Sex steroid hormones and genetic susceptibility to breast and prostate cancer.
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Animals↗
Biomedical subjects
M C Yu
Publications and source records attributed to M C Yu.
Screening of human immunodeficiency virus infection in pulmonary tuberculosis patients in Taiwan.
To disclose the impact of human immunodeficiency virus (HIV) infection on the tuberculosis epidemic in Taiwan, we prospectively screened for HIV infection in patients with active pulmonary tuberculosis. A total of 378 patients who were admitted to the Taiwan Provincial Chronic Disease Control Bureau from January through December 1996 were enrolled. HIV serologic testing was performed by enzyme-linked immunosorbent assay (ELISA). A positive ELISA test was confirmed by Western blot analysis. One patient was infected with HIV. We conclude that the impact of HIV infection on the epidemic of tuberculosis in Taiwan is not significant at present.
Adolescent↗
A urinary biomarker for uptake of dietary isothiocyanates in humans.
Isothiocyanates (ITCs) are a family of biologically active compounds that are distributed widely in cruciferous vegetables. Although studies in rodents have shown that these compounds are effective and versatile inhibitors of tumorigenesis, the role of dietary ITCs in the protection against human cancers remains to be established. A prerequisite of human studies is to develop an uptake biomarker for dietary ITCs. In this study, we describe a rapid high-performance liquid chromatography-based assay to measure the total ITC level in human urine. This assay is based on a previously described reaction of ITCs or their thiol conjugates with 1,2-benzenedithiol to yield a cyclocondensation product, 1,3-benzodithiole-2-thione, which then can be quantified by reverse phase high-performance liquid chromatography with UV detection. This new assay was validated by analyzing urine samples from 14 subjects who had consumed a known amount of watercress or brown mustard in a controlled experiment. The N-acetylcysteine conjugates of phenethyl ITC and allyl ITC from watercress and brown mustard, respectively, were quantified and compared with the results obtained from the current assay. Results of the two methods were highly correlated (r = 0.978), indicating the specificity of this new assay for dietary ITCs. The feasibility of this assay for population-based studies was examined using stored urine samples collected from nine participants of a prospective cohort study in Shanghai, China, who indicated that they were daily consumers of dark green vegetables. There was a 10-fold variation in urinary ITC contents among these samples, ranging from 0.7 to 7.0 micromol/g creatinine. These results show the potential use of this uptake biomarker in epidemiological studies to identify the role of dietary ITCs in modifying cancer risks in humans.
Anticarcinogenic Agents↗
Isoflavonoid levels in spot urine are associated with frequency of dietary soy intake in a population-based sample of middle-aged and older Chinese in Singapore.
Soy products contain high amounts of isoflavonoids, which have been shown to exhibit possible cancer-protective properties. Chinese populations in Asia, in particular, have a high level of soy intake and a relatively low risk of hormone-dependent cancers. In this study, we assessed the distributions of dietary soy isoflavonoids (daidzein, genistein, and glycitein) and urinary soy isoflavonoids and their metabolites (daidzein, genistein, glycitein, equol, and O-desmethylangolensin) among 147 Singapore Chinese (76 men and 71 women) ages 45-74 years, who are participants of the Singapore Cohort Study on diet and cancer. Urinary values were measured from spot samples collected 10-20 months following recruitment, when usual dietary habits were assessed by a structured food frequency/portion size questionnaire administered in person. Dietary levels of daidzein and genistein were comparable within individuals and about seven times higher than the level of dietary glycitein. All three dietary isoflavonoids showed an approximately 3.5-fold difference between the 25th and 75th percentile values. Similarly, daidzein was the most abundant and glycitein the least abundant of the five isoflavonoid compounds in urine. There was a 4.9-fold difference between the 25th and 75th percentile values for the sum of the five urinary isoflavonoids. Among study subjects, there were statistically significant, dose-dependent associations between frequency of overall soy intake and levels of urinary daidzein (two-sided P = 0.03) and sum of urinary daidzein, genistein, and glycitein (two-sided P = 0.04). In contrast, there were no associations between frequency of overall soy intake and levels of the two daidzein metabolites (equol and O-desmethylangolensin) in urine (two-sided P = 0.85 and 0.34, respectively). We suggest that within the range of exposures experienced by Singapore Chinese, urinary level of daidzein or the sum of daidzein, genistein, and glycitein obtained from a spot sample can serve as a biomarker of current soy consumption in epidemiological studies of diet-disease associations.
Aged↗
Short-course chemotherapy for isoniazid-resistant pulmonary tuberculosis.
Standard short-course chemotherapy including isoniazid, rifampicin, pyrazinamide, and ethambutol has been the recommended treatment for tuberculosis in Taiwan since November 1990. The effectiveness of this treatment was evaluated retrospectively in 108 patients with isolates resistant to isoniazid alone and 115 patients with drug-susceptible pulmonary tuberculosis diagnosed and treated at the Taiwan Provincial Chronic Disease Control Bureau from November 1990 through December 1995. The success rate of treatment was 94.4% in patients with isoniazid-resistant Mycobacterium tuberculosis strains, which was not significantly different from the 97.4% rate in patients with susceptible strains. Of the patients treated successfully, no bacteriologic relapse was found in 97 patients with isoniazid-resistant strains or 103 patients with drug-susceptible strains 12 months after the end of chemotherapy. No significant advantage in treatment outcome was found in patients infected with isoniazid-resistant strains who received chemotherapy for more than 6 months (successful treatment rate, 95.0% vs 92.8%), but the failure rate was higher in patients with a previous history of antituberculosis therapy (17.6% vs 3.3%). We conclude that short-course chemotherapy is effective for isoniazid-resistant pulmonary tuberculosis and that there is no significant difference in treatment outcome between patients with or without isoniazid-resistant disease.
Antitubercular Agents↗
Tobacco use in relation to renal cell carcinoma.
The modest effect of cigarette smoking on renal cell carcinoma (RCC) requires a study with a large number of subjects to definitively answer the question of whether smoking is causally related to RCC. A population-based case-control study was conducted in Los Angeles, California that involved 1204 RCC patients and an equal number of neighborhood controls who were matched to the index cases by sex, date of birth (within 5 years), and race. Detailed information on tobacco use was collected through in-person interviews. Cigarette smoking was associated with a statistically significant 35% increase in the risk of RCC [odds ratio (OR), 1.35; 95% confidence interval (CI), 1.14-1.60]. The risk increased with increasing number of cigarettes smoked per day (two-sided P < 0.001, linear trend test). Former smokers (OR, 1.24; 95% CI, 1.02-1.50) had a lower risk of RCC than current smokers (OR, 1.53; 95% CI, 1.23-1.90). Compared with current smokers, those who quit smoking 10 or more years ago experienced a statistically significant 30% reduction in the risk of RCC. Current smokers who smoked 40 or more cigarettes/day experienced a nearly 2-fold increase in the risk of RCC compared with lifelong nonsmokers. The association between cigarette smoking and RCC was similar in men and women. There were no measurable differences in the risk of RCC between filtered and nonfiltered cigarette smokers or between those who inhaled cigarette smoke deeply and those who inhaled lightly after adjustment for the number of cigarettes smoked per day and current smoking status. After the effect of cigarette smoking was accounted for, heavy cigar smokers (14 or more cigars/week) exhibited a statistically significant 70% increase in the risk of RCC, but no increased risk of RCC was observed for the use of pipes or smokeless tobacco. Seventeen percent of RCC (21% in men and 11% in women) in Los Angeles, California can be attributed to cigarette smoking.
Adult↗
Absence of the glutathione S-transferase M1 gene increases cytochrome P4501A2 activity among frequent consumers of cruciferous vegetables in a Caucasian population.
The cancer protective effect of cruciferous vegetables has been attributed to induction of phase II enzymes. But cruciferous vegetables also induce cytochrome P4501A2 (CYP1A2), which catalyzes the metabolic activation of various procarcinogens, including aromatic amines in tobacco. Thus, frequent intake of cruciferous vegetables could also result in cancer-enhancing effects. GSTM1 is involved in the detoxification of various carcinogens, but it also enhances the excretion of isothiocyanates and possibly other enzyme inducers in cruciferous vegetables. We, therefore, hypothesized that GSTM1 null genotype might be associated with increased CYP1A2 activity among frequent consumers of cruciferous vegetables because the excretion of CYP1A2 inducers contained in these vegetables may be partially inhibited in the absence of the GSTM1 enzyme. Three hundred twenty-eight non-Hispanic white residents of Los Angeles County (265 males and 63 females) were genotyped for the presence or absence of GSTM1 alleles and phenotyped for CYP1A2 activity. Information on usual dietary habits was obtained from these subjects through in-person interviews. Among frequent (at least once a week) consumers of broccoli, GSTM1 null individuals exhibited a 21% higher geometric mean level of CYP1A2 activity relative to GSTM1 non-null individuals (5.24 versus 4.32, two-sided P = 0.01). No such difference was observed in subjects who consumed broccoli less frequently (two-sided P = 0.39). This interactive effect of GSTM1 genotype and vegetable intake on CYP1A2 activity also was observed when overall intake of the five cruciferous vegetables under study (broccoli, cabbage, cauliflower, Brussels sprouts, and mustard greens) was examined. Among weekly consumers of cruciferous vegetables, GSTM1 null individuals showed a 16% higher geometric mean level of CYP1A2 activity relative to GSTM1 non-null individuals (5.03 versus 4.33, two-sided P = 0.02), whereas no difference was evident among those who consumed cruciferous vegetables less frequently (two-sided P = 0.35). Our results suggest that cruciferous vegetables contain CYP1A2 inducers, which are deactivated in the presence of GSTM1.
Brassicaceae↗
Ethambutol-induced pulmonary infiltrates with fever and skin rash: a case report.
A 55-year-old man presented with the suspicion of pulmonary tuberculosis. He was treated with isoniazid, ethambutol, rifampicin and pyrazinamide. However, he developed high fever, skin rash and pulmonary infiltrates following 10 days of treatment. The above-mentioned conditions subsided promptly after stopping ethambutol therapy and reappeared after rechallenge, marking ethambutol as the offender. To present knowledge, this is the second case of an ethambutol-induced hypersensitivity lung reaction reported in English literature.
Antitubercular Agents↗
Drug resistance patterns of tuberculosis in Taiwan.
To evaluate the patterns of drug resistance of Mycobacterium tuberculosis in Taiwan, a total of 1,091 isolates collected from patients from January 1996 through December 1996 were tested for drug susceptibility using the absolute concentration method at the Taiwan Provincial Chronic Disease Control Bureau. The overall drug rate of resistance to at least one drug was 35.5%. Among the 249 isolates from patients who had never been treated for tuberculosis, 16.1% were resistant to one or more drugs; 1.6% were resistant to at least isoniazid and rifampin. Of 200 patients with prior antituberculosis treatment, 67.0% had isolates resistant to one or more drugs and 46.0% had isolates resistant to at least isoniazid and rifampin. We conclude that drug-resistant M. tuberculosis is an important issue in tuberculosis treatment in Taiwan, especially when dealing with patients with a prior history of antituberculosis treatment. More aggressive interventions, such as directly observed therapy, short-course, are needed to improve the cure rate of pulmonary tuberculosis and to decrease resistance rates.
Adolescent↗
Urinary total isothiocyanate (ITC) in a population-based sample of middle-aged and older Chinese in Singapore: relationship with dietary total ITC and glutathione S-transferase M1/T1/P1 genotypes.
Isothiocyanates (ITCs), degradation products of glucosinolates (which occur naturally in a variety of cruciferous vegetables), have been shown to exhibit chemopreventive activity. These compounds are metabolized in vivo to form the corresponding dithiocarbamates, which are the major urinary metabolites of ITCs, by a pathway involving the glutathione S-transferase (GST) class of enzymes. Using a newly developed assay that measures total ITC (primarily ITC conjugates) in urine, we examined the relationships between cruciferous vegetable intake (obtained from a food frequency/portion size questionnaire administered in person); dietary total ITC level; GSTM1, GSTT1, and GSTP1 genotypes; and levels of total ITC in spot urine samples collected from 246 Singapore Chinese (111 men and 135 women), ages 45-74 years, who are participants of the Singapore Cohort Study on diet and cancer. Consumption level of cruciferous vegetables was high in study subjects (mean consumption = 345 times per year, mean daily intake = 40.6 g), which was >3 times the comparable level of intake in the United States. Mean daily intake of total ITC among study subjects was 9.1 micromol, and there was a 2.5-fold difference between the 25th and 75th percentile values. Seventy-three % of study subjects tested positive for ITC in urine, and there was a 4-fold difference between the 25th and 75th percentile values among the positive subjects. There was a highly significant positive association between dietary intake and urinary excretion levels of total ITC (two-sided P = 0.0003) that was stronger than the association between overall cruciferous vegetable intake and urinary ITC level, which also was statistically significant (P = 0.0004). There was no difference in urinary ITC levels between GSTM1-null and GSTM1-positive study subjects (P = 0.61) or between subjects with differing GSTP1 genotypes (P = 0.77), but urinary excretion of ITC was significantly higher among GSTT1-positive subjects, relative to GSTT1-null subjects (P = 0.006). The strength of the association between GSTT1 genotype and urinary total ITC level was highly dependent on the level of cruciferous vegetable consumption (or dietary ITC level) in study subjects. Among subjects in the lowest tertile of cruciferous vegetable intake, there was little evidence of an association between GSTT1 genotype and urinary total ITC level (P = 0.67). In contrast, there was a strong and statistically significant association between GSTT1 genotype and urinary total ITC among subjects in the highest tertile of cruciferous vegetable intake (P = 0.02), whereas those in the middle tertile of cruciferous vegetable consumption exhibited an association of intermediate strength (P = 0.04). These results suggest the presence of GSTT1 inducers in cruciferous vegetables.
Age Factors↗
Genetic variation of 3 beta-hydroxysteroid dehydrogenase type II in three racial/ethnic groups: implications for prostate cancer risk.
BACKGROUND: Elevated prostatic dihydrotestosterone (DHT) has been suggested to increase the risk of prostate cancer. The HSD3B2 gene encodes the type II 3 beta-hydroxysteroid dehydrogenase: one of two enzymes that initiate the inactivation of DHT. Thus, the HSD3B2 gene is a candidate gene for predisposition to prostate cancer. METHODS: We have determine the distribution of a complex dinucleotide repeat in the HSD3B2 gene in high-risk African-Americans, intermediate-risk Euro-Americans, and low-risk Asians. Genomic DNA from 312 individuals was amplified by polymerase chain reaction (PCR) and analyzed by electrophoresis on denaturing polyacrylamide gels. RESULTS: We have found that certain alleles are either unique to or much more common in either African-Americans, Asians, or Euro-Americans. Our data also substantially expand the number of alleles reported for the complex dinucleotide repeat polymorphism in the HSD3B2 gene. CONCLUSIONS: Our report demonstrates substantial genetic variation in the HSD3B2 gene. We hypothesize that allelic variants of the HSD3B2 gene may play a role in predisposition to prostate cancer, and in explaining the substantial racial/ethnic variation in risk.
3-Hydroxysteroid Dehydrogenases↗
Prospective evaluation of dietary and other predictors of fatal stroke in Shanghai, China.
BACKGROUND: Although a number of risk factors for fatal stroke are well established in Western populations, this is less true for Asian countries, many of which have stroke mortality rates that are historically high. In a prospective study in Shanghai, China, we determined whether the same factors predict risk for fatal stroke as in the West. We also studied a number of potential dietary associations, particularly those with dietary antioxidants because these have been suggested to reduce atherogenesis. METHODS AND RESULTS: Between 1986 and 1989, 18 244 men aged 45 to 64 years living in four geographically defined areas of Shanghai, China were recruited to participate in a prospective study of diet and cancer. All participants completed an in-person, structured interview and provided blood and urine samples. As of March 1994, fatal stroke accounted for 245 of the 980 observed deaths. The most important risk factor for stroke mortality was a history of hypertension (multivariate relative risk, 4.5; 95% confidence interval, 3.3, 6.2). Cigarette smoking was not strongly associated with risk, and alcohol consumption increased risk only in the extreme categories of lifetime consumption. Educational level was strongly, inversely associated with fatal stroke, and this could not be explained by adjustment for any other risk factors. No macronutrient was associated with risk, including total energy, fat consumption, or any component of fat. There also were no significant inverse associations for stroke mortality with several micronutrients of interest, including vitamin C, carotene, vitamin E, riboflavin, or calcium. CONCLUSIONS: Our data demonstrate that hypertension is by far the most important contributor to stroke mortality in Shanghai and that among dietary factors, only alcohol consumption shows any evidence whatsoever of being a risk factor.
Alcohol Drinking↗
An explanation for the increasing incidence of testis cancer: decreasing age at first full-term pregnancy.
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Adult↗
A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase.
Prostate cancer is the most common serious cancer diagnosed in men in the United States. This disease is also characterized by a striking racial/ethnic variation in incidence: highest in African-Americans, intermediate in Caucasians, slightly lower in Latinos, and lowest in Asians. Ample biochemical and epidemiological evidence suggests a role for androgens, particularly testosterone and dihydrotestosterone, in prostate cancer etiology. We have analyzed a candidate gene for prostate cancer, SRD5A2, encoding prostatic steroid 5alpha-reductase type II, which converts testosterone into the more bioactive dihydrotestosterone, for mutations. We report here one amino acid substitution, V89L, which replaces valine at codon 89 with leucine. This substitution is a "germline" (constitutional) DNA polymorphism, and it is common, panethnic, and reduces in vivo steroid 5alpha-reductase activity. This substitution is particularly common among Asians and may explain the low risk for prostate cancer in this population.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
Smoking, alcohol use, dietary factors and risk of small intestinal adenocarcinoma.
To investigate the role of tobacco and alcohol use and dietary factors in the etiology of small intestinal adenocarcinoma, we analyzed data from a large population-based case-control study of multi-site cancers conducted in Los Angeles County between 1975 and 1984. The present analysis included interview information on 36 small intestinal adenocarcinoma patients and 998 population controls. After adjusting for age and ethnicity, men who smoked more than 100 cigarettes during their lifetimes were at a non-significantly 3-fold increased risk for small intestinal adenocarcinoma; this association was substantially weaker in women. In men and women combined, a significant 3-fold increased risk in heavy drinkers (80+ g ethanol/day) relative to more moderate drinkers and non-drinkers was observed. Although frequent (>6 times vs. less than 2 times of intake a week) intake of foods rich in heterocyclic aromatic amines (based on the combined intake of fried bacon and ham, barbecued and/or smoked meat and smoked fish) was associated with a significant 4.5-fold increased risk of small intestinal adenocarcinoma in men; this association was not present in women. Based on 2 questions that provided a crude assessment of sugar intake, risk of small intestinal adenocarcinoma in men and women appeared to be associated with adding sugar regularly in coffee or tea and daily intake of non-diet carbonated soft drinks. When we computed total sugar intake from tea, coffee and non-diet carbonated soft drinks, there was a consistent and significant trend of increasing sugar intake and risk of small intestinal adenocarcinomas. Compared with the lowest intake level a day (<5 g), medium (5-25 g) and high intakes (>25 g) were associated with ORs of 2.5 and 3.8, respectively.
Adenocarcinoma↗
Possible relation between hypertension and cancers of the renal pelvis and ureter.
To evaluate the relationship of selected medical conditions and medications with cancers of the renal pelvis and ureter, we interviewed 308 subjects with renal pelvis cancer, 194 subjects with ureter cancer and 496 control subjects in 3 areas of the United States. After controlling for the effects of smoking, age, gender and geographic residence, a history of hypertension (reported to have been diagnosed more than 5 years before interview) was associated with a small but significantly increased risk (odds ratio [OR] = 1.3; 95% confidence interval [CI], 1.0-1.8), whereas no relationship was observed with a variety of other medical conditions or medications. Stratified analysis showed that the risk associated with hypertension was twice as high among users of diuretics or other antihypertensive drugs (OR = 2.4; 95% CI, 1.1-4.9) as it was among those who never used these medications (OR = 1.2; 95% CI, 0.8-1.7). Our findings suggest that the association previously reported between hypertension and renal cell cancer may extend to cancers of the renal pelvis and ureter.
Adult↗
Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor.
BACKGROUND: Prostate cancer is an increasingly common disease for which there are few well-established risk factors. Family history data suggest a genetic component; however, the majority of prostate cancer cases cannot be explained by a single-gene model. Prostate cell division is influenced by two steroid hormones, testosterone and vitamin D, the action of each being mediated by its respective receptor. The genes for the two receptors are candidates in a multigenic model for prostate cancer susceptibility. PURPOSE: We examined genetic polymorphisms in two steroid receptors, the androgen receptor (AR) and the vitamin D receptor (VDR), in a case-control pilot study of prostate cancer. METHODS: Fifty-seven non-Hispanic white case patients with prostate cancer and 169 non-Hispanic white control subjects were genotyped for a previously described microsatellite (CAG repeats) in the AR gene and for a newly discovered poly-A microsatellite in the 3'-untranslated region (3'UTR) of the VDR gene. To compare genotypes with respect to prostate cancer risk, we estimated odds ratios (ORs) by using logistic regression. ORs were also estimated separately for advanced and localized cases of disease. All P values resulted from two-sided tests. RESULTS: Both the AR and the VDR polymorphisms were associated, individually and after mutual adjustment, with prostate cancer. Adjusted ORs (95% confidence intervals [CIs]) for prostate cancer were 2.10 (95% CI = 1.11-3.99) for individuals carrying an AR CAG allele with fewer than 20 repeats versus an allele with 20 or more repeats and 4.61 (95% CI = 1.34-15.82) for individuals carrying at least one long (A18 to A22) VDR poly-A allele versus two short (A14 to A17) poly-A alleles. For both the AR and VDR genes, the at-risk genotypes were more strongly associated with advanced disease than with localized disease. CONCLUSIONS: In this pilot study, genetic variation in both the VDR and the AR genes was associated with prostate cancer, and both genes appear to preferentially confer risk for advanced disease. These two genetic risk factors, if confirmed, are among the strongest risk factors yet identified for prostate cancer. IMPLICATIONS: These results are consistent with a multigenic model of prostate cancer susceptibility. On the basis of the joint effect of several genetic loci, one might ultimately be able to construct a risk profile to predict advanced disease, so that men whose disease is unlikely to progress to an advanced stage can possibly be spared aggressive treatment.
Alleles↗
Follow up study of moderate alcohol intake and mortality among middle aged men in Shanghai, China.
OBJECTIVE: To assess the risk of death associated with various patterns of alcohol intake. DESIGN: Prospective study of mortality in relation to alcohol consumption at recruitment, with active annual follow up. SETTING: Four small, geographically defined communities in Shanghai, China. SUBJECTS: 18,244 men aged 45-64 years enrolled in a prospective study of diet and cancer during January 1986 to September 1989. MAIN OUTCOME MEASURE: All cause mortality. RESULTS: By 28 February 1995, 1198 deaths (including 498 from cancer, 269 from stroke, and 104 from ischaemic heart disease) had been identified. Compared with lifelong non-drinkers, those who consumed 1-14 drinks a week had a 19% reduction in overall mortality (relative risk 0.81; 95% confidence interval 0.70 to 0.94) after age, level of education, and cigarette smoking were adjusted for. This protective effect was not restricted to any specific type of alcoholic drink. Although light to moderate drinking (28 or fewer drinks per week) was associated with a 36% reduction in death from ischaemic heart disease (0.64; 0.41 to 0.998), it had no effect on death from stroke, which is the leading cause of death in this population. As expected, heavy drinking (29 or more drinks per week) was significantly associated with increased risks of death from cancer of the upper aerodigestive tract, hepatic cirrhosis, and stroke. CONCLUSIONS: Regular consumption of small amounts of alcohol is associated with lower overall mortality including death from ischaemic heart disease in middle aged Chinese men. The type of alcoholic drink does not affect this association.
Alcohol Drinking↗