Biomedical subjects

Jian-Min Yuan

Publications and source records attributed to Jian-Min Yuan.

At least 19 recordsLinked to original sources

PubMed2007

Urinary biomarkers of tea polyphenols and risk of colorectal cancer in the Shanghai Cohort Study.

There have been no studies on specific tea polyphenol biomarkers and risk of colorectal cancer in humans. We prospectively examined the associations between validated biomarkers of specific tea polyphenols and risk of developing colorectal cancer among a cohort of 18,244 men in Shanghai, China, with 16 years of follow-up. Epigallocatechin (EGC), 4'-O-methyl-epigallocatechin (4'-MeEGC) and epicatechin, and their metabolites in baseline urine samples were measured on 162 incident colorectal cancer cases and 806 matched controls. Individuals with high prediagnostic urinary EGC levels had a lower risk of colon cancer. Compared with undetectable EGC, odds ratios (95% confidence interval) for colon cancer in the lowest, intermediate and highest tertile of detectable EGC were 0.64 (0.33-1.24), 0.60 (0.30-1.20) and 0.40 (0.19-0.83), respectively (p for trend = 0.02). A similar inverse relation between 4'-MeEGC and colon cancer also was observed. Compared with the lowest quartile, odds ratios (95% confidence intervals) for colon cancer in the 2nd, 3rd and 4th quartiles of urinary 4'-MeEGC were 0.49 (0.25-0.96), 0.32 (0.16-0.67) and 0.41 (0.20-0.84), respectively (p for trend = 0.006). The strongest protective effect was seen for regular tea drinkers who showed high levels of urinary EGC and 4'-MeEGC. No association between urinary levels of epicatechin or its metabolite and colon cancer risk was observed. Urinary levels of tea polyphenols and their metabolites were not associated with rectal cancer risk. The present study supports the notion of tea catechins as chemopreventive agents against the development of colon cancer in humans.

Biomarkers↗

PubMed2006

Time-dependent sensitivity analysis of biological networks: coupled MAPK and PI3K signal transduction pathways.

Sensitivity analysis has been widely used in the studies of complicated chemical reaction and biological networks, for example, in combustion studies and metabolic control analysis of pathways. In the latter cases, the responses of system properties at steady states with respect to changes of parameters, such as initial concentrations and rate constants, are often expressed as sensitivities. Besides steady-state sensitivities, time-dependent sensitivities should be useful; however, the explicit use of them in analyzing complicated biological systems has so far been limited. Using the coupled mitogen activated protein kinase (MAPK)-phophatidylinoisitol 3'-kinase (PI3K) system of the Ras pathways, known to be involved in about 30% of human cancers, as an example, we show that time-dependent sensitivities are useful for the studies of complex biological systems. They provide, for example, the following information: (a) multiple time scales existing in a complex system involving cross-talks and feedback loops; (b) the signs and strengths of responses to perturbations (as system complication increases, the signs of global responses are not always easily determined; for example, response may change sign more than once as time evolves); (c) beyond concentration dynamics, sensitivities revealing further details about the intricate dynamics and the effects of the cross-talks; (d) ranking of vulnerability of nodes of a biological network using integrated sensitivity-a first step toward the identification of drug targets; (e) reduced sensitivity serving as a measure of the stability or robustness of pathways. Our results indicate that the role of the PI3K branch in the coupled pathways is to enhance the robustness of the MAPK pathway. More importantly, they demonstrate that time-dependent sensitivity analysis can be a valuable tool in system biology.

Mitogen-Activated Protein Kinases↗

PubMed2006

Green tea, black tea and colorectal cancer risk: a meta-analysis of epidemiologic studies.

Experimental studies have supported tea as a chemopreventive agent for colorectal cancer. No quantitative summary of the epidemiologic evidence on tea and colorectal cancer risk has ever been performed. The current meta-analysis included 25 papers conducted in 11 countries across three continents (North America, Asia and Europe). Summary odds ratios (ORs) for highest versus non/lowest tea consumption levels were calculated based on fixed and random effects models. The meta-regression and stratified methods were used to examine heterogeneity across studies. For green tea, the combined results from eight studies indicated a reduced risk of colorectal cancer with intake [summary OR = 0.82, 95% confidence interval (CI) = 0.69-0.98]. The protective effect is mainly found among the three case-control studies of colon cancer (summary OR = 0.74, 95% CI = 0.60-0.93). Results from studies of rectal cancer irrespective of study design (case-control versus cohort) (summary OR = 0.99, 95% CI = 0.71-1.37) and cohort studies of colon cancer (summary OR = 0.99, 95% CI = 0.79-1.24) were compatible with the null hypothesis. For black tea, the summary OR derived from 20 studies was 0.99 (95% CI = 0.87-1.13). There is wide divergence in results across the 20 individual studies; formal tests for homogeneity across studies revealed statistically significant differences in findings across all studies (P < 0.001), amongst the 7 cohort studies (P = 0.002), and amongst the 13 case-control studies (P < 0.001). Despite the strong evidence from in vitro and non-human in vivo studies in support of green and black tea as potential chemopreventive agents against colorectal cancer, available epidemiologic data are insufficient to conclude that either tea type may protect against colorectal cancer in humans.

Adenocarcinoma↗

PubMed2006

Prediagnostic level of serum retinol in relation to reduced risk of hepatocellular carcinoma.

BACKGROUND: Retinol and its derivatives (retinoids), which have antioxidant activity and promote cell differentiation, may protect against the development of hepatocellular carcinoma (HCC) by controlling hepatocellular differentiation and reducing inflammatory responses. METHODS: We examined prospectively the relationship between prediagnostic serum concentrations of retinol, alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; and selenium and the risk of developing HCC among 213 patients with HCC and 1087 matched control subjects from a cohort of 18,244 men in Shanghai, China, who were monitored from 1986 through 2001. Odds ratios (ORs) and 95% confidence intervals (CIs) for men by quartile of serum concentrations of micronutrients were estimated by using logistic regression with adjustment for cigarette smoking status, alcohol intake, self-reported history of physician-diagnosed hepatitis or liver cirrhosis at recruitment, and seropositivity for hepatitis B surface antigen (HBsAg). All statistical tests were two-sided. RESULTS: Men with high prediagnostic serum retinol levels had a lower risk of HCC than men in the lowest quartile (Q2 versus Q1, OR = 0.37, 95% CI = 0.22 to 0.61; Q3 versus Q1, OR = 0.30, 95% CI = 0.17 to 0.50; and Q4 versus Q1, OR = 0.13, 95% CI = 0.06 to 0.26; Ptrend < .001). A statistically significant interaction was observed between retinol and HBsAg seropositivity on HCC risk; HBsAg-positive men in the lowest tertile of retinol had a greater than 70-fold higher risk (OR = 72.7, 95% CI = 31.6 to 167.4) of HCC than HBsAg-negative men in the highest tertile of retinol (Pinteraction = .018). No independent effect of serum levels of alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; or selenium on HCC risk were observed. CONCLUSION: High prediagnostic serum level of retinol is associated with a decreased risk of HCC in this population.

Carcinoma, Hepatocellular↗

PubMed2006

Peroxisome proliferator-activated receptor (PPAR) gamma gene polymorphisms and colorectal cancer risk among Chinese in Singapore.

Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-activated nuclear receptor that plays a key role in adipogenesis and adipocyte gene expression, and has recently been linked with possible antineoplastic effects in colonic carcinogenesis. PPARgamma2 and gamma3 are two transcripts arising from the PPARgamma gene through differential promoter usage and alternative splicing. We investigated the associations between PPARgamma2 Pro12Ala and PPARgamma3 C-681G gene polymorphisms and colorectal cancer (CRC) risk in a case-control study nested within the Singapore Chinese Health Study. Genotypes for the PPARgamma2 and PPARgamma3 polymorphisms were determined on 362 incident CRC cases and 1164 cohort controls by direct sequencing and by fluorogenic 5'-nuclease assay. Unconditional logistic regression models were used for statistical analyses. With adjustment for CRC risk factors, subjects with one or two copies of the G allele of the PPARgamma2 Pro12Ala polymorphism showed a statistically significant reduction in risk compared to those with the CC genotype [odds ratio (OR)=0.53, 95% confidence interval (CI)=0.30-0.92]. For the PPARgamma3 C-681G polymorphism, subjects with one or two copies of the C allele showed a reduction in risk compared to those with the GG genotype (OR=0.72, 95% CI=0.51-1.04). When PPARgamma2 and PPARgamma3 genotypes were considered simultaneously, the number of putative low-risk genotypes was significantly associated with reduced risk of CRC in a gene-dose-dependent manner; the OR (95% CI) was 0.72 (0.49-1.07) among subjects possessing one low-risk genotype (either PPARgamma2 or PPARgamma3), and the comparable figure among subjects possessing both low-risk genotypes was 0.19 (0.07-0.51).

Aged↗

PubMed2006

Diabetes mellitus and risk of colorectal cancer in the Singapore Chinese Health Study.

The incidence of colorectal cancer is highest in populations that consume an energy-dense diet, have low intakes of vegetables and fruit, or lead a sedentary lifestyle. These factors may influence colorectal carcinogenesis via insulin pathways. We examined whether diabetes mellitus was associated with colorectal cancer in Singapore Chinese, whose body type and lifestyle profiles are distinct from those of Western populations. Between April 1993 and December 1998, 63,257 Singapore Chinese men and women aged 45 to 74 years were enrolled in a prospective study of diet and cancer. Each subject provided dietary, medical, and lifestyle information through an in-person interview. As of December 31, 2002, 636 incident colorectal cancer cases had been diagnosed. A history of physician-diagnosed diabetes was statistically significantly associated with colorectal cancer risk in both men (relative risk [RR] = 1.5, 95% confidence interval [CI] = 1.2 to 2.1) and women (RR = 1.4, 95% CI = 1.0 to 1.9). In stratified analyses, this association remained statistically significant among the subset of diabetics with high total calorie intake and low physical activity levels. Our results support the hypothesis that hyperinsulinemia may play a role in colorectal carcinogenesis, even in a relatively lean population.

Aged↗

PubMed2006

In situ encapsulation of horseradish peroxidase in electrospun porous silica fibers for potential biosensor applications.

Nanoporous silica nanofibers have been employed as a matrix to encapsulate horseradish peroxide enzymes via a simple electrospinning method. A viscous solution of prehydrolyzed tetramethyl orthosilicate, beta-d-glucose, poly(vinyl alcohol), and enzymes were employed as spinning solution to generate porous fibers in the form of nonwoven mats. The silica fiber mats thus produced have a high surface area because of the small diameter (100 to 200 nm) of the fibers as well as the extreme porosity (2 to 4 nm) of individual fibers caused by the glucose template present in them. The high surface area, mechanical flexibility, thermal stability, reusability, and freedom of encapsulating various enzymes make porous silica nanofibers excellent biosensors.

Biosensing Techniques↗

PubMed2005

Green tea, black tea and breast cancer risk: a meta-analysis of epidemiological studies.

Experimental studies have shown that tea and tea polyphenols have anti-carcinogenic properties against breast cancer. A number of epidemiologic studies, both case-control and cohort in design, have examined the possible association between tea intake and breast cancer development in humans. This meta-analysis included 13 papers which examined populations in eight countries and provided data on consumption of either green tea or black tea, or both in relation to breast cancer risk. Summary odds ratios (ORs) for highest versus non/lowest tea consumption level were calculated based on fixed and random effects models. Heterogeneity between studies was examined via the Q statistics. For green tea, the combined results from the four studies indicated a reduced risk of breast cancer for highest versus non/lowest intake (OR = 0.78, 95% CI = 0.61-0.98). For black tea, conflicting results were observed in case-control versus cohort studies. The combined results from the eight case-control studies showed a minor inverse association between black tea consumption and risk of breast cancer (OR = 0.91, 95% CI = 0.84-0.98). This inverse association was stronger in hospital-based (OR = 0.77, 95% CI = 0.50-1.19) than population-based case-control studies (OR = 0.94, 95% CI = 0.81-1.09). Five cohort studies demonstrated a modest increase in risk associated with black tea intake (OR = 1.15, 95% CI = 1.02-1.31). The results of this meta-analysis indicate a lower risk for breast cancer with green tea consumption. Available data suggest a possible late-stage, promotional effect of black tea on breast carcinogenesis.

Animals↗

PubMed2005

Green tea intake, ACE gene polymorphism and breast cancer risk among Chinese women in Singapore.

Experimental and epidemiological data have implicated a potential chemoprotective role of green tea polyphenols and a potential enhancing role of angiotensin II in the development of breast cancer in humans. Angiotensin II is converted from its precursor by angiotensin-converting enzyme (ACE). Women with low-activity genotype of the ACE gene had a reduced risk of breast cancer compared with those possessing high-activity ACE genotype. Experimental data showed that green tea polyphenols could inhibit angiotensin II-induced reactive oxygen species production. We reasoned that if this is one of the mechanisms by which green tea polyphenols protect against human breast cancer, then their effect should be more prominent among women possessing high-activity ACE genotype than women with low-activity ACE genotype. In other words, we predict a stronger inverse green tea-breast cancer association among the former versus the latter subgroup of women. To test this hypothesis, we conducted a nested case-control study involving 297 incident breast cancer cases and 665 control subjects within the Singapore Chinese Health Study. There was no association between intake frequencies of green tea and risk of breast cancer among all women or those with low-activity ACE genotype. Among women with high-activity ACE genotype, however, intake frequency of green tea was associated with a statistically significant decrease in risk of breast cancer (P for trend=0.039); the odds ratio (95% confidence interval) was 0.33 (0.13-0.82) for women drinking green tea at least monthly and 0.29 (0.10-0.79) for those drinking green tea at least weekly compared with non-drinkers. There was a statistically significant interaction effect between green tea intake and ACE genotype on risk of breast cancer (P for interaction=0.01). Black tea intake was unrelated to breast cancer risk irrespective of the ACE genotype. The findings of the present study highlight the importance of genetically determined factors in evaluating the role of green tea intake in the development of breast cancer.

Adult↗

PubMed2005

Effect of cytokine genotypes on the hepatitis B virus-hepatocellular carcinoma association.

BACKGROUND: In Southern Guangxi, China, chronic infection with the hepatitis B virus (HBV) acquired during the perinatal period from carrier mothers is a primary cause of hepatocellular carcinoma. However, only a minority of HBV carriers eventually develop hepatocellular carcinoma. The authors hypothesized that cytokine genotypes may be important codeterminants of the risk of HBV-related hepatocellular carcinoma. METHODS: The authors examined the correlation between polymorphisms in T-helper 1 (Th1) and Th2 cytokine genes among a group of 250 patients with incident hepatocellular carcinoma (cases) and a group of 250 hospital controls who were matched individually to the index case by age, gender, ethnicity, residence, and month of hospital admission in the city of Nanning, Guangxi, China. RESULTS: Relative to the putative high-activity genotypes, each individual low-activity genotype of interferon gamma, interleukin 12 (IL12), and IL18 was associated with a statistically nonsignificant increase (40-60%) in the risk of hepatocellular carcinoma. This risk increased with increasing numbers of low-activity Th1 genotypes after adjusting for potential confounders (2-sided P value for trend=0.04). Conversely, individual Th2 (IL4, IL10) low-activity genotypes were associated with a statistically nonsignificant reduced risk of hepatocellular carcinoma. This risk decreased with increasing number of low-activity Th2 genotypes after adjusting for potential confounders (2-sided P value for trend=0.01). Individuals who had the maximum number (i.e., 3) of low-activity Th1 genes and the minimum number (i.e., 0) of low-activity Th2 genes showed a relative risk of 20.0 (95% confidence interval, 1.7-235.0). CONCLUSIONS: Diminished cell-mediated immune response, which is controlled genetically, appeared to be an important risk determinant of HBV-related hepatocellular carcinogenesis.

Adult↗

PubMed2005

A pilot study of an alcoholic liver disease recurrence prevention education program in hospitalized patients with advanced liver disease.

No systematic work has been completed to assess whether or not educational programming might exert lifestyle improvements among alcoholic liver disease (ALD) inpatients. The present pilot study sought to answer this question through the use of a small-scale two-group experiment (five-session education program versus standard care) at a state-of-the art Liver Unit that provided tertiary care of indigent patients with advanced ALD. A total of 44 patients were initially randomly assigned to program conditions, and 25 provided 3-month follow-up data (13 in the program condition, 12 in the control condition). Patients who received the program reported high receptivity to it, and showed greater learning of program material and reported greater lifestyle changes than the control patients. For those ALD inpatients that are able and willing to participate, the program shows promising effects on self-reported lifestyle change.

Adult↗

PubMed2005

Middle-aged and older Chinese men and women in Singapore who smoke have less healthy diets and lifestyles than nonsmokers.

Although studies in Western populations have shown that smokers have decreased dietary intakes of antioxidants and other health-related nutrients, this has not been established in oriental populations. This study aimed to identify differences in dietary and lifestyle characteristics between current, former, and never-smokers among middle-aged and older Chinese in Singapore. The subjects, 45-74 y old, were participants in the Singapore Chinese Health Study, a prospective cohort that enrolled 63,257 (27,959 men and 35,298 women) Chinese in Singapore between 1993 and 1998. Data on current dietary habits (using a validated, semiquantitative FFQ) and other lifestyle factors were collected through face-to-face interviews. Mean daily intakes of various nutrients were estimated using a food composition table that was specifically developed for this population. The current smoking rates were 36% in men and 6% in women; an additional 22% of men and 3% of women were former smokers. In both sexes, current smokers were less educated, had lower BMI, led a more sedentary lifestyle, and drank more alcohol and coffee than those who never smoked. Current smokers had dose-dependent decreases in the intakes of a wide range of antioxidants, vitamins, fiber, and calcium, but increases in the intakes of cholesterol and nitrosamines compared with people who never smoked. Former smokers had dietary intakes that either were similar to never-smokers or intermediate between current and never-smokers. Our results are consistent with findings among Western populations, and suggest that the unhealthy diet and lifestyle in smokers occur across diverse cultures.

Aged↗

PubMed2004

Dietary soy and increased risk of bladder cancer: a prospective cohort study of men in Shanghai, China.

To verify our previous finding of a positive association between dietary soy and bladder cancer risk, we examined the association in a second, geographically distinct prospective cohort of Chinese subjects, the Shanghai Cohort Study. Briefly, 18,244 men aged 45-64 years were recruited between January 1986 and September 1989. As of December 31, 2002, 61 incident bladder cancer cases were identified. Information on soy consumption was obtained through in-person interviews at baseline using a food frequency questionnaire. Cox proportional hazard regression methods were used to estimate relative risks (RR) and their corresponding 95% confidence intervals (CI), with adjustment for age (years) at baseline interview, level of education and other potential confounders. Compared to men consuming soy less than once a week, the RR (95% CI) for those who consumed soy 1-<3 times per week, 3-<7 times a week and daily were 2.05 (0.80-5.29), 2.45 (0.89-6.76) and 4.61 (1.57-13.51), respectively (p for trend = 0.004), after adjustment for age, cigarette smoking and level of education. The soy-bladder cancer risk associations in smokers and non-smokers were comparable. The soy-bladder cancer relationship became stronger when the analysis was restricted to subjects with 2 or more years of follow-up.

China↗

PubMed2004

Polymorphisms in angiotensin II type 1 receptor and angiotensin I-converting enzyme genes and breast cancer risk among Chinese women in Singapore.

Angiotensin II is converted from its precursor by angiotensin I-converting enzyme (ACE) and has been shown to mediate growth in breast cancer cell lines via ligand-induced activity through the angiotensin II type 1 receptor (AGTR1). Earlier we showed that women with the low activity genotype of the ACE gene have a statistically significantly ( approximately 50%) reduced breast cancer risk compared with those possessing the high activity ACE genotype. To further test the hypothesis that angiotensin II participates in breast carcinogenesis through AGTR1, we examined genetic polymorphisms in the 5'-region of the AGTR1 gene (A-168G, C-535T and T-825A) in relation to risk of breast cancer in 258 breast cancer cases and 670 female controls within the Singapore Chinese Health Study. Relative to the homozygotes, individual genotypes with one or two copies of the respective allelic variants (putative low risk genotypes) were each associated with an approximately 30% reduction in risk of breast cancer. Risk of breast cancer decreased with increasing number of low risk AGTR1 genotypes after adjustment for potential confounders. Relative to those carrying no low risk genotypes (homozygous for A, C and T alleles for the three polymorphisms, respectively), the odds ratios (95% confidence intervals) were 0.84 (0.51-1.37) for women possessing one low risk genotype and 0.68 (0.46-1.01) for women possessing two or three low risk genotypes (P for trend = 0.05). When both AGTR1 and ACE gene polymorphisms were examined simultaneously, women possessing at least one AGTR1 low risk genotype in combination with the ACE low activity genotype had an odds ratio of 0.35 (95% confidence interval, 0.20-0.62) compared with those possessing the ACE high activity genotype and no AGTR1 low risk genotype. Our findings suggest that pharmacological inhibition of the angiotensin II effect by blockade of ACE and/or AGTR1 could be potential targets for the prevention and treatment of breast cancer.

Aged↗

PubMed2004

Reversible mechanical unfolding of single ubiquitin molecules.

Single-molecule manipulation techniques have enabled the characterization of the unfolding and refolding process of individual protein molecules, using mechanical forces to initiate the unfolding transition. Experimental and computational results following this approach have shed new light on the mechanisms of the mechanical functions of proteins involved in several cellular processes, as well as revealed new information on the protein folding/unfolding free-energy landscapes. To investigate how protein molecules of different folds respond to a stretching force, and to elucidate the effects of solution conditions on the mechanical stability of a protein, we synthesized polymers of the protein ubiquitin and characterized the force-induced unfolding and refolding of individual ubiquitin molecules using an atomic-force-microscope-based single-molecule manipulation technique. The ubiquitin molecule was highly resistant to a stretching force, and the mechanical unfolding process was reversible. A model calculation based on the hydrogen-bonding pattern in the native structure was performed to explain the origin of this high mechanical stability. Furthermore, pH effects were studied and it was found that the forces required to unfold the protein remained constant within a pH range around the neutral value, and forces decreased as the solution pH was lowered to more acidic values.

Computer Simulation↗

PubMed2004

Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S.

BACKGROUND: Heavy alcohol consumption, viral hepatitis, and diabetes are risk factors for hepatocellular carcinoma (HCC). However, to the authors' knowledge, the information concerning their interaction effect in patients with risk of HCC is sparse. METHODS: A population-based, case-control study of HCC was conducted during 1984-2002. The study involved 295 HCC cases and 435 age-, gender-, and race-matched control subjects among Hispanic and non-Hispanic whites and blacks in Los Angeles County, California. Lifestyle risk factors were ascertained through in-person interviews. Infections with the hepatitis B and C (HCV) viruses were determined using their serologic markers. RESULTS: Fourteen HCC cases but no control subjects tested positive for the hepatitis B surface antigen. Seropositivity for antibodies to HCV was associated with an odds ratio (OR) of 125 (95% confidence interval [95% CI], 17-909) for HCC, whereas seropositivity for antibodies to the hepatitis B core antigen was related to an OR of 2.9 (95% CI, 1.7-5.0). Heavy alcohol consumption and cigarette smoking were found to be independently associated with a statistically significant two to threefold increase in risk of HCC after adjustment for hepatitis B and C serology. Subjects with a history of diabetes had an OR of 2.7 (95% CI, 1.6-4.3) for HCC compared with nondiabetic subjects. A synergistic interaction on HCC risk was observed between heavy alcohol consumption and diabetes (OR = 4.2; 95% CI, 2.6-5.8), heavy alcohol consumption and viral hepatitis (OR = 5.5; 95% CI, 3.9-7.0), or between diabetes and viral hepatitis (OR = 4.8; 95% CI, 2.7-6.9). CONCLUSIONS: Heavy alcohol consumption, diabetes, and viral hepatitis were found to exert independent and synergistic effects on risk of HCC in U.S. blacks and whites.

Adolescent↗

PubMed2004

Carotenoids/vitamin C and smoking-related bladder cancer.

Previous epidemiological studies of fruit and vegetable intake and bladder cancer risk have yielded inconsistent results, especially with respect to the role of cigarette smoking as a possible modifier of the diet-bladder cancer association. A population-based case-control study was conducted in nonAsians of Los Angeles, California, which included 1,592 bladder cancer patients and an equal number of neighborhood controls matched to the index cases by sex, date of birth (within 5 years) and race between January 1, 1987 and April 30, 1996. Information on smoking, medical and medication history, and intake frequencies of food groups rich in preformed nitrosamines, vitamins A and C and various carotenoids, were collected through in-person, structured interviews. Beginning in January 1992, all case patients and their matched control subjects were asked for a blood sample donation at the end of the in-person interviews for measurements of 3- and 4-aminobiphenyl (ABP) hemoglobin adducts, and glutathione S-transferases M1/T1/P1 (GSTM1/T1/P1) and N-acetyltransferase-1 (NAT1) genotypes. Seven hundred seventy-one (74%) case patients and 775 (79%) control subjects consented to the blood donation requests. In addition, all case patients and matched control subjects were asked to donate an overnight urine specimen following caffeine consumption for measurements of cytochrome P4501A2 (CYP1A2) and N-acetyltransferase-2 (NAT2) phenotypes. Urine specimens were collected from 724 (69%) case patients and 689 (70%) control subjects. After adjustment for nondietary risk factors including cigarette smoking, there were strong inverse associations between bladder cancer risk and intake of dark-green vegetables [p value for linear trend (p) = 0.01], yellow-orange vegetables (p = 0.01), citrus fruits/juices (p = 0.002) and tomato products (p = 0.03). In terms of nutrients, bladder cancer risk was inversely associated with intake of both total carotenoids (p = 0.004) and vitamin C (p = 0.02). There was a close correlation (r = 0.58, p = 0.0001) between intakes of total carotenoids and vitamin C in study subjects. When both nutrients were included in a multivariate logistic regression model, only total carotenoids exhibited a residual effect that was of borderline statistical significance (p = 0.07 and p = 0.40 for total carotenoids and vitamin C, respectively). Cigarette smoking was a strong modifier of the observed dietary effects; these protective effects were confined largely to ever smokers and were stronger in current than ex-smokers. Smokers showed a statistically significant or borderline statistically significant decrease in 3- and 4-aminobiphenyl (ABP)-hemoglobin adduct level with increasing intake of carotenoids (p = 0.04 and 0.05, respectively). The protective effect of carotenoids on bladder cancer seemed to be influenced by NAT1 genotype, NAT2 phenotype and CYP1A2 phenotype; the association was mainly confined to subjects possessing the putative NAT1-rapid, NAT2-rapid and CYP1A2-rapid genotype/phenotype. The carotenoid-bladder cancer association was not affected by the GSTM1, GSTT1 and GSTP1 genotypes.

Acyltransferases↗

PubMed2004

Environmental factors and risk for hepatocellular carcinoma.

Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most important risk factors for the development of hepatocellular carcinoma (HCC) in humans. HBV is the primary cause of HCC in high-risk areas including China and Africa, whereas in developed countries such as the United States, HCV plays a more prominent role and is at least partially responsible for the increase in HCC incidence in this country. Humans are exposed to hepatocarcinogenic aflatoxins through ingestion of moldy foods, a consequence of poor storage of susceptible grains. Highly exposed populations are primarily in sub-Sahara Africa and Asia, where dietary aflatoxins significantly enhance the carcinogenic effects of viral hepatitis. Heavy, long-term alcohol use is a risk factor for HCC, whereas moderate use (1-3 drinks/day) is not. Constituents of cigarette smoke are hepatic carcinogens in animals, and there is mounting evidence that the liver is an organ susceptible to tobacco carcinogenicity. Diabetic patients are at risk for HCC probably as a result of the hepatic injury, fibrosis, and eventual cirrhosis resulting from fatty liver disease. Given the current epidemic of obesity and diabetes in the United States, this risk factor will be increasingly important. Increased risk for HCC is evident in young noncirrhotic users of oral contraceptives in the United States and Europe. In summary, risk factors for HCC are identifiable in most patients and primarily are associated with chronic hepatic injury.

Aflatoxins↗