Biomedical subjects

Mimi C Yu

Publications and source records attributed to Mimi C Yu.

At least 37 records · Page 2Linked to original sources

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

Tea and circulating estrogen levels in postmenopausal Chinese women in Singapore.

The role of tea in the etiology of breast cancer is controversial. We recently provided the first set of human evidence that breast cancer risk is significantly inversely associated with tea intake, largely confined to intake of green tea. Since black tea and green tea possess comparable levels of the total tea polyphenols that possess antioxidative activities, reasons for the paradoxical effects of green tea and black tea on breast cancer protection are not apparent. Some limited evidence suggests that green tea may have downregulatory effects on circulating sex-steroid hormones, whereas black tea may have upregulatory effects. We therefore, investigated the relationship between tea intake, and plasma estrogen and androstenedione levels in a cross-sectional study of healthy postmenopausal Chinese women in Singapore. In this group of 130 women, 84 were non or irregular (less than once a week) tea drinkers, 27 were regular (weekly/daily) green tea drinkers and 19 were regular (weekly/daily) black tea drinkers. Relative to plasma estrone levels in non- or irregular tea drinkers (29.5 pg/ml) the levels were 13% lower in regular green tea drinkers (25.8 pg/ml) and 19% higher in regular black tea drinkers (35.0 pg/ml). These differences in estrone levels were statistically significant (P = 0.03) inspite of adjusting for age, body mass index, intake of soy, and other covariates. A similar pattern of differences between tea intake, and plasma levels of estradiol (P = 0.08) and androstenedione (P = 0.14) were found. In addition, the tea-estrogen associations were observed irrespective of the genotype of catechol-O-methyltransferase (COMT), a major enzyme that aids in the excretion of tea polyphenols in humans. Larger studies are needed to confirm results from this cross-sectional study and to better understand the potentially differing effect of black and green tea on circulating estrogen levels and ultimately on the risk of breast cancer.

Aged↗

PubMed2005

Increased hepatocarcinogenic potential of hepatitis B virus genotype A in Bantu-speaking sub-saharan Africans.

Genotypes A, D, and E of the hepatitis B virus (HBV) circulate in southern Africa, with genotype A predominating. Their hepatocarcinogenic potential in Bantu-speaking sub-saharan Africans is, however, unknown. Using a case/control format, we investigated the hepatocarcinogenic potential of these genotypes and subgenotype A1 of genotype A, which accounts for the great majority of genotype A isolates. HBV isolates from 111 unselected Bantu-speaking sub-saharan Africans with hepatocellular carcinoma (HCC) and 111 matched asymptomatic chronic carriers, serving as controls, were genotyped using the method of [Lindh et al. (1997): J Infect Dis 175:1285-1293]. Subgenotypes of genotype A were determined using an in-house restriction fragment length polymorphism assay. Genotype A was present in 96 (86.5%) of patients with HCC and 76 (68.5%) of the carriers, giving a 4.5-fold (95% confidence limits: 1.86, 10.90) increased risk of HCC in carriers infected with genotype A compared with those infected with non-A genotypes. HCC patients infected with genotype A were significantly younger than those infected with non-A genotypes (P = 0.02). The distributions between these two groups according to sex, geographic background, and tribe were not significantly different. Subgenotype A1 was present in all of the 77 cancer patients and 69 of 70 carriers analyzed, yielding a relative risk of 4.21 (95% confidence limits: 1.73,10.23) of HCC in those infected with subgenotype A1 compared with those infected with non-A genotypes. Genotype A has a greater hepatocarcinogenic potential than non-A genotypes in Bantu-speaking sub-saharan Africans and this is entirely attributable to subgenotype A1.

Adolescent↗

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↗

PubMed2005

249ser p53 mutation in the serum of black southern African patients with hepatocellular carcinoma.

BACKGROUND AND AIMS: A specific mutation at codon 249 of the p53 tumor suppressor gene (guanine to thymine; arginine to serine [249(serine)p53]) is present in the cell-free plasma of 30-47% of patients with hepatocellular carcinoma (HCC) in regions with uniformly high levels of dietary exposure to the fungal toxin, aflatoxin B(1). No information is available from other regions. We therefore examined cell-free serum from HCC patients in southern Africa, where aflatoxin B(1) exposure ranges from very high to low levels. METHODS: DNA extracted from the serum of 158 black African patients with HCC was amplified by the polymerase chain reaction assay using primers specific for exon 7 of the p53 gene, and submitted to endonuclease cleavage with HaeIII to identify the 249(serine)p53 mutation. The presence of the mutation was confirmed by nucleotide sequencing. RESULTS: The specific mutation was detected in 18% of the patients, giving an odds ratio for HCC in those with the mutation of 13.3 (95% confidence limits 1.8; 100.2). Surprisingly, the mutation was present equally often in rural and urban patients, despite presumed levels of aflatoxin B(1) exposure in the latter being much lower. No correlation was found with the presence of hepatitis B virus infection or the age, sex or tribe of the patients. CONCLUSIONS: The 249(serine)p53 mutation is found less often in the serum of patients with HCC in a region with variable levels of exposure to aflatoxin B(1) than in those with uniformly high levels of exposure, but the mutation does occur in black Africans with presumed lower levels of exposure to the fungal toxin.

Adolescent↗

PubMed2005

Comparison of prostate-specific antigen and hormone levels among men in Singapore and the United States.

Prostate cancer incidence rates markedly vary between countries. The highest rates of prostate cancer are observed in Western countries such as the United States, whereas the lowest rates are seen in Asian countries such as Singapore. To gain an understanding of the difference in prostate cancer burden between low-risk and high-risk populations, we examined serum prostate-specific antigen (PSA) levels among Singapore-Chinese men (n = 315) from the Singapore Chinese Health Study and African-American (n = 440), U.S. White (n = 355), U.S. Latino (n = 523), and Japanese-American (n = 349) men from the Hawaii-Los Angeles Multiethnic Cohort Study. All men had no history of prostate cancer at the time of blood draw. PSA measurements were assayed by one centralized diagnostic facility. Testosterone and 3alpha-androstanediol glucuronide levels were examined in a subsample of men. Scheffe's multiple comparison tests were used to evaluate differences in PSA and hormone levels between groups. PSA levels among the Singapore-Chinese (geometric mean = 1.43 ng/mL) were similar to that of African-Americans (1.46 ng/mL), U.S. Whites (1.28 ng/mL), and Japanese-Americans (1.22 ng/mL) and significantly higher than U.S. Latinos (1.18 ng/mL; P = 0.038). Although there was a strong correlation (R2= 0.89) between PSA levels and U.S. ethnic group-specific prostate cancer incidence rates before PSA screening (1983-1987), the levels among the Singapore-Chinese completely failed to relate to their low incidence rate. Testosterone and 3alpha-androstanediol glucuronide levels did not reflect racial/ethnic patterns of disease. Our results highlight a potentially large group of Singapore-Chinese men with undiagnosed prostate cancer. Given that the overall mortality rate of prostate cancer in Singapore is low, these undiagnosed cancers may be of nonaggressive type. Alternatively, PSA may be a poor marker of prostate cancer in this low-risk population.

Age Distribution↗

PubMed2005

A new single nucleotide polymorphism in the insulin-like growth factor I regulatory region associates with colorectal cancer risk in singapore chinese.

Elevated levels of plasma insulin-like growth factor I (IGF-I) are a potential risk factor for several cancers, including colorectal cancer. Physiologic levels of plasma IGF-I vary greatly; this variation may be in part genetically determined. We identified two single nucleotide polymorphisms (SNP) in perfect linkage disequilibrium with each other and in partial linkage disequilibrium with a previously studied cytosine-adenine microsatellite [-969(CA)(n)]. We investigated one of the SNPs, -533T/C,and the 969(CA)(n) in relation to the risk of colorectal cancer in a case-control study nested within a cohort of Singapore Chinese (cases/controls = 290:873). The (CA)(21) allele, rather than the previously implicated (CA)(19) allele, was associated with a reduced risk of colorectal cancer (odds ratio for 21/21 versus all other genotypes, 0.48; 95% confidence interval, 0.28-0.84). For the -533C/T SNP, persons carrying one or more copies of the C allele had a decreased in risk of colorectal cancer compared with noncarriers (odds ratio for CC/CT versus TT, 0.58; 95% confidence interval, 0.41-0.82). This association was specific for colon, as opposed to rectal cancer and was modified by age. We also examined a functional insulin-like growth factor binding protein (IGFBP3) promoter SNP, -202 A/C, previously reported to predict serum IGFBP3 levels. Although we were able to confirm this genotype-phenotype association, the -202A/C IGFBP3 SNP was not significantly associated with colorectal cancer risk. In conclusion, we report a novel SNP in the IGF-I regulatory region that is associated with colorectal cancer risk.

Alleles↗

PubMed2004

DNA hypomethylation is prevalent even in low-grade breast cancers.

Hypomethylation of some portions of the genome and hypermethylation of others are very frequent attributes of human cancer. We previously showed that cancer-associated DNA hypomethylation often involves satellite 2 (Sat2), the main DNA component of the large juxtacentromeric (centromere-adjacent) heterochromatin of chromosome 1. In this study, we compared methylation of Sat2 and centromeric satellite DNA (Satalpha) as well as overall genomic methylation in 41 breast adenocarcinomas of known tumor grade and stage, 16 non-neoplastic breast tissues (mostly fibroadenomas), and a variety of normal somatic tissue controls. The cancers were significantly hypomethylated at Sat2 relative to the fibroadenomas or normal somatic tissues and at Satalpha relative to the normal somatic tissues. However, unlike Sat2, Satalpha did not display significant differences in methylation between the cancers and the non-neoplastic breast tissues. Therefore, hypomethylation at Sat2 is a much better marker of breast cancer than is Satalpha hypomethylation. There was a significant association of Sat2 hypomethylation with global DNA hypomethylation in the cancers but not with tumor grade, stage, axillary lymph node involvement, or hormone receptor status. Extensive cancer-associated hypomethylation of juxtacentromeric satellite DNA and global DNA hypomethylation were common even in grade-1 or stage-1 carcinomas, which suggests that demethylation of the genome is an early event in breast carcinogenesis.

Adult↗

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

Alkylaniline-hemoglobin adducts and risk of non-smoking-related bladder cancer.

BACKGROUND: Some members of the arylamine family of compounds, specifically 4-aminobiphenyl (ABP), 2-naphthylamine, and benzidine, are established human bladder carcinogens. Cigarette smoking and use of permanent hair dye contribute substantially to current arylamine exposure. Low levels of 4-ABP exposure have been associated with non-smoking-related bladder cancer. Other arylamine compounds coming from as yet unidentified environmental sources may also be human bladder carcinogens. METHODS: We conducted a population-based case-control study in Los Angeles County, California, involving 298 case subjects with bladder cancer and 308 control subjects, who were matched on age, sex, race/ethnicity, and neighborhood of residence. In-person interviews provided information on tobacco smoking and other potential risk factors for bladder cancer. To assess arylamine exposure, levels of arylamine-hemoglobin adducts of nine selected alkylanilines (2,3-dimethylaniline [2,3-DMA], 2,4-DMA, 2,5-DMA, 2,6-DMA, 3,4-DMA, 3,5-DMA, 2-ethylaniline [2-EA], 3-EA, 4-EA) were measured in peripheral blood collected from study subjects. Analysis of covariance and conditional logistic regression methods were used to analyze the relationship between arylamine-hemoglobin adducts and bladder cancer risk. All statistical tests were two-sided. RESULTS: Levels of all arylamine-hemoglobin adducts, with the exception of 2,6-DMA, were higher in smokers than in nonsmokers, and levels of all arylamine-hemoglobin adducts were higher in case subjects than in control subjects. Arylamine-hemoglobin adducts of 2,6-DMA, 3,5-DMA, and 3-EA were all independently, statistically significantly (all P<.001) associated with bladder cancer risk after adjusting for cigarette smoking at the time of blood collection, lifetime smoking history, and other potential risk factors. These adducts were also independently associated with bladder cancer risk when only nonsmokers at time of blood draw were considered (highest quartile versus lowest quartile: 2,6-DMA, relative risk [RR] of bladder cancer = 8.1, 95% confidence interval [CI] = 3.6 to 18.0; 3,5-DMA, RR = 2.7, 95% CI = 1.2 to 6.0; 3-EA, RR = 4.3, 95% CI = 1.6 to 11.6). CONCLUSIONS: Diverse arylamine exposures are strongly associated with bladder cancer risk among nonsmokers. Because arylamines may account for a substantial proportion of bladder cancers among the general population, identification of environmental sources of these compounds is needed.

Aminobiphenyl Compounds↗

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

Marine n-3 fatty acid intake, glutathione S-transferase polymorphisms and breast cancer risk in post-menopausal Chinese women in Singapore.

We have previously found marine n-3 fatty acids to be inversely related to post-menopausal breast cancer in Chinese women from Singapore. Post-menopausal women with high [quartiles 2-4 (Q2-Q4)] versus low [quartile 1 (Q1)] intake exhibited a statistically significant reduction in risk of breast cancer after adjustment for potential confounders [relative risk (RR) = 0.66, 95% confidence interval (CI) = 0.50, 0.87]. Experimental studies have demonstrated a direct role for the peroxidation products of marine n-3 fatty acids in breast cancer protection. There is a suggestion that the glutathione S-transferases (GSTs) may be major catalysts in the elimination of these beneficial by-products. Therefore, we hypothesized that individuals possessing the low activity genotypes of GSTM1, GSTT1 and/or GSTP1 (i.e. the GSTM1 null, GSTT1 null and GSTP1 AB/BB genotypes, respectively) may exhibit a stronger marine n-3 fatty acid-breast cancer association than their high activity counterparts. The Singapore Chinese Health Study is a prospective investigation involving 35,298 middle-aged and older women, who were enrolled between April 1993 and December 1998. In this case-control analysis, nested within the Singapore Chinese Health Study, we compared 258 incident breast cancer cases with 670 cohort controls. Overall, breast cancer risk was unrelated to GSTM1 and GSTP1 genotypes. However, the GSTT1 null genotype was associated with a 30% reduced risk of breast cancer [odds ratio (OR) = 0.71, 95% CI = 0.52, 0.96]. Among women with high activity GST genotypes (i.e. GSTM1 positive, GSTT1 positive and GSTP1 AA), no marine n-3 fatty acid-breast cancer relationships were observed in either pre-menopausal or post-menopausal women at baseline. However, post-menopausal women possessing the combined GSTM1 null and GSTP1 AB/BB genotypes showed a statistically significant reduction in risk after adjustment for potential confounders (Q2-Q4 versus Q1, OR = 0.36, 95% CI = 0.14, 0.94). A similar relationship was observed among women with the combined GSTT1 null and GSTP1 AB/BB genotypes (OR = 0.26, 95% CI = 0.08, 0.78).

Aged↗

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

Association of metabolic gene polymorphisms with tobacco consumption in healthy controls.

Polymorphisms in genes that encode for metabolic enzymes have been associated with variations in enzyme activity between individuals. Such variations could be associated with differences in individual exposure to carcinogens that are metabolized by these genes. In this study, we examine the association between polymorphisms in several metabolic genes and the consumption of tobacco in a large sample of healthy individuals. The database of the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens was used. All the individuals who were controls from the case-control studies included in the data set with information on smoking habits and on genetic polymorphisms were selected (n = 20938). Sufficient information was available on the following genes that are involved in the metabolism of tobacco smoke constituents: CYP1A1, GSTM1, GSTT1, NAT2 and GSTP1. None of the tested genes was clearly associated with smoking behavior. Information on smoking dose, available for a subset of subjects, showed no effect of metabolic gene polymorphisms on the amount of smoking. No association between polymorphisms in the genes studied and tobacco consumption was observed; therefore, no effect of these genes on smoking behavior should be expected.

Arylamine N-Acetyltransferase↗

PubMed2004

Dietary fiber and reduced cough with phlegm: a cohort study in Singapore.

Smoking is the major risk factor for chronic respiratory symptoms, but dietary factors may also play a role. Most studies of diet and lung disease have been cross-sectional and conducted in populations with a Western-style diet. We analyzed the relation between dietary intake at baseline and new onset of cough with phlegm in a population-based cohort of 63,257 middle-aged Chinese men and women initiated in Singapore between 1993 and 1998. Beginning in 1999, we ascertained respiratory symptoms by telephone interview and have identified 571 incident cases of cough with phlegm among the 49,140 cohort members with completed follow-up. Nonstarch polysaccharides, a major component of dietary fiber, total fruit, and soy isoflavones had the strongest associations. Odds ratios comparing highest and lowest quartiles after adjustment for age, sex, dialect group, total energy intake, and smoking were 0.61 (95% confidence interval [CI]: 0.47, 0.78; p for trend < 0.001) for nonstarch polysaccharides, 0.67 (95% CI: 0.52, 0.87; p for trend = 0.006) for fruit, and 0.67 (95% CI: 0.53, 0.86; p for trend = 0.001) for soy isoflavones. These data suggest that a diet high in fiber from fruit and, possibly, soyfoods may reduce the incidence of chronic respiratory symptoms. Associated nutrients, such as flavonoids, may contribute to this association.

Age Distribution↗

PubMed2004

Detection of residual subclinical ovarian carcinoma after completion of adjuvant chemotherapy.

PURPOSE: We sought to test the hypothesis that the presence of telomerase activity in peritoneal washings of patients treated for ovarian carcinoma is a sensitive and specific indicator of the presence of residual disease. We hypothesized that this test, if added to second-look procedure protocols, could help determine whether residual disease is present or not in patients who have completed their adjuvant chemotherapy for ovarian carcinoma. EXPERIMENTAL DESIGN: Peritoneal washings were obtained from 100 consecutive patients undergoing a second-look procedure after treatment for ovarian carcinoma (cases) and from 100 patients undergoing surgery for benign gynecological conditions (controls). The washings were assayed for telomerase activity using the telomerase repeat amplification protocol. The results were compared to the histological and cytological findings. RESULTS: Among our 100 cases, 82 (82%) had either positive second-look procedures or expressed telomerase in their peritoneal washings. Fifty-three (53%) had positive second-look procedures, whereas 66 (66%) tested positive for telomerase. Twenty-nine of the 47 patients (62%) with negative second-look procedures tested positive for telomerase. Of the 53 patients with positive second-look procedures, 37 (70%) tested positive for telomerase. None of the 100 controls (0%) expressed telomerase in their peritoneal washings. CONCLUSIONS: Telomerase activity in peritoneal washings of patients treated for ovarian carcinoma and undergoing a second-look procedure may provide a means of increasing the sensitivity of such procedures for the detection of residual disease while maintaining a high level of specificity.

Adult↗