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1.
Int J Cancer ; 147(7): 1917-1927, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32222976

RESUMO

Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case-control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.e., sum of choline, betaine and methionine), dimethylglycine and trimethylamine N-oxide (TMAO) with pancreatic cancer risk. In the Shanghai cohort, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of choline, betaine, methionine, total methyl donors and TMAO were 0.27 (0.11-0.69), 0.57 (0.31-1.05), 0.50 (0.26-0.96), 0.37 (0.19-0.73) and 2.81 (1.37-5.76), respectively, compared to the lowest quartile. The corresponding figures in the Singapore cohort were 0.85 (0.23-3.17), 0.50 (0.17-1.45), 0.17 (0.04-0.68), 0.33 (0.10-1.16) and 1.42 (0.50-4.04). The inverse associations of methionine and total methyl donors including choline, betaine and methionine with pancreatic cancer risk in both cohorts support that DNA repair and methylation play an important role against the development of pancreatic cancer. In the Shanghai cohort, TMAO, a gut microbiota-derived metabolite of dietary phosphatidylcholine, may contribute to higher risk of pancreatic cancer, suggesting a modifying role of gut microbiota in the dietary choline-pancreatic cancer risk association.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31861047

RESUMO

The combination of poor diet and exposure to secondhand smoke may increase hemoglobin A1c (HbA1c) levels, but few studies have explored this interaction. We explored an interaction among 574 never-smoking adults from the Singapore Chinese Health Study. At baseline (age 59 ± 8 years), intakes of omega-3 polyunsaturated fatty acids, vitamin C, vitamin E and fiber were estimated using a modified food frequency questionnaire. At follow-up (age 64 ± 9 years), HbA1c and cotinine were measured. A product term between cotinine (above or below the median value) and each nutrient (high or low intake) was included in separate linear regression models with HbA1c as the outcome. HbA1c among those with high cotinine and low omega-3 polyunsaturated fatty acids intakes were higher than would be expected due to the individual effects alone (p-for-interaction = 0.05). Among those with lower intakes of omega-3 polyunsaturated fatty acids, high cotinine levels were associated with 0.54% higher HbA1c levels (95% confidence interval [CI]: 0.02, 1.06). Conversely, among those with higher intakes of omega-3 polyunsaturated fatty acids, HbA1c differ not differ by exposure (-0.09%; 95% CI: -0.45, 0.30). No evidence of interaction was observed for other nutrients. Diets high in omega-3 polyunsaturated fatty acids may ameliorate secondhand smoke-induced increases in HbA1c.


Assuntos
Dieta/efeitos adversos , Hemoglobina A Glicada/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Idoso , Estudos de Coortes , Cotinina/urina , Fibras na Dieta/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Singapura , Vitamina E/administração & dosagem
3.
Cancer Causes Control ; 30(8): 847-857, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154549

RESUMO

PURPOSE: Soy isoflavones and tea catechins have immunomodulating and chemopreventive properties relevant for cervical carcinogenesis; however, there are limited epidemiologic data on the relationship of soy and tea consumption with cervical cancer risk. The aim of our study was to examine effects of soy and tea intake on cervical cancer risk among Singapore Chinese women. METHODS: The association between intake of soy and tea drinking and cervical cancer risk was investigated in a prospective, population-based cohort of 30,744 Chinese women in Singapore with an average 16.7 years of follow-up and 312 incident cervical cancer cases. Multivariable proportional hazard models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of cervical cancer associated with intake levels of soy and tea. RESULTS: High intake of soy alone was associated with a statistically borderline significant 20% reduced risk of cervical cancer (HR 0.80, 95% CI 0.61, 1.05) while green tea alone was not (HR 0.97, 95% CI: 0.76, 1.22). In stratified analysis, high intake of soy was associated with a statistically significant decrease in cervical cancer risk among green tea drinkers (HR 0.43; 95% CI 0.28, 0.69) but not among non-drinkers of green tea. The difference in the soy-cervical cancer risk association between green tea drinkers and non-drinkers was statistically significant (p for interaction = 0.004). This inverse association between soy intake and cervical cancer risk remained after further adjustment for human papillomavirus serostatus. Black tea consumption was not associated with cervical cancer risk. CONCLUSIONS: These findings suggest that a protective effect of soy against cervical cancer development may depend on green tea constituents.


Assuntos
Alimentos de Soja , Chá , Neoplasias do Colo do Útero/epidemiologia , Idoso , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Singapura/epidemiologia
4.
Oncotarget ; 10(19): 1760-1774, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30956756

RESUMO

The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.

5.
Transl Psychiatry ; 9(1): 123, 2019 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-30923322

RESUMO

Neuropsychiatric symptoms (NPS) are a risk factor for cognitive impairment and are associated with cortical ß-amyloid (Aß) deposition. We conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging to examine the frequency of NPS among cognitively unimpaired (CU) and mild cognitive impairment (MCI) participants who either have normal (A-) or abnormal (A+) Aß deposition. We also investigated whether combined presence of MCI and amyloid positivity (MCI/A+) is associated with greater odds of having NPS as compared to CU/A- (defined as reference group). Participants were 1627 CU and MCI individuals aged ≥ 50 years (54% males; median age 73 years). All participants underwent NPS assessment (Neuropsychiatric Inventory Questionnaire (NPI-Q); Beck Depression Inventory II (BDI-II); Beck Anxiety Inventory (BAI)) and 11C-PiB-PET. Participants with an SUVR > 1.42 were classified as A+. We conducted multivariable logistic regression analyses adjusted for age, sex, education, and APOE ε4 genotype status. The sample included 997 CU/A-, 446 CU/A+, 78 MCI/A-, and 106 MCI/A+ persons. For most NPS, the highest frequency of NPS was found in MCI/A+ and the lowest in CU/A-. The odds ratios of having NPS, depression (BDI ≥ 13), or anxiety (BAI ≥ 8, ≥ 10) were consistently highest for MCI/A+ participants. In conclusion, MCI with Aß burden of the brain is associated with an increased risk of having NPS as compared to MCI without Aß burden. This implies that the underlying Alzheimer's disease biology (i.e., cerebral Aß amyloidosis) may drive both cognitive and psychiatric symptoms.


Assuntos
Envelhecimento , Peptídeos beta-Amiloides/análise , Ansiedade/diagnóstico , Disfunção Cognitiva/diagnóstico , Depressão/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Ansiedade/psicologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Disfunção Cognitiva/psicologia , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons
6.
PLoS One ; 13(5): e0196465, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29734388

RESUMO

BACKGROUND: Serum pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B6 status and risk of pancreatic cancer is lacking. METHODS: A nested case-control study involving 187 incident cases of pancreatic cancer and 362 individually matched controls were conducted within two prospective cohorts to evaluate the associations between kynurenine metabolites in pre-diagnostic serum samples and risk of pancreatic cancer. RESULTS: Higher serum concentrations of 3-hydroxyanthranilic acid (HAA) and the HAA:3-hydroxykynurenine (HK) ratio (a measure for in vivo functional status of PLP) were significantly associated with reduced risk of pancreatic cancer. Compared with the lowest tertile, odds ratios (95% confidence intervals) of pancreatic cancer for the highest tertile was 0.62 (0.39, 1.01) for HAA, and 0.59 (0.35-0.98) for the HAA:HK ratio, after adjustment for potential confounders and serum PLP (both Ps for trend<0.05). The kynurenine:tryptophan ratio or neopterin was not significantly associated with pancreatic cancer risk. CONCLUSIONS: The inverse association between HAA or the HAA:HK ratio and risk of pancreatic cancer supports the notion that functional status of PLP may be a more important measure than circulating PLP alone for the development of pancreatic cancer.


Assuntos
Ácido 3-Hidroxiantranílico/análise , Cinurenina/análogos & derivados , Cinurenina/metabolismo , Biomarcadores/sangue , Estudos de Casos e Controles , China , Feminino , Humanos , Cinurenina/análise , Cinurenina/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Neoplasias Pancreáticas/metabolismo , Estudos Prospectivos , Fosfato de Piridoxal/sangue , Fatores de Risco , Vitamina B 6/sangue
7.
BMC Cancer ; 18(1): 220, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29471809

RESUMO

BACKGROUND: Obesity has been proposed as a potential protective factor against lung cancer. We examined the association between BMI and lung cancer risk in a pooled analysis based on nested case-control studies from four cohort studies. METHODS: A case-control study was nested within four cohorts in USA, Europe, China and Singapore that included 4172 cases and 8471 control subjects. BMI at baseline was calculated as weight in kilograms divided by height in meters squared (kg/m2), and classified into 4 categories: underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30) and obese (≥30). Odds ratios (ORs) and 95% confidence intervals (CIs) for BMI-lung cancer associations were estimated using unconditional logistic regression, adjusting for potential confounders. RESULTS: Considering all participants, and using normal weight as the reference group, a decreased risk of lung cancer was observed for those who were overweight (OR 0.77, 95% CI: 0.68-0.86) and obese (OR 0.69, 95% CI: 0.59-0.82). In the stratified analysis by smoking status, the decreased risk for lung cancer was observed among current, former and never smokers (P for interaction 0.002). The adjusted ORs for overweight and obese groups were 0.79 (95% CI: 0.68-0.92) and 0.75 (95% CI: 0.60-0.93) for current smokers, 0.70 (95% CI: 0.53-0.93) and 0.55 (95% CI: 0.37-0.80) for former smokers, 0.77 (95% CI: 0.59-0.99), and 0.71 (95% CI: 0.44-1.14) for never smokers, respectively. While no statistically significant association was observed for underweight subjects who were current smokers (OR 1.24, 95% CI: 0.98-1.58), former smokers (OR 0.27, 95% CI: 0.12-0.61) and never smokers (OR 0.83, 95% CI: 0.5.-1.28). CONCLUSION: The results of this study provide additional evidence that obesity is associated with a decreased risk of lung cancer. Further biological studies are needed to address this association.


Assuntos
Neoplasias Pulmonares/etiologia , Sobrepeso/complicações , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Fatores de Risco , Fumar/efeitos adversos
8.
J Natl Cancer Inst ; 110(1)2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28922778

RESUMO

Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.


Assuntos
Ácido Fólico/sangue , Neoplasias Pulmonares/epidemiologia , Metionina/sangue , Vitamina B 6/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Austrália/epidemiologia , Estudos de Casos e Controles , Cotinina/sangue , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Fatores Sexuais , Fumar/sangue , Fumar/epidemiologia , Estados Unidos/epidemiologia
9.
Carcinogenesis ; 39(3): 336-346, 2018 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-29059373

RESUMO

Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Fumar/efeitos adversos , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu , Interação Gene-Ambiente , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
10.
Cancer Causes Control ; 29(1): 51-62, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29124543

RESUMO

PURPOSE: Mechanistic and observational data together support a role for prolactin in breast cancer development. Determinants of prolactin in Asian populations have not been meaningfully explored, despite the lower risk of breast cancer in Asian populations. METHODS: Determinants of plasma prolactin were evaluated in 442 postmenopausal women enrolled in the Singapore Chinese Health Study, a population-based prospective cohort study. At baseline all cohort members completed an in-person interview that elicited information on diet, menstrual and reproductive history, and lifestyle factors. One year after cohort initiation we began collecting blood samples. Quantified were plasma concentrations of prolactin, estrone, estradiol, testosterone, androstenedione, and sex hormone-binding globulin (SHBG). Analysis of covariance method was used for statistical analyses with age at blood draw, time since last meal, and time at blood draw as covariates. RESULTS: Mean prolactin levels were 25.1% lower with older age at menarche (p value = 0.001), and 27.6% higher with greater years between menarche and menopause (p value = 0.009). Prolactin levels were also positively associated with increased sleep duration (p value = 0.005). The independent determinants of prolactin were years from menarche to menopause, hours of sleep, and the plasma hormones estrone and SHBG (all p values < 0.01). CONCLUSION: The role of prolactin in breast cancer development may involve reproductive and lifestyle factors, such as a longer duration of menstrual cycling and sleep patterns.


Assuntos
Neoplasias da Mama/sangue , Menopausa/sangue , Prolactina/sangue , Idoso , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Estilo de Vida , Menarca , Ciclo Menstrual , Pessoa de Meia-Idade , Estudos Prospectivos , História Reprodutiva , Fatores de Risco , Globulina de Ligação a Hormônio Sexual/análise , Singapura , Sono
11.
Int J Cancer ; 142(12): 2425-2434, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29238985

RESUMO

Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5'-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case-control study consisting of 5,364 matched case-control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4thvs.1st ) was 1.25 (95% confidence interval, 1.10-1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.


Assuntos
Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Vitamina B 6/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
12.
Int J Cancer ; 141(12): 2450-2461, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-28842914

RESUMO

Accumulating evidence suggests that the aggregation of common metabolic conditions (high blood pressure, diabetes and dyslipidemia) is a risk factor for breast cancer. Breast cancer incidence has risen steadily in Asian American women, and whether these metabolic conditions contribute to breast cancer risk in certain Asian American subgroups is unknown. We investigated the role of physician-diagnosed hypertension, high cholesterol and diabetes separately, and in combination, in relation to the risk of breast cancer in a population-based case-control study of 2,167 Asian Americans diagnosed with breast cancer and 2,035 age and ethnicity matched control women in Los Angeles County. Compared to Asian American women who did not have any of the metabolic conditions, those with 1, 2 or 3 conditions showed a steady increase in risk (respective odds ratios were 1.12, 1.42 and 1.62; P trend = 0.001) with adjustment for covariates including body mass index. Similar significant trends were observed in Filipina Americans (P trend = 0.021), postmenopausal women (P trend =0.001), Asian women who were born in the United States (US) (P trend = 0.052) and migrants who have lived in the US for at least 20 years (P trend = 0.004), but not migrants who lived in the US for <20 years (P trend = 0.64). These results suggest that westernization in lifestyle (diet and physical inactivity) and corresponding increase in adiposity have contributed to the rising prevalence of these metabolic conditions, which in turn, are associated with an increase in breast cancer.


Assuntos
Americanos Asiáticos/classificação , Neoplasias da Mama/epidemiologia , Síndrome Metabólica/complicações , Adulto , Distribuição por Idade , Idoso , Neoplasias da Mama/etnologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , China/etnologia , Feminino , Humanos , Incidência , Japão/etnologia , Estilo de Vida , Los Angeles/epidemiologia , Síndrome Metabólica/etnologia , Pessoa de Meia-Idade , Razão de Chances , Filipinas/etnologia
13.
Cancer Prev Res (Phila) ; 10(10): 571-579, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28765194

RESUMO

Liver injury effects of green tea-based products have been reported in sporadic case reports. However, no study has examined systematically such adverse effects in an unbiased manner. We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk. The current analysis examined the effect of GTE consumption on liver injury in 1,021 participants (513 in GTE and 508 in placebo arm) with normal baseline levels of liver enzymes. Among women in the GTE arm, alanine aminotransferase (ALT) increased by 5.4 U/L [95% confidence interval (CI), 3.6-7.1] and aspartate aminotransferase increased by 3.8 U/L (95% CI, 2.5-5.1), which were significantly higher than those among women in the placebo arm (both P < 0.001). Overall, 26 (5.1%) women in GTE developed moderate or more severe abnormalities in any liver function measure during the intervention period, yielding an OR of 7.0 (95% CI, 2.4-20.3) for developing liver function abnormalities as compared with those in the placebo arm. ALT returned to normal after dechallenge and increased again after one or more rechallenges with GTE. The rise-fall pattern of liver enzyme values following the challenge-dechallenge cycles of GTE consumption strongly implicates the effect of high-dose GTE on liver enzyme elevations. Cancer Prev Res; 10(10); 571-9. ©2017 AACR.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/sangue , Suplementos Nutricionais/efeitos adversos , Fígado/efeitos dos fármacos , Extratos Vegetais/efeitos adversos , Chá/química , Idoso , Alanina Transaminase/sangue , Antioxidantes/efeitos adversos , Aspartato Aminotransferases/sangue , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/prevenção & controle , Catequina/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Método Duplo-Cego , Feminino , Humanos , Fígado/enzimologia , Testes de Função Hepática , Pessoa de Meia-Idade , Placebos , Extratos Vegetais/química , Estados Unidos
14.
Eur J Cancer Prev ; 26(6): 469-475, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28542077

RESUMO

Singapore has experienced a marked increase in colorectal cancer incidence over the past 40 years. Evidence from prospective studies in Western Europe and the USA suggests that low physical activity and high amounts of sedentary time are associated with increased colorectal cancer risk. The aim of this study is to evaluate these relationships in an Asian population. The Singapore Chinese Health Study enrolled 63 257 adults between 1993 and 1998. At enrollment, participants reported past year physical activity and time spent sitting. Incident colorectal cancers (n=1994) were identified through 31 December 2014. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders. Any strenuous-vigorous or moderate physical activity was reported by 13.7 and 22.1% of the cohort, respectively. Strenuous-vigorous physical activity was associated with statistically significant reduced colorectal cancer risk (HR=0.85; 95% CI: 0.74-0.99 for ≥0.5 h/week vs. none), but moderate was not. In analysis stratified by time spent watching television, an inverse relationship between moderate physical activity and colorectal cancer risk (HR=0.86; 95% CI: 0.72-1.01 for ≥0.5 h/week vs. none) was observed for those who reported at least 3 h/day sitting watching television (Pinteraction=0.042). Participation in strenuous-vigorous physical activity, such as jogging, swimming, or heavy manual labor, was associated with reduced colorectal cancer risk among Singapore Chinese. Further research on physical activity and sedentary behaviors, independently and in combination, and colorectal cancer risk in Asian populations is needed.


Assuntos
Grupo com Ancestrais do Continente Asiático/etnologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etnologia , Exercício Físico/fisiologia , Comportamento Sedentário/etnologia , Idoso , Estudos de Coortes , Neoplasias Colorretais/prevenção & controle , Feminino , Seguimentos , Inquéritos Epidemiológicos/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Singapura/etnologia
15.
Am J Clin Nutr ; 105(6): 1314-1326, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28424186

RESUMO

Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies.Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions.Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users.Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.


Assuntos
Carbono/sangue , Cinurenina/sangue , Vitamina A/sangue , Complexo Vitamínico B/sangue , Vitamina D/sangue , alfa-Tocoferol/sangue , Idoso , Ásia , Austrália , Biomarcadores/sangue , Estudos Transversais , Suplementos Nutricionais , Feminino , Humanos , Laboratórios , Masculino , Pessoa de Meia-Idade , Países Escandinavos e Nórdicos , Triptofano/sangue , Estados Unidos
16.
Am J Clin Nutr ; 105(3): 736-745, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28179225

RESUMO

Background: Findings on the relation between fruit consumption and the risk of type 2 diabetes mellitus (T2DM) have been inconsistent.Objectives: We examined whether the consumption of total, temperate, subtropical, and tropical fruit is associated with T2DM risk and whether differences in the carbohydrate quality of fruit influence T2DM risk in Asians.Design: We included 45,411 participants in the Singapore Chinese Health Study who were 45-74 y old and had no diabetes, cancer, or cardiovascular disease at recruitment (1993-1998). Fruit intake was assessed with the use of a validated food-frequency questionnaire. Physician-diagnosed incident T2DM cases were reported at follow-up 1 (1999-2004) and follow-up 2 (2006-2010) interviews. Cox proportional hazards regression was used to estimate HRs and 95% CIs of diabetes risk.Results: In 494,741 person-years of follow-up, 5207 participants developed T2DM. After adjustment for lifestyle and dietary risk factors, high total fruit consumption was not consistently associated with lower T2DM risk [men: HR of 1.33 (95% CI: 1.04, 1.71) for ≥3 servings/d compared with <1 serving/wk (P-trend = 0.17); women: HR of 0.88 (95% CI: 0.71, 1.11) (P-trend = 0.008); P-interaction = 0.003]. The direct association in men was observed for higher-glycemic index (GI) fruit [HR: 1.51 (95% CI: 1.22, 1.86) for ≥1 serving/d compared with rarely consumed; P-trend = 0.001] but not for lower or moderate GI fruit. In women, the consumption of temperate fruit, but not of subtropical or tropical fruit, was associated with lower T2DM risk [HR: 0.79 (95% CI: 0.67, 0.92) for ≥1 serving/d compared with rarely; P-trend = 0.006].Conclusions: The consumption of temperate fruit, such as apples, was associated with a lower risk of T2DM in women, whereas the consumption of higher-GI fruit, such as bananas, was associated with higher risk in men. The impact of fruit consumption on the risk of diabetes may differ by the type of fruit, which may reflect differences in the glycemic impact or phytochemical content.


Assuntos
Clima , Diabetes Mellitus Tipo 2/etiologia , Dieta , Comportamento Alimentar , Frutas , Índice Glicêmico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Singapura
17.
Int J Epidemiol ; 46(3): 881-893, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28031315

RESUMO

Background: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status. Methods: To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Smoking duration before first birth was positively associated with risk ( P -value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth ( P -value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer ( P -value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident. Conclusions: Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Neoplasias da Mama/epidemiologia , Fumar Cigarros/epidemiologia , Adulto , Idoso , Fumar Cigarros/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , National Cancer Institute (U.S.) , Modelos de Riscos Proporcionais , Receptores Estrogênicos/genética , Fatores de Risco , Estados Unidos
18.
NPJ Precis Oncol ; 1(1): 38, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29872717

RESUMO

Fatty acid composition in plasma captures both dietary intake and endogenous synthesis. Prospective analyses of plasma fatty acid composition are needed to establish the role of monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) on risk of developing colorectal cancer. To evaluate associations between plasma fatty acid composition and colon or rectal cancer risk separately, a nested case-control study of 350 colorectal (211 colon and 139 rectal) cancer cases and an equal number of individually matched control subjects was conducted within the Singapore Chinese Health Study, a cohort of 63,257 men and women recruited between 1993 and 1998. Fatty acids in pre-diagnostic plasma were quantified using gas chromatography-tandem mass spectrometry. Conditional odds ratios (ORs) and 95% confidence intervals (CIs) comparing highest to lowest quartiles are presented. For colon cancer, inverse associations were reported with higher essential PUFAs, α-linolenic acid (OR = 0.41; 95% CI: 0.23, 0.73; Ptrend = 0.005) and linoleic acid (OR = 0.43; 95% CI: 0.23, 0.82; Ptrend = 0.008). Higher desaturase activity in the n-6 PUFA synthesis pathway estimated by the arachidonic:linoleic acid ratio was associated with increased colon cancer risk (OR = 3.53; 95% CI: 1.82, 6.85; Ptrend = 0.006), whereas higher desaturase activity in the MUFA synthesis pathway estimated by the oleic:stearic acid ratio was associated with decreased colon cancer risk (OR = 0.42; 95% CI: 0.19, 0.92; Ptrend = 0.024). There was no significant association between the essential fatty acids or the desaturase indices and rectal cancer risk. Endogenous synthesis of arachidonic and oleic acids has an impact on colon cancer development.

19.
Cancer Causes Control ; 27(12): 1447-1456, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27830400

RESUMO

BACKGROUND: Vitamin B6 is an important enzymatic cofactor in pathways relevant for the development of pancreatic cancer. In order to evaluate vitamin B6 as a preventive factor for pancreatic cancer, a biomarker approach is needed to overcome the limitations inherent in self-reported dietary information. METHODS: To determine whether levels of serum B6 vitamers, including pyridoxal 5'-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (PA), and the PA/(PLP + PL) ratio (PAr), were associated with risk of pancreatic cancer, two nested case-control studies of 187 incident pancreatic cancer cases and 258 individually matched controls were conducted within two prospective cohorts of 81,501 participants in Shanghai, China, and Singapore. PLP, PL, and PA were quantified in pre-diagnostic serum samples. Odds ratios and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for potential confounders. RESULTS: The median (5th-95th percentiles) concentrations of serum PLP among control subjects of the Shanghai and Singapore cohorts were 25.7 (10.0-91.7) nmol/L and 58.1 (20.8-563.0) nmol/L, respectively. In pooled analyses, high serum PLP was associated with a reduced risk of pancreatic cancer (P for trend = 0.048); the adjusted odds ratio for the highest category of PLP (>52.4 nmol/L) was 0.46 (95% CI 0.23, 0.92) compared to vitamin B6 deficiency (<20 nmol/L). No associations were found for serum PL, PA, or PAr with pancreatic cancer risk. CONCLUSIONS: Higher concentrations of PLP may protect against the development of pancreatic cancer. The protective effect may be more apparent in populations with low concentrations of circulating vitamin B6.


Assuntos
Neoplasias Pancreáticas/sangue , Fosfato de Piridoxal/sangue , Piridoxal/sangue , Ácido Piridóxico/sangue , Idoso , Grupo com Ancestrais do Continente Asiático , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/epidemiologia , Estudos Prospectivos , Fatores de Risco , Singapura/epidemiologia , Vitamina B 6/sangue , Complexo Vitamínico B/sangue
20.
Cancer Epidemiol Biomarkers Prev ; 25(12): 1572-1586, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27550750

RESUMO

BACKGROUND: Filipina Americans have one of the highest breast cancer incidence rates among Asian Americans for poorly understood reasons. METHODS: Breast cancer risk factors were investigated in a population-based study of Filipina (790 cases, 587 controls), Japanese (543 cases, 510 controls), and Chinese (913 cases, 904 controls) Americans. Cases were identified by the Los Angeles County Cancer Surveillance Program, and controls were matched to cases on age, ethnicity, and neighborhood. Multivariable conditional logistic regression was performed by Asian ethnicity. RESULTS: In Filipina, Chinese, and Japanese Americans, breast cancer risk decreased significantly with increasing parity (all Ptrend < 0.0001). Breast cancer risk increased with increasing quartiles of cumulative menstrual months in premenopausal (Ptrend = 0.019) and postmenopausal Filipina (Ptrend = 0.008), in premenopausal (Ptrend = 0.0003) but not postmenopausal Chinese (Ptrend = 0.79), and in neither premenopausal (Ptrend = 0.092) nor postmenopausal (Ptrend = 0.75) Japanese Americans. For postmenopausal Filipina and Japanese, greater weight gain since age 18 (Ptrend = 0.019 and 0.053, respectively), high current body mass index (both Ptrend < 0.01), and greater waist circumferences (both Ptrend < 0.04) were statistically significant; these associations were weaker for postmenopausal Chinese women. CONCLUSIONS: Cumulative menstrual months and body size factors were statistically significant risk factors for Filipina. Total menstrual months were associated with breast cancer among Chinese but not for Japanese, while body size factors were significantly associated with risk among Japanese but not among Chinese. IMPACT: Characterization of breast cancer risk factors in Filipina will help to generate hypotheses for their high breast cancer incidence. Cancer Epidemiol Biomarkers Prev; 25(12); 1572-86. ©2016 AACR.


Assuntos
Americanos Asiáticos , Índice de Massa Corporal , Neoplasias da Mama/epidemiologia , Paridade , Adulto , Idoso , Estudos de Casos e Controles , China/etnologia , Feminino , Humanos , Incidência , Japão/etnologia , Los Angeles/epidemiologia , Pessoa de Meia-Idade , Filipinas/etnologia , Fatores de Risco
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