudos de Casos e Controles , Ingestão de Energia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Neoplasias Gástricas/etiologiaRESUMO
AIM: To assess the combinative role of aflatoxin B1(AFB1), cyanobacterial toxins (cyanotoxins), and hepatitis B virus (HBV) x gene in hepatotumorigenicity. METHODS: One-week-old animals carrying HBV x gene and their wild-type littermates were intraperitoneally (ip) injected with either single-dose AFB1 [6 mg/kg body weight (bw)], repeated-dose cyanotoxins (microcystin-LR or nodularin, 10 microg/kg bw once a week for 15 wk), DMSO (vehicle control) alone, or AFB1 followed by cyanotoxins a week later, and were sacrificed at 24 and 52 wk post-treatment. RESULTS: AFB1 induced liver tumors in 13 of 29 (44.8%) transgenic mice at 52 wk post-treatment, significantly more frequent than in wild-type mice (13.3%). This significant difference was not shown in the 24-wk study. Compared with AFB1 exposure alone, MC-LR and nodularin yielded approximately 3-fold and 6-fold increases in the incidence of AFB(1)-induced liver tumors in wild-type animals at 24 wk, respectively. HBV x gene did not further elevate the risk associated with co-exposure to AFB1 and cyanotoxins. With the exception of an MC-LR-dosed wild-type mouse, no liver tumor was observed in mice treated with cyanotoxins alone at 24 wk. Neither DMSO-treated transgenic mice nor their wild-type littermates had pathologic alterations relevant to hepatotumorigenesis in even up to 52 wk. CONCLUSION: HBV x gene and nodularin promote the development of AFB(1)-induced liver tumors. Co-exposure to AFB1 and MC-LR tends to elevate the risk of liver tumors at 24 wk relative to exposure to one of them. The combinative effect of AFB1, cyanotoxins and HBVx on hepatotumorigenesis is weak at 24 wk.
Assuntos
Aflatoxina B1/farmacologia , Toxinas Bacterianas/farmacologia , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Toxinas Marinhas/farmacologia , Venenos/farmacologia , Transativadores/genética , Animais , Carcinoma Hepatocelular/genética , Transformação Celular Neoplásica/patologia , Toxinas de Cianobactérias , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Transgênicos , Microcistinas , Peptídeos Cíclicos/farmacologia , Reação em Cadeia da Polimerase , Fatores de Tempo , Proteínas Virais Reguladoras e AcessóriasRESUMO
Although the incidence of stomach cancer has been declining, it remains the second leading cause of cancer death worldwide. Potential protective effects of allium vegetables against cancer have been reported by a few epidemiologic studies in Chinese populations, but the sample sizes of these studies were relatively small. We examined the associations between allium vegetable consumption and stomach cancer in a large population-based case-control study in Shanghai (750 cases and 750 age- and gender-matched controls) and Qingdao (201 cases and 201 age- and gender-matched controls). Epidemiological data were collected by a standard questionnaire, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression in SAS. After adjusting for matching variables, education, body mass index, pack-years of smoking, alcohol drinking, salt intake, and fruit and vegetable intake, inverse relationships with dose response pattern were observed between frequency of onion intake and stomach cancer in Qingdao (P for trend=0.02) and Shanghai (P for trend=0.04) populations. In Shanghai, negative dose-response relationships were observed between monthly intake of onions (P=0.03) or garlic stalks (P=0.04) and distal, but not cardia cancer. A negative association was also noted between intake of garlic stalks (often vs. never) and risk of stomach cancer in Qingdao (OR=0.30; 95% CI: 0.12-0.77). Our results confirm protective effects of allium vegetables (especially garlic and onions) against stomach cancer.
Assuntos
Allium , Dieta , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/prevenção & controle , Idoso , Estudos de Casos e Controles , China , Estudos Epidemiológicos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , VerdurasRESUMO
OBJECTIVE: To study the relationship between ambient air pollution and daily mortality of SARS in Beijing. METHODS: The approach of time-series Poisson regression was used to assess the relationship between daily SARS mortality, ambient air pollution, and other factors from April 25 to May 31, 2003 in Beijing. RESULTS: An increase of each 10 microg/m3 over a 5-day moving average of PM10, SO2 and NO2 corresponded to 1.06 (1.00-1.12), 0.74 (0.48-1.13) and 1.22 (1.01-1.48) relative risks (RRs) of daily SARS mortality, respectively. The relative risks (RRs) values depended largely on the selection of lag days. CONCLUSION: The daily mortality of SARS might be associated with certain air pollutants in Beijing.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Síndrome Respiratória Aguda Grave/epidemiologia , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , China/epidemiologia , Cidades , Poeira/análise , Monitoramento Ambiental , Monitoramento Epidemiológico , Humanos , Dióxido de Nitrogênio/análise , Tamanho da Partícula , Estudos Retrospectivos , Risco , Síndrome Respiratória Aguda Grave/mortalidade , Dióxido de Enxofre/análiseRESUMO
BACKGROUND: Severe acute respiratory syndrome (SARS) has claimed 349 lives with 5,327 probable cases reported in mainland China since November 2002. SARS case fatality has varied across geographical areas, which might be partially explained by air pollution level. METHODS: Publicly accessible data on SARS morbidity and mortality were utilized in the data analysis. Air pollution was evaluated by air pollution index (API) derived from the concentrations of particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide and ground-level ozone. Ecologic analysis was conducted to explore the association and correlation between air pollution and SARS case fatality via model fitting. Partially ecologic studies were performed to assess the effects of long-term and short-term exposures on the risk of dying from SARS. RESULTS: Ecologic analysis conducted among 5 regions with 100 or more SARS cases showed that case fatality rate increased with the increment of API (case fatality = - 0.063 + 0.001 * API). Partially ecologic study based on short-term exposure demonstrated that SARS patients from regions with moderate APIs had an 84% increased risk of dying from SARS compared to those from regions with low APIs (RR = 1.84, 95% CI: 1.41-2.40). Similarly, SARS patients from regions with high APIs were twice as likely to die from SARS compared to those from regions with low APIs. (RR = 2.18, 95% CI: 1.31-3.65). Partially ecologic analysis based on long-term exposure to ambient air pollution showed the similar association. CONCLUSION: Our studies demonstrated a positive association between air pollution and SARS case fatality in Chinese population by utilizing publicly accessible data on SARS statistics and air pollution indices. Although ecologic fallacy and uncontrolled confounding effect might have biased the results, the possibility of a detrimental effect of air pollution on the prognosis of SARS patients deserves further investigation.
Assuntos
Poluentes Atmosféricos/análise , Síndrome Respiratória Aguda Grave/mortalidade , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , China/epidemiologia , Surtos de Doenças/prevenção & controle , Ecologia , Humanos , Informática em Saúde Pública , Medição de Risco , Síndrome Respiratória Aguda Grave/etiologiaRESUMO
OBJECTIVE: To assess the protective effect of drinking green tea on the development of gastric, liver and esophageal cancers. METHODS: A population based study was conducted in Taixing, Jiangsu province, including 206, 204, 218 cases, respectively, and 415 population controls. RESULTS: Green tea decreased the development of gastric cancer risk by 40%. Dose-response relationships were observed between the length of time, concentration and quantity of green tea drinking and its protective effects on gastric cancer. For individuals who drink green tea for more than 250 g per month, the risk of gastric cancer reduced about 60%. Green tea might have protective effect on liver cancer. However, no protective effect of green tea was observed on esophageal cancer. CONCLUSION: Green tea drinking might be a protective factor for gastric cancer. However, the protective effects of green tea on liver and esophageal cancer were not obvious.
Assuntos
Neoplasias Gástricas/prevenção & controle , Chá/química , Relação Dose-Resposta a Droga , Neoplasias Esofágicas/prevenção & controle , Humanos , Neoplasias Hepáticas/prevenção & controle , Extratos Vegetais/uso terapêuticoRESUMO
One-carbon metabolism (folate metabolism) is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs) in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB) shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71) and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32). There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94). In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity Pâ=â0.005) and stomach cancer (posterior homogeneity Pâ=â0.004), and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity Pâ=â0.021). Among non-alcohol drinkers, the variant allele (allele G) of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of the associations between MTR/MTRR polymorphisms and these cancers indicates potential interactions between alcohol drinking and one-carbon metabolic pathway.
Assuntos
Neoplasias Esofágicas/genética , Ferredoxina-NADP Redutase/genética , Neoplasias Hepáticas/genética , Neoplasias Gástricas/genética , Idoso , Povo Asiático , Estudos de Casos e Controles , China , Neoplasias Esofágicas/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/patologiaRESUMO
Genetic variation at 8q24 is associated with prostate, bladder, breast, colorectal, thyroid, lung, ovarian, UADT, liver and stomach cancers. However, a role for variation at 8q24 in familial clustering of upper gastrointestinal cancers has not been studied. In order to explore potential inherited susceptibility, we analyzed epidemiologic data from a population-based case-control study of upper gastrointestinal cancers from Taixing, China. The study population includes 204 liver, 206 stomach, and 218 esophageal cancer cases and 415 controls. Associations between 8q24 rs1447295, rs16901979, rs6983267 and these cancers were stratified by family history of cancer. Odds ratios and 95% confidence intervals were adjusted for potential confounders: age, sex, education, tobacco smoking, alcohol consumption, and BMI at interview. We also adjusted for hepatitis B and aflatoxin (liver cancer) and Helicobacter pylori (stomach cancer). In a dominant model, among those with a family history of cancer, rs1447295 was positively associated with liver cancer (OR(adj) 2.80; 95% CI 1.15-6.80). Heterogeneity was observed (P(heterogeneity) = 0.029) with rs6983267 and liver cancer, with positive association in the dominant model among those with a family history of cancer and positive association in the recessive model among those without a family history of cancer. When considered in a genetic risk score model, each additional 8q24 risk genotype increased the odds of liver cancer by two-fold among those with a family history of cancer (OR(adj) 2.00; 95% CI 1.15-3.47). These findings suggest that inherited susceptibility to liver cancer may exist in the Taixing population and that variation at 8q24 might be a genetic component of that inherited susceptibility.
Assuntos
Cromossomos Humanos Par 8 , Neoplasias Gastrointestinais/genética , Variação Genética , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Família , Feminino , Neoplasias Gastrointestinais/epidemiologia , Predisposição Genética para Doença , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Common pathogenic mechanisms may be involved in the prevalence of ischemic stroke and coronary heart disease. Recently, genome-wide association (GWA) studies identified a chromosome region (9p21) that confers the risk of coronary heart disease. In a hospital-based case-control study conducted in Chinese Hans, we tested the hypothesis that the methylthioadenosine phosphorylase (MTAP) gene on chromosome region 9p21 is involved in the aetiology of ischemic stroke using a tagging single nucleotide polymorphism (tSNP) strategy. We observed significant association of rs10118757 in the MTAP gene with ischemic stroke. The G allele of rs10118757 was associated with an increased risk of stroke, with a per-allele OR of 1.31(95% CI, 1.04-1.65, p=0.025). The association remains after controlling for confounding factors including age, gender, body mass index, smoking, alcohol drinking, hypertension, diabetes, and hyperlipidaemia (OR=1.38, 95 CI, 1.02-1.88, p=0.039). In addition, the GA+GG genotype of rs10118757 was associated with the increased risk of an undetermined subtype of ischemic stroke (OR=2.14, 95 CI, 1.35-3.38, p=0.001). Further, we also observed the combined effects of rs10118757 with alcohol drinking and hypertension, which increased the risk of ischemic stroke. Our observations support the hypothesis that the MTAP gene may be involved in the prevalence of ischemic stroke in Chinese Hans.
Assuntos
Isquemia Encefálica/genética , Etnicidade/genética , Polimorfismo de Nucleotídeo Único , Purina-Núcleosídeo Fosforilase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Alelos , Isquemia Encefálica/classificação , Isquemia Encefálica/etnologia , Estudos de Casos e Controles , China/epidemiologia , Comorbidade , Fatores de Confusão Epidemiológicos , Diabetes Mellitus/epidemiologia , Feminino , Haplótipos/genética , Humanos , Hiperlipidemias/epidemiologia , Hipertensão/epidemiologia , Embolia Intracraniana/etnologia , Embolia Intracraniana/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Fumar/epidemiologiaRESUMO
BACKGROUND: Longevity is a multifactorial trait with a genetic contribution, and mitochondrial DNA (mtDNA) polymorphisms were found to be involved in the phenomenon of longevity. METHODOLOGY/PRINCIPAL FINDINGS: To explore the effects of mtDNA haplogroups on the prevalence of extreme longevity (EL), a population based case-control study was conducted in Rugao--a prefecture city in Jiangsu, China. Case subjects include 463 individuals aged > or = 95 yr (EL group). Control subjects include 926 individuals aged 60-69 years (elderly group) and 463 individuals aged 40-49 years (middle-aged group) randomly recruited from Rugao. We observed significant reduction of M9 haplogroups in longevity subjects (0.2%) when compared with both elderly subjects (2.2%) and middle-aged subjects (1.7%). Linear-by-linear association test revealed a significant decreasing trend of N9 frequency from middle-aged subjects (8.6%), elderly subjects (7.2%) and longevity subjects (4.8%) (p = 0.018). In subsequent analysis stratified by gender, linear-by-linear association test revealed a significant increasing trend of D4 frequency from middle-aged subjects (15.8%), elderly subjects (16.4%) and longevity subjects (21.7%) in females (p = 0.025). Conversely, a significant decreasing trend of B4a frequency was observed from middle-aged subjects (4.2%), elderly subjects (3.8%) and longevity subjects (1.7%) in females (p = 0.045). CONCLUSIONS: Our observations support the association of mitochondrial DNA haplogroups with exceptional longevity in a Chinese population.
Assuntos
DNA Mitocondrial/genética , Haplótipos , Longevidade , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
In a hospital based case control study, we investigated the association of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene, cyclin-dependent kinase inhibitor 2B (CDKN2B) gene, and two genetic variants (rs10757274 and rs2383206) on chromosome region 9p21 with ischemic stroke in Chinese Hans. Two polymorphisms in the CDKN2A gene (rs3088440 and rs3731245) and two polymorphisms in the CDKN2B gene (rs3217992 and rs1063192) were selected by using a strategy of tagging single nucleotide polymorphisms (tSNP). We observed significant association of rs2383206 with ischemic stroke. Subjects with the GG/GA genotype of rs2383206 had a 1.51-fold (95%CI 1.11-2.05, p=0.009) increased risk of stroke, compared with those with the AA genotype. In addition, the GG/GA genotypes of rs2383206 and rs3731245 was associated with an increased risk of large vessel subtype and small vessel subtype of ischemic stroke, respectively, with ORs of 2.09 (95%CI 1.30-3.37, p=0.002) and 1.63 (95%CI 1.06-2.51, p=0.026), respectively. In gene-environmental interaction analysis, elevation of ischemic stroke risk was observed among AG+GG genotype carriers who consume alcohol, smoke cigarette, and have hypertension, with adjusted combined ORs of 2.86(1.51-5.41), 4.30(2.38-7.77), and 13.97(7.78-25.07), respectively, compared with low-risk individuals for rs2383206 (GG carriers who did not consume alcohol, smoke cigarette, and without hypertension). We provide evidence that genetic variants on chromosome region 9p21 may implicated in the prevalence of ischemic stroke in Chinese.
Assuntos
Isquemia Encefálica/genética , Cromossomos Humanos Par 9 , Inibidor de Quinase Dependente de Ciclina p15/genética , Genes p16 , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/epidemiologia , Isquemia Encefálica/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fumar/epidemiologia , Acidente Vascular Cerebral/epidemiologiaRESUMO
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.
Assuntos
Ciclo-Oxigenase 2/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Predisposição Genética para Doença , Fenômenos do Sistema Imunitário/genética , Proteínas Nucleares/genética , Neoplasias Gástricas/genética , Fatores de Transcrição/genética , Estudos de Casos e Controles , China , Feminino , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/imunologiaRESUMO
OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR), which is expressed in the liver, may be involved in both DNA methylation and DNA synthesis. It is also indicated as a potential risk factor of liver cancer in patients with chronic liver disease. To date, no study has been conducted on MTHFR and hepatocellular carcinoma (HCC) using a population-based design. The objective of this study was to evaluate the effects of polymorphisms of the MTHFR gene on the risk of primary liver cancer and their possible effect modifications on various environmental risk factors. METHODS: A population-based case-control study was conducted in Taixing, China. MTHFR C677T and A1298C were assayed by PCR-RFLP techniques. RESULTS: The frequency of MTHFR 677 C/C wild homozygotes genotype was 25.8% in cases, which was lower than that in controls (34.5%). The adjusted odds ratios (ORs) for the MTHFR 677 C/T and T/T genotype were 1.66(95% CI: 1.06-2.61), 1.21(95% CI: 0.65-2.28) respectively when compared with the MTHFR 677 C/C genotype. Subjects carrying any T genotype have the increased risk of 1.55(95% CI: 1.01-2.40) for development of primary hepatocellular carcinoma. A high degree of linkage disequilibrium was observed between the C677T and A1298C polymorphisms, with the D' of 0.887 and p < 0.01. The MTHFR 677 any T genotype was suggested to have potentially more than multiplicative interactions with raw water drinking with p-value for adjusted interaction of 0.03. CONCLUSION: We observed that the MTHFR 677 C/T genotype was associated with an increased risk of primary liver cancer in a Chinese population. The polymorphism of MTHFR 677 might modify the effects of raw water drinking on the risk of primary hepatocellular carcinoma.