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Mimi C Yu

Publications and source records attributed to Mimi C Yu.

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↗
PubMed2007

Body size, hormone therapy and risk of breast cancer in Asian-American women.

Historically, breast cancer rates have been low in Asia but rates have increased substantially in Asian-Americans for reasons that are not well understood. The authors conducted a population-based case-control study of breast cancer in Los Angeles County, which included 1,277 (450 Chinese, 352 Japanese, 475 Filipinos) women with incident, histologically confirmed breast cancer and 1,160 control subjects (486 Chinese, 311 Japanese, 363 Filipinos). A detailed in-person interview was conducted, which included questions on menopausal hormone therapy (HT) use, height, weight in each decade of life and reproductive factors. Breast cancer risk increased with increasing recent weight in postmenopausal women (p trend = 0.015). There was a significant 16% (95% CI = 2-35%) increase in risk per 10 kg of body weight in postmenopausal women. In both premenopausal and postmenopausal women, risk increased with increasing waist to hip ratio; this remained statistically significant after adjustment for recent weight in all subjects combined (p trend = 0.042). The increased risk associated with high recent weight in postmenopausal women was more apparent for women with high waist to hip ratio (p trend = 0.013). Use of HT was a significant risk factor; risk increased 26% per 5 years of current use of estrogen and progestin therapy (p trend = 0.017). The increased risk associated with high body weight was observed irrespective of HT use. Use of HT and high body size might have contributed to the rapid increase of breast cancer in Asian-Americans.

Adult↗
PubMed2006

Detection and quantification of 4-ABP adducts in DNA from bladder cancer patients.

We analyzed bladder DNA from 27 cancer patients for dG-C8-4-aminobiphenyl (dG-C8-ABP) adducts using the liquid chromatography tandem mass spectrometry method with a 700 attomol (1 adduct in 10(9) bases) detection limit. Hemoglobin (Hb) 4-aminobiphenyl (4-ABP) adduct levels were measured by gas chromatography-mass spectrometry. After isolation of dG-C8-ABP by immunoaffinity chromatography and further purification, deuterated (d9) dG-C8-ABP (MW=443 Da) was added to each sample. Structural evidence and adduct quantification were determined by selected reaction monitoring, based on the expected adduct ion [M+H+]+1, at m/z 435 with fragmentation to the product ion at m/z 319, and monitoring of the transition for the internal standard, m/z 444-->328. The method was validated by analysis of DNA (100 microg each) from calf thymus; livers from ABP-treated and untreated rats; human placentas; and TK6 lymphoblastoid cells. Adduct was detected at femtomol levels in DNA from livers of ABP-treated rats and calf thymus, but not in other controls. The method was applied to 41 DNA samples (200 microg each) from 27 human bladders; 28 from tumor and 14 from surrounding non-tumor tissue. Of 27 tissues analyzed, 44% (12) contained 5-80 dG-C8-ABP adducts per 10(9) bases; only 1 out of 27 (4%) contained adduct in both tumor and surrounding tissues. The Hb adduct was detected in samples from all patients, at levels of 12-1960 pg per gram Hb. There was no correlation between levels of DNA and Hb adducts. The presence of DNA adducts in 44% of the subjects and high levels of Hb adducts in these non-smokers indicate environmental sources of exposure to 4-ABP.

Aminobiphenyl Compounds↗
PubMed2006

GRP78 as a novel predictor of responsiveness to chemotherapy in breast cancer.

The discovery of predictive factors for chemoresistance is critical for improving adjuvant therapy for cancer patients. The 78-kDa glucose-regulated protein (GRP78), widely used as an indicator of the unfolded protein response (UPR), is induced in the tumor microenvironment. In vitro studies suggest that GRP78 confers chemoresistance to topoisomerase inhibitors, such as Adriamycin (doxorubicin). Here, we report on a retrospective cohort study of 127 stage II and III breast cancer patients who were treated with Adriamycin-based chemotherapy. Archival tumor specimens were available for analysis and the relationship of GRP78 expression level to "time to recurrence" (TTR), used as a surrogate marker for drug resistance, was examined. Our data show that 67% of the study subjects expressed high level of GRP78 in their tumors before the initiation of chemotherapy and suggest an association between GRP78 positivity and shorter TTR [hazard ratio (HR), 1.78; P = 0.16]. Interestingly, subgroup analysis reveals that the HR for the GRP78-positive group increased significantly among patients who did not receive further taxane treatment (HR, 3.00; P = 0.022) and among mastectomy patients (HR, 3.33; P = 0.027). The HR was even stronger among mastectomy patients who did not receive further taxane treatment (HR, 4.82; P = 0.010). The use of GRP78 as a predictor for chemoresponsiveness and the potential interaction of GRP78 and/or the UPR pathways with taxanes warrant larger studies.

Antineoplastic Agents↗
PubMed2006

The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese Health Study.

Cyclin D1 (CCND1) regulates cellular decision between proliferation and growth arrest. Despite the functional relevance of the CCND1 A870G single nucleotide polymorphism (SNP) published results on its association with colorectal cancer (CRC) were inconsistent. We examined the association between this CCND1 genotype and CRC in the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63,000 Chinese men and women. We explored the hypothesis that inconsistency regarding the CCND1/CRC association may be attributable to the modifying effect of additional CRC risk factors. Since GSTM1/GSTT1 genotype and dietary isothiocyanate (ITC) intake had previously been identified as CRC risk factors in this cohort, we now explored if they influenced the CCND1/CRC association. In a nested case-control study within the Singapore Cohort, genomic DNA collected from 300 incident CRC cases and 1169 controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 polymorphisms. Unconditional logistic regression was used to assess genotype effects on cancer risk. No main effect of CCND1 was observed, yet the CCND1 effect was influenced by ITC intake and GST genotypes. The presence of at least one CCND1 A-allele was associated with increased risk among low dietary ITC consumers (intake below median value for the cohort) with a high-activity GST profile (>or=2 of the 3 GST genotypes classified non-null or high-activity) [odds ratio (OR)=2.05; 95% confidence interval (CI), 1.10-3.82]. In contrast, the presence of at least one A-allele was associated with a decreased risk among all remaining subjects (OR=0.56; 0.36-0.86) (P for interaction=0.01). Recent studies indicate that ITCs inhibit cell proliferation and cause apoptosis through pro-oxidant properties. The results of our current study on CRC and those of our previous breast cancer study are compatible with the notion of oxidative stress in target cells as important determinant of direction and magnitude of the CCND1 effect.

Base Sequence↗
PubMed2006

Vapor, dust, and smoke exposure in relation to adult-onset asthma and chronic respiratory symptoms: the Singapore Chinese Health Study.

Occupational factors contribute to a significant fraction of respiratory disease and symptoms. The authors evaluated the role of occupational exposures in asthma, chronic bronchitis, and respiratory symptoms in the Singapore Chinese Health Study, a population-based cohort of adults aged 45-74 years at enrollment in 1993-1998. Information on occupations and occupational exposures was collected at enrollment for 52,325 subjects for whom respiratory outcomes were obtained via follow-up interviews in 1999-2004. Exposure to dusts from cotton, wood, metal, minerals, and/or asbestos was associated with nonchronic cough and/or phlegm (odds ratio (OR) = 1.19, 95% confidence interval (CI): 1.08, 1.30), chronic bronchitis (OR = 1.26, 95% CI: 1.01, 1.57), and adult-onset asthma (OR = 1.14, 95% CI: 1.00, 1.30). Cotton dust was the major contributor to respiratory symptoms. Vapor exposure from chemical solvents, dyes, cooling oils, paints, wood preservatives, and/or pesticides was associated with nonchronic cough or phlegm (OR = 1.14, 95% CI: 1.03, 1.27), chronic dry cough (OR = 1.55, 95% CI: 1.19, 2.01), and adult-onset asthma (OR = 1.34, 95% CI: 1.15, 1.56). Chemical solvents, cooling oils, and pesticides were the major contributors to respiratory symptoms. These data support the role of occupational exposures in the etiology of respiratory illness in a population-based cohort in Singapore with a low prevalence of atopic illness.

Aged↗
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

Association between circulating white blood cell count and cancer mortality: a population-based cohort study.

BACKGROUND: Inflammatory processes are implicated in the development and progression of cancer. However, it is not clear whether systemic markers of inflammation predict cancer. We examined the prospective relationship between circulating white blood cell (WBC) count and cancer mortality. METHODS: Population-based cohort study of 3189 individuals, aged 49 to 84 years and free of cancer at the baseline examination (January 1, 1992, to December 31, 1994), in the Blue Mountains region, west of Sydney, Australia. The main outcome of interest was all cancer mortality ascertained from vital status as of December 31, 2001. RESULTS: Higher WBC count was found to be associated with all cancer mortality. In proportional hazards models adjusting for age, sex, education, body mass index, hematocrit level, alcohol consumption, physical inactivity, smoking, weekly aspirin use, diabetes mellitus or fasting hyperglycemia status, and fasting glucose levels, the multivariable relative risk of all cancer mortality comparing quartile 4 of WBC count ( > or = 7400 cells/microL) with quartile 1 (< or = 5300 cells/microL) was 1.73 (95% confidence interval [CI], 1.18-2.55). In subgroup analyses, the relative risk of cancer mortality comparing quartile 4 of WBC count with quartile 1 was higher among those with diabetes or fasting hyperglycemia (3.03 [95% CI, 1.01-9.15]) than among those with normoglycemia (1.68 [95% CI, 1.12-2.52]). Also, the relative risk of cancer mortality associated with joint exposure to quartile 4 of WBC count and aspirin nonuse was 2.42 (95% CI, 1.46-4.01) compared with their absence. CONCLUSION: These data provide new epidemiological evidence of an association between circulating WBC count, a widely available marker of inflammation, and subsequent cancer mortality.

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

Tea, hormone-related cancers and endogenous hormone levels.

Tea is one of the most popular beverages consumed around the world, second only to water. There has been substantial interest in the potential role of tea in cancer prevention, particularly in respiratory and gastrointestinal tract cancers. Recent epidemiological data have linked tea intake to reduced risk of hormone-related cancers, including breast, ovarian and prostate cancers. Based on sparse data, there is suggestion that tea intake may influence circulating hormone levels, providing a plausible mechanism whereby tea intake may influence risk of hormone-related cancers. The major objectives of this paper are to review the epidemiological evidence on tea and risk of breast, ovarian, and prostate cancers as well as the human and non-human studies on tea and circulating hormone levels. We pay special attention to some of the limitations of the human studies and discuss future research needs.

Animals↗
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

Prospective study of dietary patterns and persistent cough with phlegm among Chinese Singaporeans.

RATIONALE: Using principal components analysis to examine dietary patterns complements the evaluation of individual food and nutrient intake in relation to health outcomes, but has not yet been applied to nonmalignant respiratory disease or symptoms. OBJECTIVE: To examine the relation between patterns of dietary intake at baseline and new onset of persistent cough with phlegm in a population-based cohort of Singapore Chinese. METHODS: A 165-item validated food frequency questionnaire was administered in-person at baseline in 1993. We identified 623 cases of incident cough with phlegm among 52,325 subjects by telephone interview from 1999 through 2004. We identified two distinct food patterns: a "meat-dim sum" pattern characterized by pork and chicken dim sum foods and noodle dishes, and a "vegetable-fruit-soy" pattern characterized by vegetables, fruit, and soyfood items. MAIN RESULTS: The meat-dim sum pattern was positively associated with new-onset cough with phlegm (odds ratio, 1.43; 95% confidence interval, 1.08, 1.89; comparing fourth to first quartile, p for trend = 0.02), after adjustment for age, sex, total energy intake, smoking, education, and nonstarch polysaccharide intake, a protective factor for cough with phlegm in this cohort. Weaker associations were seen for more chronic symptoms and for incident asthma. A weak inverse association for the vegetable-fruit-soy pattern disappeared after adjustment for nonstarch polysaccharide intake. CONCLUSION: A diet rich in meats, sodium, and refined carbohydrates may increase risk of developing cough with phlegm, independently of the apparent beneficial effects of a diet high in fiber in this Singapore Chinese cohort.

Aged↗
PubMed2005

Effect of glutathione-S-transferase polymorphisms on the cancer preventive potential of isothiocyanates: an epidemiological perspective.

Isothiocyanates (ITCs) are widely distributed in cruciferous vegetables and are biologically active against chemical carcinogenesis due to their ability to induce phase II conjugating enzymes. Among these is the glutathione-S-transferase (GST) family of enzymes, which in turn catalyzes the metabolism of ITCs, for which it has high substrate specificity. A recent body of epidemiologic data on the inverse association between cruciferous vegetable/ITC intake and cancers of the colo-rectum, lung and breast, also support that this protective effect is greater among individuals who possess the GSTM1 or T1 null genotype, and who would be expected to accumulate higher levels of ITC at the target tissue level, a pre-requisite for their enzyme-inducing effects. The association between ITC and cancer, and its modification by GST status, is most consistent for lung cancer and appears to be strongest among current smokers. Within limits, a comparison between groups which have been stratified by GST genotype may be less susceptible to confounding by other variables, given the random assortment of genes in gametogenesis. While a more complete understanding of the overall effects on health will need to take into account other components such as indoles and anti-oxidants, the interaction between ITC intake and GST genotype may provide a firmer basis to support a biologically significant role for ITC in cruciferous vegetables.

Anticarcinogenic Agents↗
PubMed2005

Sex differential in methylation patterns of selected genes in Singapore Chinese.

To date there have been few reports of a gender difference in methylation levels of genes. When examining the methylation levels of four autosomal genes (ESR1, MTHFR, CALCA and MGMT) in the white blood cells of a random sample of Singapore Chinese Health Study cohort participants (n = 291), we encountered an unexpected gender differential. Using MethyLight technology, we calculated a gene-specific percentage of methylated reference (PMR) value, which quantified the relative level of gene methylation for each study subject (134 males and 157 females). Two summary methylation indices were constructed by assigning gene-specific rank scores. We then used ANCOVA to compare logarithmically transformed individual PMR values and summary methylation indices by age and gender simultaneously. Adjustment was made for plasma homocysteine. For ESR1, for which a large proportion of subjects were negative for methylation, we also used polytomous regression to compare methylation across age and gender. Increasing age and the male gender independently predicted increasing PMR values for CALCA and MGMT. For the MTHFR gene, male gender was associated with higher PMR values (P = 0.002), while age was not (P = 0.75). Neither age nor gender had any statistically significant influence on the PMR values for ESR1 (P = 0.13 and 0.96, respectively). Our data suggest that gender is at least as strong a predictor of methylation level in the four genes under study as age, with males showing higher PMRs.

Age Factors↗
PubMed2005

The effect of cyclin D1 (CCND1) G870A-polymorphism on breast cancer risk is modified by oxidative stress among Chinese women in Singapore.

Cyclin D1 (CCND1), an intracellular cell-cycle regulatory protein with checkpoint function, can promote cell proliferation or induce growth arrest and apoptosis depending on the cellular context. We hypothesized that the direction of the association between the (CCND1) G870A-polymorphism and breast cancer risk may be modified by dietary and genetic factors influencing the oxidant-antioxidant balance, such as a dietary pattern with a high intake of n-6 fatty acids and a low intake of n-3 fatty acids, or a genetic profile that is deficient in glutathione S-transferases. We tested our hypothesis in a case-control study nested into the Singapore Chinese Health Study, a prospective investigation of diet and cancer in 63,000 Chinese men and women. Genomic DNA collected from 258 incident cases of breast cancer and 670 female cohort controls was examined for CCND1, GSTM1, GSTT1 and GSTP1 genes using fluorogenic 5'-nuclease assay. Unconditional logistic regression models were used to assess the effects with adjustment for potential confounders. All statistical tests were two-sided. The heterozygous CCND1 GA genotype significantly reduced the breast cancer risk in all subjects (OR=0.67, 95% CI 0.45-0.99) when compared with the GG genotype. The association was restricted to women with a high (above median value) intake level of n-6 fatty acids (OR=0.51, 95% CI 0.30-0.87), a low (below median value) intake level of the antagonistic marine n-3 fatty acids (OR=0.54, 95% CI 0.32-0.93) or a total lack of the antioxidative GSTM1 (OR=0.44, 95% CI 0.25-0.80) or GSTT1 genes (OR=0.46, 95% CI 0.24-0.87). The effects were consistently stronger in cases with advanced disease. The AA genotype did not affect breast cancer risk. The results of this study are compatible with the hypothesis that the oxidant-antioxidant balance in cells is an important determinant of the direction of the cyclin D1 effect, leading either to cell proliferation or cell death.

Adult↗