Biomedical subjects

Mimi C Yu

Publications and source records attributed to Mimi C Yu.

70 records · Page 4Linked to original sources

PubMed2002

Arylamine exposures and bladder cancer risk.

Occupational exposure to arylamines in industrial settings was the first known cause of bladder cancer in humans. In the United States and many developed countries, these industrial dyes have been under strict government control for decades and are believed to contribute minimally to today's population burden of bladder cancer in the West. The two other recognized, and potentially substantial sources of human exposure to arylamines are cigarette smoking and use of hair dyes. This paper reviews the latest epidemiologic findings on the relationships between smoking, hair dye use and bladder cancer risk. Results support the notion that arylamines contained in cigarette smoke and permanent hair dyes are human carcinogens. Furthermore, women may experience higher bladder cancer risk than men from comparable arylamine exposure, possibly due in part to women's higher propensity for arylamine activation relative to men.

Amines↗

PubMed2002

Hypomethylation and hypermethylation of DNA in Wilms tumors.

We quantitatively analysed hypermethylation at CpG islands in the 5' ends of 12 genes and one non-CpG island 5' region (MTHFR) in 31 Wilms tumors. We also determined their global genomic 5-methylcytosine content. Compared with various normal postnatal tissues, approximately 40-90% of these pediatric kidney cancers were hypermethylated in four of the genes, MCJ, RASSF1A, TNFRSF12 and CALCA as determined by a quantitative bisulfite-based assay (MethyLight). Interestingly, the non-CpG island 5' region of MTHFR was less methylated in most tumors relative to the normal tissues. By chromatographic analysis of DNA digested to deoxynucleosides, about 60% of the Wilms tumors were found to be deficient in their overall levels of DNA methylation. We also analysed expression of the three known functional DNA methyltransferase genes. No relationship was observed between global genomic 5-methylcytosine levels and relative amounts of RNA for DNA methyltransferases DNMT1, DNMT3A, and DNMT3B. Importantly, no association was seen between CpG island hypermethylation and global DNA hypomethylation in these cancers. Therefore, the overall genomic hypomethylation frequently observed in cancers is probably not just a response or a prelude to hypermethylation elsewhere in the genome. This suggests that the DNA hypomethylation contributes independently to oncogenesis or tumor progression.

CpG Islands↗

PubMed2002

Thymidylate synthase: a novel genetic determinant of plasma homocysteine and folate levels.

The thymidylate synthase gene ( TYMS or TS) encodes a tightly regulated enzyme that catalyzes the conversion of deoxyuridylate to thymidylate, and contains a tandem repeat polymorphism that affects expression of the enzyme. We have investigated the relationship between TYMS genotype and plasma concentrations of homocysteine and folate in a cohort of 505 Chinese from Singapore. TYMS 3/3 genotype was associated with reduced plasma folate and, among individuals with low dietary folate intake, with elevated plasma homocysteine levels. These associations were independent of the well-established methylenetetrahydrofolate reductase ( MTHFR) C677T genotype effects on plasma folate and homocysteine levels. Our results suggest that TYMS and MTHFR compete for limiting supplies of folate required for the remethylation of homocysteine. These genetic determinants of plasma folate and homocysteine levels may be useful in identifying individuals at increased risk for cardiovascular disease.

Cohort Studies↗

PubMed2002

Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer.

BACKGROUND: Members of the glutathione S-transferase (GST) superfamily are important in cellular defense mechanisms. These enzymes attach reduced glutathione to electrophilic groups in a wide variety of toxic compounds, including chemotherapeutic agents. Certain polymorphisms in GSTs are associated with changes in enzyme activity, sensitivity to chemotherapy, and overall patient survival. In a retrospective study, we investigated associations between common polymorphisms in genes for several GST subclasses (GSTP1, GSTT1, GSTM1) and survival of patients with metastatic colorectal cancer receiving 5-fluorouracil (5-FU)/oxaliplatin chemotherapy. METHODS: During 1998-2000, 107 previously treated patients with advanced colorectal cancer received 5-FU/oxaliplatin combination chemotherapy. Associations between deletion polymorphisms in GSTM1 and GSTT1 genes and between a polymorphism in the GSTP1 gene that generates an Ile(105)Val in the GSTP1 protein and survival were evaluated using relative risks (RRs) of dying and the log-rank test. All statistical tests were two-sided. RESULTS: Patients heterozygous for the GSTP1 polymorphism had an RR = 0.47 (95% confidence interval [CI] = 0.27 to 0.81) compared with patients homozygous for the GSTP1 (105)Ile allele. Patients homozygous for the mutant polymorphism had an RR = 0.16 (95% CI = 0.04 to 0.63). After adjustment for performance status and tumor site, the stratified RRs were 0.28 (95% CI = 0.07 to 1.10) for patients with two (105)Val alleles and 0.64 (95% CI = 0.36 to 1.16) for those with one (105)Val allele (P =.042). Patients with the (105)Val/(105)Val genotype survived a median of 24.9 months, those with the (105)Ile/(105)Ile genotype a median of 7.9 months, and those with the (105)Ile/(105)Val genotype a median of 13.3 months (P<.001). The GSTM1 and GSTT1 genotypes were not associated with survival or clinical response. CONCLUSIONS: The GSTP1 Ile(105)Val polymorphism is associated in a dose-dependent fashion with increased survival of patients with advanced colorectal cancer receiving 5-FU/oxaliplatin chemotherapy.

Adult↗

PubMed2002

Insulin-like growth factor I, IGF-binding protein 3, and lung cancer risk in a prospective study of men in China.

BACKGROUND: Insulin-like growth factor I (IGF-I) stimulates cell proliferation and inhibits apoptosis in the lung and other tissues by interacting with the IGF-I receptor. The major binding protein for IGF-I, insulin-like growth factor-binding protein 3 (IGFBP-3), modulates the effects of IGF-I but also inhibits cell growth and induces apoptosis independent of IGF-I and its receptor. In a prospective study of men in Shanghai, China, we examined the association between serum levels of IGF-I and IGFBP-3 and the subsequent risk of lung cancer. METHODS: From 1986 to 1989, serum was collected from 18,244 men aged 45-64 years living in Shanghai without a history of cancer. We analyzed IGF-I and IGFBP-3 levels in serum from 230 case patients who developed incident lung cancer during follow-up and from 740 control subjects. RESULTS: Among 230 case patients and 659 matched control subjects, increased IGF-I levels were not associated with increased risk of lung cancer. However, for subjects in the highest quartile relative to the lowest quartile of IGFBP-3, the odds ratio (OR) for lung cancer, adjusted for smoking and IGF-I, was 0.50 (95% confidence interval [CI] = 0.25 to 1.02). When the analysis was restricted to ever smokers (184 case patients and 344 matched control subjects), the OR for lung cancer in men in the highest quartile of IGFBP-3 relative to those in the lowest quartile, adjusted for smoking and IGF-I, was 0.41 (95% CI = 0.18 to 0.92). CONCLUSIONS: In this prospective study of Chinese men, higher serum levels of IGF-I did not increase the risk of lung cancer. However, subjects with higher serum levels of IGFBP-3 were at reduced risk of lung cancer. This finding is consistent with experimental data that indicate that IGFBP-3 can inhibit cellular proliferation and induce apoptosis independent of IGF-I and the IGF-I receptor.

Case-Control Studies↗

PubMed2002

Diet, reproductive factors and lung cancer risk among Chinese women in Singapore: evidence for a protective effect of soy in nonsmokers.

The factors associated with risk of lung cancer among nonsmokers have not been fully elucidated, but dietary factors have consistently been shown to play a role. Chinese women are unique in having a high incidence of lung cancer despite a low smoking prevalence. This population is also known to have a high intake of soy, a dietary source of phytoestrogens. We conducted a hospital-based case-control study among Singapore Chinese women, comprising 303 cases and 765 age-matched controls, of whom 176 cases and 663 controls were lifetime nonsmokers. Data on demographic background, reproductive factors and dietary intake of fruit, vegetables and soy foods were obtained by in-person interview. We observed an inverse association between intake of total, cruciferous and non-cruciferous vegetables and risk of lung cancer among smokers. Although smokers in the highest tertile of fruit intake also had a lower risk, this was not statistically significant. Higher intake of soy foods significantly reduced risk of lung cancer among lifetime nonsmokers, but not among smokers. When soy isoflavonoid intake in mg/week was computed based on frequency and portion size of intake of eight common local soy foods, the adjusted OR among nonsmokers for the highest tertile compared to the lowest was 0.56, 95% CI 0.37-0.85 (p for trend <0.01). Fruit intake was also significantly associated with reduced lung cancer risk among nonsmokers, but the effect was not significant after adjustment for soy intake. On the other hand, soy intake remained an independent predictor of risk after controlling for fruit intake. Reproductive effects were also primarily confined to lifetime nonsmokers, among whom having 3 or more livebirths (adjusted OR 0.65, 0.44-0.96) and a menstrual cycle length of more than 30 days (OR 0.46, 0.25-0.84) accorded a significantly reduced risk of lung cancer. Place of birth was significantly associated with risk among nonsmokers (OR 2.6, 1.7-3.9 for China-born vs. local born) but not among smokers. When analysis was restricted to nonsmokers with adenocarcinomas, the dietary effects were consistent or enhanced. On stepwise regression, soy intake and cycle length emerged as the independent dietary and reproductive predictors of lung cancer risk in nonsmokers. These findings are consistent with other evidence suggesting an involvement of estrogen-related pathways in lung cancer among non-smoking women.

Adult↗

PubMed2002

Epidemiology of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a rare malignancy in most parts of the world, with an incidence well under 1 per 100,000 person-years. Exceptions are the Chinese, especially the Cantonese living in the central region of Guangdong Province in Southern China. Other populations with elevated rates include the natives of Southeast Asia, the natives of the Artic region, and the Arabs of North Africa and parts of the Middle East. Intake of preserved foods at an early age has been linked to NPC risk in all population groups with increased NPC rates. Other recognized risk factors for NPC are cigarette smoking, and occupational exposure to formaldehyde and wood dust.

Age Distribution↗

PubMed2002

Lipid peroxidation: a novel and unifying concept of the etiology of renal cell carcinoma (United States).

Multiple studies have noted that obese individuals are at a high risk of renal cell cancer. Similarly, numerous case-control and cohort studies have consistently reported that individuals with a history of hypertension experience an increased risk of renal cancer. In spite of this compelling body of epidemiologic data, no credible hypothesis has been advanced to explain this dual etiologic association. In this communication we propose that lipid peroxidation, which is increased in obese and hypertensive subjects, is the mechanism responsible, at least in part. for their increased risk of renal cell carcinoma. In experimental animals lipid peroxidation of the proximal renal tubules is a necessary mechanistic pathway in renal carcinogenesis induced by several different chemicals. Our hypothesis may also explain the roles of other risk (oophorectomy/hysterectomy, parity, smoking, diabetes) and protective factors (dietary antioxidants) for renal cell cancer.

Age Distribution↗

PubMed2002

Dietary isothiocyanates, glutathione S-transferase polymorphisms and colorectal cancer risk in the Singapore Chinese Health Study.

Dietary intake of cruciferous vegetables (Brassica spp.) has been inversely related to colorectal cancer risk, and this has been attributed to their high content of glucosinolate degradation products such as isothiocyanates (ITCs). These compounds act as anticarcinogens by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). These enzymes also metabolize ITCs, such that the protective effect of cruciferous vegetables may predicate on GST genotype. The Singapore Chinese Health Study is a prospective investigation among 63 257 middle-aged men and women, who were enrolled between April 1993 and December 1998. In this nested case-control analysis, we compared 213 incident cases of colorectal cancer with 1194 controls. Information on dietary ITC intake from cruciferous vegetables, collected at recruitment via a semi-quantitative food frequency questionnaire, was combined with GSTM1, T1 and P1 genotype from peripheral blood lymphocytes or buccal mucosa. When categorized into high (greater than median) and low (less than/equal to median) intake, dietary ITC was slightly lower in cases than controls but the difference was not significant [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.59-1.12]. There were no overall associations between GSTM1, T1 or P1 genotypes and colorectal cancer risk. However, among individuals with both GSTM1 and T1 null genotypes, we observed a 57% reduction in risk among high versus low consumers of ITC (OR 0.43, 95% CI 0.20-0.96), in particular for colon cancer (OR 0.31, 0.12-0.84). Our results are compatible with the hypothesis that ITCs from cruciferous vegetables modify risk of colorectal cancer in individuals with low GST activity. Further, this gene-diet interaction may be important in studies evaluating the effect of risk-enhancing compounds in the colorectum.

Case-Control Studies↗

PubMed2002

Adolescent and adult soy intake and risk of breast cancer in Asian-Americans.

The association between soyfood intake and breast cancer risk is controversial. Most of the epidemiologic studies published on this topic in the 1990s were not designed to specifically address this question. We conducted a population-based, case-control study of breast cancer among Chinese, Japanese and Filipino women in Los Angeles County to further investigate the role of soy. Our primary objective was to quantify breast cancer risks associated with intake of soy during adolescence and adult life among Asian-American women. During 1995-1998, we successfully interviewed 501 breast cancer patients and 594 control subjects. Intake of soy among Asian-Americans is still relatively high; the median intake was 12 mg isoflavones/day, approximately one-third of that reported in a recent study in Shanghai, China. The risk of breast cancer was significantly inversely associated with soy intake during adolescence and adult life. After adjusting for age, specific Asian ethnicity, education, migration history and menstrual and reproductive factors, women who reported soy intake at least once per week during adolescence showed a statistically significantly reduced risk of breast cancer. There was also a significant trend of decreasing risk with increasing soy intake during adult life. When we considered soy intake during both adolescence and adult life, subjects who were high-soy consumers during both time periods showed the lowest risk (OR=0.53, 95% CI=0.36-0.78) compared with those who were low consumers during both time periods. Risk of breast cancer was intermediate among subjects who were high-soy consumers during adolescence and low-soy consumers during adult life (OR=0.77, 95% CI=0.51-1.10). Based on a relatively small number of subjects, the risk did not appear to differ between those who were low consumers during adolescence and high consumers during adult life. Results remained similar after adjustment for other potential confounders including other dietary and non-dietary risk factors for breast cancer. These results show that high soy intake in childhood in Asian-Americans is associated with reduced breast cancer risk. Risk may be further reduced by intake as an adult.

Asian↗

PubMed2002

Urinary tea polyphenols in relation to gastric and esophageal cancers: a prospective study of men in Shanghai, China.

Experimental studies have shown that tea and tea polyphenols have anticarcinogenic properties. There have been no prospective investigations examining the relationship between tea polyphenols and cancer risk using validated biomarkers. In the present study, a nested case-control study design was used to investigate the association between prediagnostic urinary tea polyphenol markers and subsequent risk of gastric and esophageal cancers. One hundred and ninety incident cases of gastric cancer and 42 cases of esophageal cancer occurring in members of the Shanghai Cohort (18 244 men aged 45-64 years at recruitment with up to 12 years of follow-up) were compared with 772 cohort control subjects. The control subjects were individually matched to the index cases by age, month and year of sample collection, and neighborhood of residence (case-control ratio = 1:3 for gastric cancer, 1:5 for esophageal cancer). Urinary tea polyphenols, including epigallocatechin (EGC) and epicatechin (EC), and their respective metabolites 5-(3',4',5'-trihydroxyphenyl)-gamma-valerolactone (M4) and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone (M6), were measured in all study subjects by means of a validated assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from logistic regression models. After exclusion of cases diagnosed under 4 years follow-up, urinary EGC positivity showed a statistically significant inverse association with gastric cancer (OR = 0.52, 95% CI = 0.28-0.97) after adjustment for Helicobactor pylori seropositivity, smoking, alcohol drinking, and level of serum carotenes. The protective effect was primarily seen among subjects with low (below population median) serum carotenes. The odds ratio for EGC positivity was 0.49 (95% CI = 0.26-0.94) among subjects with low serum carotenes while the corresponding odds ratio among subjects with higher levels of serum carotenes was 1.02 (95% CI = 0.46-2.28). Similar tea polyphenol-cancer risk associations were observed when the gastric cancer and esophageal cancer sites were combined. The present study provides direct evidence that tea polyphenols may act as chemopreventive agents against gastric and esophageal cancer development.

Adult↗

PubMed2002

A modified reduced-temperature antigen retrieval protocol effective for use with a polyclonal antibody to cyclooxygenase-2 (PG 27).

Antigen retrieval is now a standard procedure in immunohistochemical studies of tissues for diagnosis and research. While the most commonly used protocol (20 minutes at 100 degrees C in citrate buffer pH 6.0) is effective for many antibody/antigen combinations, experience has shown that in some instances, this standard approach fails. Under these circumstances, a successful antigen retrieval protocol may still be established by varying key conditions in the antigen retrieval process. The authors previously have advocated a test battery approach to determine the optimal conditions for antigen retrieval, illustrated here with respect to a polyclonal antibody to cyclooxygenase-2 (PG-27) that failed to give a positive staining result after orthodox antigen retrieval. The key feature of this modified antigen retrieval protocol is heating the deparaffinized tissue sections at a reduced temperature (90 degrees C as opposed to 100 degrees C). For this particular antibody, a boiling condition yields a negative result, a principal reason why previous investigators have used a tyramide signal amplification system to achieve satisfactory immunohistochemical results with this antibody. The optimal antigen retrieval protocol established in the authors' laboratory for this polyclonal antibody to cyclooxygenase-2 (PG-27) was evaluated in a study of formalin-fixed, paraffin-embedded cell lines and 31 bladder cancer tissue blocks using the tissue microarray technique, with side-by-side comparison between the results obtained by a tyramide signal amplification method (without antigen retrieval) and a standard immunohistochemical method with the optimized antigen retrieval protocol. The reduced temperature antigen retrieval protocol yielded a comparable or superior immunostaining for cyclooxygenase-2 both in cell lines and tissue blocks. In conclusion, use of the test battery approach allowed development of a modified antigen retrieval technique that provides a more reliable, much simpler approach for the demonstration of cyclooxygenase-2 in archival tissues.

Antibodies↗

PubMed2002

Mammographic parenchymal patterns and self-reported soy intake in Singapore Chinese women.

The study aimed to investigate whether self-reported dietary variables were associated with mammographic parenchymal patterns, which have been shown to predict risk of breast cancer. Among the 3,421 women, ages 45-74 years, common to two independent population-based cohorts, mammographic parenchymal patterns and current dietary habits were assessed for 406 randomly chosen participants. Logistic regression methods were used to compare dietary and other lifestyle profiles between subjects classified as displaying high (cases) and low risk (controls) parenchymal patterns. After adjustment for energy intake and other potential confounders, dietary soy protein intake was inversely related to risk of high-risk parenchymal pattern (odds ratio, 0.41; 95% confidence interval, 0.18-0.94, highest versus lowest quartile of intake). Similarly, the highest versus lowest quartile of dietary soy isoflavone intake was significantly related to low-risk parenchymal patterns (odds ratio, 0.44; 95% confidence interval, 0.20-0.98). The association between high soy intake and a reduced risk of mammographic parenchymal patterns that are associated with high breast cancer risk may have important implications in breast cancer prevention.

Age Distribution↗

PubMed2002

Soy intake and other lifestyle determinants of serum estrogen levels among postmenopausal Chinese women in Singapore.

Endogenous estrogen levels are strongly associated with breast cancer risk, but its determinants are not well understood. We conducted a cross-sectional study of 144 healthy postmenopausal women, participants in a population-based prospective investigation of diet and cancer risk among Chinese in Singapore. The relationships between plasma levels of estrone (E(1)), estradiol (E(2)), and androstenedione and dietary intake of soy and other food groups were investigated. Data on diet and other lifestyle factors were obtained from a structured questionnaire with a validated dietary component that was administered in-person to all participants. Few dietary factors emerged as determinants of plasma estrogen levels in this population. An exception was soy, which was significantly associated with plasma E(1) levels. Specifically, E(1) levels were 15% lower among individuals in the highest quartile of soy protein intake compared with those in the lower three quartiles of intake (P = 0.047). E(1) levels did not differ between individuals in the lower three quartiles of soy protein intake. Similar patterns of differences in E(1) levels emerged in analyses by intake of isoflavones and total soy products. These findings on soy were independent of the four nondietary factors (see below) that significantly influenced estrogen levels. Both E(1) and E(2) levels increased with high body mass index [BMI (weight/height(2))]; the respective levels were 41% (two-sided P = 0.02) and 17% higher (P = 0.34) among women in the highest BMI category (BMI >/= 24) compared with those in the lowest category (BMI < 20). After adjustment for BMI and age, women with a late age at menarche (age 17 years or older) showed significantly lower E(1) (30% lower; P = 0.02) and E(2) levels (24% lower; P = 0.02) compared with women with earlier age at menarche (before age 17 years) and who were nulliparous or had a late age at first live birth (after age 31 years). Current smokers showed significantly higher E(2) levels (28%) than nonsmokers (P = 0.04). These findings are discussed in relation to the recent doubling of breast cancer incidence among Chinese women in Singapore.

Aged↗

PubMed2002

Dietary soy and increased risk of bladder cancer: the Singapore Chinese Health Study.

The association between soyfood consumption and subsequent bladder cancer risk was investigated in a population-based cohort study, the Singapore Chinese Health Study. As of December 31, 2000, 329,848 person-years of follow-up were accrued. Sixty-one histologically confirmed incident bladder cancer cases were identified. Information on soyfood consumption at baseline was obtained through in-person interviews using a validated dietary questionnaire. Relative risks and 95% confidence intervals were calculated using the Cox proportional hazard regression method. High intake of soyfood was statistically significantly related to an elevated risk of bladder cancer. Relative to the lowest quartile of energy-adjusted total soy intake (<36.9 g/1000 Kcal), the highest quartile of total soy intake (> or =92.5 g/1000 Kcal) was associated with a 2.3-fold increase in bladder cancer risk (95% confidence interval = 1.1-5.1) after adjustment for cigarette smoking and level of education. Similar results were obtained for intakes of soy protein and soy isoflavones. The soyfood-bladder cancer risk association did not differ significantly between men and women and was not explained by other dietary factors. The soy-cancer relationship became stronger when the analysis was restricted to subjects with longer (> or =3 years) duration of follow-up. To our knowledge, this is the first epidemiological report on the effect of dietary soy on bladder cancer risk.

Age Distribution↗

PubMedDate not supplied

Effect of reproductive hormones on ovarian epithelial tumors: II. Effect on angiogenic activity.

Menstrual cycle activity predisposes to ovarian epithelial tumors based on numerous epidemiological studies. We showed that the hormones involved in menstrual cycle regulation modulate cell cycle activity in these tumors in an accompanying paper. We investigated whether such hormones could also influence angiogenesis, an important determinant of tumor progression, in the same tumors. Treatment with progesterone (P4) stimulated VEGF protein secretion in 4 of 5 ovarian carcinoma cell lines examined. Northern blot analyses performed in MCV50 cells showed that this effect was accompanied by increased VEGF mRNA levels. P4 also stimulated VEGF promoter activity in these cells. Estradiol (E2) showed a similar, but substantially smaller effect on VEGF secretion which was additive to that of P4. Conditioned medium from P4-treated cells strongly stimulated angiogenesis on chicken chorio-allantoic membranes. Incubating the conditioned medium with a neutralizing anti-VEGF antibody, but not with non-specific immunoglobulins abolished this effect. Angiogenic activity was not altered by treatment of the membranes with P4 directly. We conclude that P4 can stimulate angiogenic activity via induction of VEGF secretion in some ovarian epithelial tumors. Therapeutic use of progestins may be most effective when administered in combination with an anti-angiogenic agent, at least against a subset of ovarian carcinomas.

Allantois↗