RESUMO
Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and toxicity limits use of these agents. Vitamin D is a potential prevention therapy for both ER+ and ER- disease and is safe with few side effects. This study evaluates the effect of 1-year of vitamin D supplementation on mammographic density (MD), a biomarker of breast cancer risk in a multicenter randomized controlled trial. Premenopausal women with ≥25% MD and no history of cancer were randomly assigned to 2,000 international units (IU) of vitamin D or placebo orally daily for 1 year. Change in percent MD was evaluated using Cumulus software after all participants completed treatment. Three hundred women enrolled between January 2011 and December 2013 with a mean age of 43 and diverse ethnicity [14% Hispanic, 12% African American (AA)]. Supplementation significantly increased vitamin D levels compared with placebo (14.5 ng/mL vs. -1.6 ng/mL; P < 0.0001) with all participants on the vitamin D arm achieving vitamin D sufficiency at 12 months. Vitamin D was safe and well tolerated. After adjustment for baseline MD, the mean between-arm difference (vitamin D vs. placebo) at 1 year was -0.75 (-0.26, 1.76; P = 0.56). A greater effect was seen for women with ≥50% MD and AA women, although neither reached significance. This randomized controlled trial demonstrated significant improvement in vitamin D levels with 2,000 IU for 1 year, with 100% of supplemented women achieving sufficiency. However, a null effect was seen regarding change in MD for premenopausal women (the primary outcome of the study). PREVENTION RELEVANCE: Current therapies for breast cancer prevention only prevent estrogen receptor positive (ER+) disease and are underutilized due to toxicity and side effects. Vitamin D is a potential prevention therapy for both ER+ and ER- disease and is safe with few side effects.
Assuntos
Densidade da Mama , Neoplasias da Mama/prevenção & controle , Suplementos Nutricionais , Vitamina D/administração & dosagem , Adulto , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Método Duplo-Cego , Feminino , Humanos , Mamografia/estatística & dados numéricos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
According to the Nutritional Prevention of Cancer (NPC) trial, a selenized yeast supplement containing selenium, 200 mcg/day, decreased the incidence of total cancer, cancers of the prostate, colon and lung, and cancer mortality. The active agent in the selenized yeast supplement was assumed to be selenomethionine (SEMET), although the supplement had not been well speciated. The SELECT study, largely motivated by the NPC trial, enrolling nearly 40 times as many subjects, showed unequivocally that selenium 200 mcg/day, with selenium in the form of SEMET, does not protect selenium-replete men against prostate or other major cancer. The agent tested by SELECT, pure SEMET, could have been different from the selenized yeast tested in NPC. One of the selenium forms suspected of having chemopreventive effects, and which may have been present in the NPC agent, is methyl selenocysteine (MSC). This study, with 29 selenium-replete patients enrolled in a randomized, double-blind trial, compared the multiple-dose toxicity, pharmacokinetics and pharmacodynamics of MSC and SEMET. Patients were on trial for 84 days. No toxicity was observed. Although SEMET supplementation increased blood selenium concentration more than MSC did, neither form had a more than minimal impact on the two major selenoproteins: selenoprotein P(SEPP1) and glutathione peroxidase(GPX).
Assuntos
Suplementos Nutricionais , Selenocisteína/análogos & derivados , Selenometionina/administração & dosagem , Selenometionina/farmacocinética , Adulto , Idoso , Estudos de Casos e Controles , Quimioprevenção , Monitoramento de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias/prevenção & controle , Selenocisteína/administração & dosagem , Selenocisteína/farmacocinética , Fatores de TempoRESUMO
PURPOSE: Vitamins A, C, and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer. METHODS: The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RRs) were estimated using the Cox proportional hazards model and then combined using a random-effects model. RESULTS: Among 501,857 women, 1,973 cases of ovarian cancer occurred over a median follow-up period of 7-16 years across studies. Dietary and total intakes of each vitamin were not significantly associated with ovarian cancer risk. The pooled multivariate RRs [95% confidence intervals (CIs)] for incremental increases in total intake of each vitamin were 1.02 (0.97-1.07) for vitamin A (increment: 1,300 mcg/day), 1.01 (0.99-1.04) for vitamin C (400 mg/day), 1.02 (0.97-1.06) for vitamin E (130 mg/day), and 1.01 (0.96-1.07) for folate (250 mcg/day). Multivitamin use (vs. nonuse) was not associated with ovarian cancer risk (pooled multivariate RR = 1.00, 95% CI 0.89-1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n = 156 cases), but not with other histological types. CONCLUSION: These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk.
Assuntos
Ácido Ascórbico/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Ácido Fólico/efeitos adversos , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Epiteliais e Glandulares/etiologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Vitamina A/efeitos adversos , Vitamina E/efeitos adversos , Vitaminas/efeitos adversos , Adulto , Carcinoma Epitelial do Ovário , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , América do Norte/epidemiologia , Estudos Prospectivos , RiscoRESUMO
IMPORTANCE: Dental caries is the demineralization of tooth structures by lactic acid from fermentation of carbohydrates by commensal gram-positive bacteria. Cariogenic bacteria have been shown to elicit a potent Th1 cytokine polarization and a cell-mediated immune response. OBJECTIVE: To test the association between dental caries and head and neck squamous cell carcinoma (HNSCC). DESIGN, SETTING, AND PARTICIPANTS: Case-control study in a comprehensive cancer center including all patients with newly diagnosed primary HNSCC between 1999 and 2007 as cases and all patients without a cancer diagnosis as controls. Those with a history of cancer, dysplasia, or immunodeficiency or who were younger than 21 years were excluded. EXPOSURES: Dental caries, fillings, crowns, and endodontic treatments, measured by the number of affected teeth; missing teeth. We also computed an index variable: decayed, missing, and filled teeth (DMFT). MAIN OUTCOMES AND MEASURES: Incident HNSCC. RESULTS: We included 620 participants (399 cases and 221 controls). Cases had a significantly lower mean (SD) number of teeth with caries (1.58 [2.52] vs 2.04 [2.15]; P = .03), crowns (1.27 [2.65] vs 2.10 [3.57]; P = .01), endodontic treatments (0.56 [1.24] vs 1.01 [2.04]; P = .01), and fillings (5.39 [4.31] vs 6.17 [4.51]; P = .04) but more missing teeth (13.71 [10.27] vs 8.50 [8.32]; P < .001) than controls. There was no significant difference in mean DMFT. After adjustment for age at diagnosis, sex, marital status, smoking status, and alcohol use, those in the upper tertiles of caries (odds ratio [OR], 0.32 [95% CI, 0.19-0.55]; P for trend = .001), crowns (OR, 0.46 [95% CI, 0.26-0.84]; P for trend = .03), and endodontic treatments (OR, 0.55 [95% CI, 0.30-1.01]; P for trend = .15) were less likely to have HNSCC than those in the lower tertiles. Missing teeth was no longer associated with HNSCC after adjustment for confounding. CONCLUSIONS AND RELEVANCE: There is an inverse association between HNSCC and dental caries. This study provides insights for future studies to assess potential beneficial effects of lactic acid bacteria and the associated immune response on HNSCC.
Assuntos
Carcinoma de Células Escamosas/complicações , Cárie Dentária/epidemiologia , Neoplasias de Cabeça e Pescoço/complicações , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Cárie Dentária/patologia , Cárie Dentária/terapia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Saúde Bucal , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Selenium is an essential trace element and circulating selenium concentrations have been associated with a wide range of diseases. Candidate gene studies suggest that circulating selenium concentrations may be impacted by genetic variation; however, no study has comprehensively investigated this hypothesis. Therefore, we conducted a two-stage genome-wide association study to identify genetic variants associated with serum selenium concentrations in 1203 European descents from two cohorts: the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening and the Women's Health Initiative (WHI). We tested association between 2,474,333 single nucleotide polymorphisms (SNPs) and serum selenium concentrations using linear regression models. In the first stage (PLCO) 41 SNPs clustered in 15 regions had p < 1 × 10(-5). None of these 41 SNPs reached the significant threshold (p = 0.05/15 regions = 0.003) in the second stage (WHI). Three SNPs had p < 0.05 in the second stage (rs1395479 and rs1506807 in 4q34.3/AGA-NEIL3; and rs891684 in 17q24.3/SLC39A11) and had p between 2.62 × 10(-7) and 4.04 × 10(-7) in the combined analysis (PLCO + WHI). Additional studies are needed to replicate these findings. Identification of genetic variation that impacts selenium concentrations may contribute to a better understanding of which genes regulate circulating selenium concentrations.
Assuntos
Genótipo , Polimorfismo de Nucleotídeo Único , Selênio/sangue , População Branca/genética , Idoso , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To determine whether periodontitis is associated with human papillomavirus (HPV) status of head and neck squamous cell carcinoma (HNSCC). DESIGN AND SETTING: Hospital-based case-control study in a comprehensive cancer center. PATIENTS: Evaluation included all patients diagnosed with incident primary squamous cell carcinoma of the oral cavity, oropharynx, and larynx between 1999 and 2007 for whom tissue samples and dental records were available (N = 124). Patients younger than 21 years and those with a history of cancer were excluded. Periodontitis history was assessed by alveolar bone loss in millimeters from panoramic radiographs by one examiner blinded to cancer status. MAIN OUTCOME MEASURE: The presence of HPV-16 DNA in paraffin-embedded tumor samples was identified by polymerase chain reaction. RESULTS: The prevalence of HPV-positive HNSCC was 50 of 124 patients (40.3%). A higher proportion of oropharyngeal cancers were HPV-positive (32 of 49 [65.3%]) compared with oral cavity (9 of 31 [29.0%]) and laryngeal (9 of 44 [20.5%]) cancers. Each millimeter of alveolar bone loss was associated with 2.6 times increased odds (odds ratio [OR], 2.61; 95% CI, 1.58-4.30) of HPV-positive tumor status after adjustment for age at diagnosis, sex, and smoking status. The strength of the association was greater among patients with oropharyngeal SCC (OR, 11.70; 95% CI, 2.09-65.53) compared with those with oral cavity SCC (OR, 2.32; 95% CI, 0.65-8.27) and laryngeal SCC (OR, 3.89; 95% CI, 0.95-15.99). CONCLUSIONS: A history of chronic inflammatory disease in the oral cavity may be associated with tumor HPV status in patients with HNSCC. This association seems to be stronger among patients with oropharyngeal cancer compared with those who have oral cavity or laryngeal SCC.
Assuntos
Carcinoma de Células Escamosas/virologia , Papillomavirus Humano 16/isolamento & purificação , Neoplasias Orofaríngeas/virologia , Periodontite/virologia , Perda do Osso Alveolar , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Neoplasias Orofaríngeas/epidemiologia , Periodontite/diagnóstico por imagem , Periodontite/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Radiografia PanorâmicaRESUMO
Nutritional supplementation is now a multibillion-dollar industry, and about half of all US adults take supplements. Supplement use is fueled in part by the belief that nutritional supplements can ward off chronic disease, including cancer, although several expert committees and organizations have concluded that there is little to no scientific evidence that supplements reduce cancer risk. To the contrary, there is now evidence that high doses of some supplements increase cancer risk. Despite this evidence, marketing claims by the supplement industry continue to imply anticancer benefits. Insufficient government regulation of the marketing of dietary supplement products may continue to result in unsound advice to consumers. Both the scientific community and government regulators need to provide clear guidance to the public about the use of dietary supplements to lower cancer risk.
Assuntos
Suplementos Nutricionais , Neoplasias/induzido quimicamente , Neoplasias/prevenção & controle , Oligoelementos , Vitaminas , Antioxidantes/administração & dosagem , Compostos de Cálcio , Doença Crônica/prevenção & controle , Suplementos Nutricionais/efeitos adversos , Suplementos Nutricionais/normas , Suplementos Nutricionais/estatística & dados numéricos , Ácido Fólico/administração & dosagem , Humanos , Saúde Pública , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Segurança , Marketing Social , Estados Unidos , United States Food and Drug Administration , Complexo Vitamínico B , Vitamina DRESUMO
BACKGROUND: Coffee has been hypothesized to have pro- and anticarcinogenic properties, whereas tea may contain anticarcinogenic compounds. Studies assessing coffee intake and pancreatic cancer risk have yielded mixed results, whereas findings for tea intake have mostly been null. Sugar-sweetened carbonated soft drink (SSB) intake has been associated with higher circulating levels of insulin, which may promote carcinogenesis. Few prospective studies have examined SSB intake and pancreatic cancer risk; results have been heterogeneous. METHODS: In this pooled analysis from 14 prospective cohort studies, 2,185 incident pancreatic cancer cases were identified among 853,894 individuals during follow-up. Multivariate (MV) study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models and then pooled using a random-effects model. RESULTS: No statistically significant associations were observed between pancreatic cancer risk and intake of coffee (MVRR = 1.10; 95% CI, 0.81-1.48 comparing ≥900 to <0 g/d; 237g ≈ 8oz), tea (MVRR = 0.96; 95% CI, 0.78-1.16 comparing ≥400 to 0 g/d; 237g ≈ 8oz), or SSB (MVRR = 1.19; 95% CI, 0.98-1.46 comparing ≥250 to 0 g/d; 355g ≈ 12oz; P value, test for between-studies heterogeneity > 0.05). These associations were consistent across levels of sex, smoking status, and body mass index. When modeled as a continuous variable, a positive association was evident for SSB (MVRR = 1.06; 95% CI, 1.02-1.12). CONCLUSION AND IMPACT: Overall, no associations were observed for intakes of coffee or tea during adulthood and pancreatic cancer risk. Although we were only able to examine modest intake of SSB, there was a suggestive, modest positive association for risk of pancreatic cancer for intakes of SSB.
Assuntos
Carboidratos/administração & dosagem , Bebidas Gaseificadas/estatística & dados numéricos , Café , Neoplasias Pancreáticas/epidemiologia , Chá , Adulto , Estudos de Coortes , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
Antioxidants such as selenium, vitamin E and C and carotenoids have been hypothesized as chemopreventive agents for several cancers. In the current review, we evaluate the results of epidemiological and interventional studies and summarize current knowledge of the prevention potential of the antioxidants, specific to gastrointestinal cancers. While early studies based on animal models and cell lines showed promise for antioxidants as chemopreventive agents for several gastrointestinal cancers, results from epidemiological studies and randomized trials do not support this promise. One large randomized trial, conducted in a region with widespread nutritional deficiency, showed that antioxidant use may confer protection against gastrointestinal cancers. However, this result has not been replicated in other epidemiological studies or the 10 other randomized trials conducted in developed Western countries. Overall, currently there is no evidence that antioxidants are protective against gastrointestinal cancers in populations whose members are replete in antioxidant intake.
Assuntos
Anticarcinógenos/uso terapêutico , Antioxidantes/uso terapêutico , Suplementos Nutricionais , Neoplasias Gastrointestinais/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Selênio/uso terapêutico , Animais , Quimioprevenção , Dieta , Frutas , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/metabolismo , Humanos , Estado Nutricional , Resultado do Tratamento , VerdurasRESUMO
BACKGROUND: Epidemiological studies evaluating the association between folate intake and risk of pancreatic cancer have produced inconsistent results. The statistical power to examine this association has been limited in previous studies partly because of small sample size and limited range of folate intake in some studies. METHODS: We analyzed primary data from 14 prospective cohort studies that included 319,716 men and 542,948 women to assess the association between folate intake and risk of pancreatic cancer. Folate intake was assessed through a validated food-frequency questionnaire at baseline in each study. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random effects model. All statistical tests were two-sided. RESULTS: During 7-20 years of follow-up across studies, 2195 pancreatic cancers were identified. No association was observed between folate intake and risk of pancreatic cancer in men and women (highest vs lowest quintile: dietary folate intake, pooled multivariable RR = 1.06, 95% CI = 0.90 to 1.25, P(trend) = .47; total folate intake [dietary folate and supplemental folic acid], pooled multivariable RR = 0.96, 95% CI = 0.80 to 1.16, P(trend) = .90). No between-study heterogeneity was observed (for dietary folate, P(heterogeneity) = .15; for total folate, P(heterogeneity) = .22). CONCLUSION: Folate intake was not associated with overall risk of pancreatic cancer in this large pooled analysis.
Assuntos
Comportamento Alimentar , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Neoplasias Pancreáticas/prevenção & controle , Estudos de Coortes , Fatores de Confusão Epidemiológicos , Feminino , Seguimentos , Humanos , Masculino , Análise Multivariada , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Inquéritos e QuestionáriosRESUMO
The threat of prostate cancer and the significant and often negative impact of its treatment underscore the importance of prevention. High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a potential premalignant lesion marking an increased risk of prostate cancer and substantial evidence suggests that men with HGPIN are in need of prostate cancer prevention. In vitro, in vivo, epidemiologic, and clinical trial evidence that selenium supplementation protects against prostate cancer motivated the study we report here: a double-blind, randomized, placebo-controlled trial of selenium 200 (µg/d) as selenomethionine in men with HGPIN. The primary endpoint was progression of HGPIN to prostate cancer over a 3-year period. This National Cancer Institute Intergroup trial was coordinated by the Southwest Oncology Group (SWOG). Of 619 enrolled patients, 423 randomized men with HGPIN (212 selenium and 211 placebo) were eligible (by central pathology review) and included in the primary analysis. Three-year cancer rates were 36.6% (placebo) versus 35.6% (selenium; P = 0.73, adjusted). The majority of patients who developed cancer on trial (70.8%, selenium and 75.5%, placebo) had a Gleason score of 6 or less than 6; there were no differences in Gleason scores between the two arms. Subset analyses included the finding of a nonsignificantly reduced prostate cancer risk (relative risk = 0.82; 95% CI: 0.40-1.69) in selenium versus placebo patients in the lowest quartile of baseline plasma selenium level (<106 ng/mL). Overall, and in all other subsets defined by baseline blood selenium levels, selenium supplementation had no effect on prostate cancer risk. The 36% prostate cancer rate in men with HGPIN indicates the association of this lesion with an elevated prostate cancer risk. Future study in this setting should focus on selenium-deficient populations and selenium pharmacogenetics.
Assuntos
Antioxidantes/uso terapêutico , Neoplasia Prostática Intraepitelial/patologia , Neoplasia Prostática Intraepitelial/prevenção & controle , Neoplasias da Próstata/patologia , Neoplasias da Próstata/prevenção & controle , Selênio/uso terapêutico , Idoso , Suplementos Nutricionais , Progressão da Doença , Método Duplo-Cego , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/sangue , Resultado do TratamentoRESUMO
Low folate status increases colorectal cancer risk. Paradoxically, overly abundant folate supplementation, which is not uncommon in the United States, may increase risk. The mechanisms of these effects are unknown. We conducted two translational studies to define molecular pathways in the human colon altered either by folate supplementation or by dietary folate depletion (followed by repletion). In the first study, 10 healthy, at-risk volunteers (with documented stable/normal folate intake) received supplemental folic acid (1 mg/d) for 8 weeks. In the second study, 10 similar subjects were admitted to a hospital as inpatients for 12 weeks to study folate depletion induced by a low folate diet. A repletion regimen of folic acid (1 mg/d) was provided for the last 4 of these weeks. Both studies included an 8-week run-in period to ensure stabilized folate levels prior to intervention. We obtained 12 rectosigmoid biopsies (from 4 quadrants of normal-appearing mucosa 10-15 cm from the anal verge) at baseline and at measured intervals in both studies for assessing the primary endpoints: genome-wide gene expression, genomic DNA methylation, promoter methylation (depletion/repletion study only), and p53 DNA strand breaks. Serum and rectosigmoid folate concentrations accurately tracked all changes in folate delivery (P < 0.05). In the first study, gene array analysis revealed that supplementation upregulated multiple inflammation- and immune-related pathways in addition to altering several 1-carbon-related enzymes (P < 0.001). In the second study, folate depletion downregulated genes involved in immune response, inflammation, the cell cycle, and mitochondrial/energy pathways; repletion reversed most of these changes. However, changes in gene expression after repletion in the second study (involving immune response and inflammation) did not reach the levels seen after supplementation in the first study. Neither genomic nor promoter-specific DNA methylation changed during the course of the depletion/repletion protocol, and genomic methylation did not change with supplementation in the first study. p53 DNA strand breaks increased with depletion after 12 weeks. In sum, depletion downregulates, whereas repletion or supplementation upregulates pathways related to inflammation and immune response. These findings provide novel support to the concept that excessive folate supplementation might promote colorectal carcinogenesis by enhancing proinflammatory and immune response pathways. These results indicate that modest changes in folate delivery create substantial changes in the molecular milieu of the human colon.
Assuntos
Transformação Celular Neoplásica/efeitos dos fármacos , Colo/efeitos dos fármacos , Deficiência de Ácido Fólico/metabolismo , Ácido Fólico/efeitos adversos , Reto/efeitos dos fármacos , Adulto , Idoso , Disponibilidade Biológica , Transformação Celular Neoplásica/metabolismo , Colo/metabolismo , Neoplasias Colorretais/etiologia , Quebras de DNA , Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais/efeitos adversos , Feminino , Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/genética , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Regiões Promotoras Genéticas/efeitos dos fármacos , Reto/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Supressora de Tumor p53/efeitos dos fármacos , Proteína Supressora de Tumor p53/genéticaRESUMO
OBJECTIVE: To evaluate the associations between intakes of vitamins A, C, and E and risk of colon cancer. METHODS: Using the primary data from 13 cohort studies, we estimated study- and sex-specific relative risks (RR) with Cox proportional hazards models and subsequently pooled RRs using a random effects model. RESULTS: Among 676,141 men and women, 5,454 colon cancer cases were identified (7-20 years of follow-up across studies). Vitamin A, C, and E intakes from food only were not associated with colon cancer risk. For intakes from food and supplements (total), the pooled multivariate RRs (95% CI) were 0.88 (0.76-1.02, >4,000 vs. ≤ 1,000 µg/day) for vitamin A, 0.81 (0.71-0.92, >600 vs. ≤ 100 mg/day) for vitamin C, and 0.78 (0.66-0.92, > 200 vs. ≤ 6 mg/day) for vitamin E. Adjustment for total folate intake attenuated these associations, but the inverse associations with vitamins C and E remained significant. Multivitamin use was significantly inversely associated with colon cancer risk (RR = 0.88, 95% CI: 0.81-0.96). CONCLUSIONS: Modest inverse associations with vitamin C and E intakes may be due to high correlations with folate intake, which had a similar inverse association with colon cancer. An inverse association with multivitamin use, a major source of folate and other vitamins, deserves further study.
Assuntos
Neoplasias do Colo/epidemiologia , Neoplasias do Colo/prevenção & controle , Vitaminas/administração & dosagem , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/farmacologia , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias do Colo/etiologia , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Europa (Continente)/epidemiologia , Feminino , Ácido Fólico/administração & dosagem , Seguimentos , Humanos , Incidência , Masculino , Análise Multivariada , América do Norte/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Medição de Risco , Vitamina A/administração & dosagem , Vitamina A/farmacologia , Vitamina E/administração & dosagem , Vitamina E/farmacologia , Vitaminas/farmacologiaRESUMO
BACKGROUND: The relationships between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk remain unresolved. METHODS: We investigated prospectively the association between coffee, tea, and sugar-sweetened carbonated soft drink consumption and colon cancer risk in a pooled analysis of primary data from 13 cohort studies. Among 731 441 participants followed for up to 6-20 years, 5604 incident colon cancer case patients were identified. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models and then pooled using a random-effects model. All statistical tests were two-sided. RESULTS: Compared with nonconsumers, the pooled multivariable relative risks were 1.07 (95% CI = 0.89 to 1.30, P(trend) = .68) for coffee consumption greater than 1400 g/d (about six 8-oz cups) and 1.28 (95% CI = 1.02 to 1.61, P(trend) = .01) for tea consumption greater than 900 g/d (about four 8-oz cups). For sugar-sweetened carbonated soft drink consumption, the pooled multivariable relative risk comparing consumption greater than 550 g/d (about 18 oz) to nonconsumers was 0.94 (95% CI = 0.66 to 1.32, P(trend) = .91). No statistically significant between-studies heterogeneity was observed for the highest category of each beverage consumed (P > .20). The observed associations did not differ by sex, smoking status, alcohol consumption, body mass index, physical activity, or tumor site (P > .05). CONCLUSIONS: Drinking coffee or sugar-sweetened carbonated soft drinks was not associated with colon cancer risk. However, a modest positive association with higher tea consumption is possible and requires further study.
Assuntos
Bebidas Gaseificadas/efeitos adversos , Café/efeitos adversos , Neoplasias do Colo/etiologia , Sacarose Alimentar/efeitos adversos , Comportamento Alimentar , Chá/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Neoplasias do Colo/prevenção & controle , Fatores de Confusão Epidemiológicos , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , América do Norte , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Edulcorantes/efeitos adversosRESUMO
PURPOSE OF REVIEW: In spite of improvements in care of colon cancer patients, prevention may enable potential patients to avoid cancer therapy. Although screening is direct and effective, dietary modification or low-risk chemopreventive agents might prevent colon cancer development. In this article, we review recent developments in colon cancer prevention, emphasizing nutrition. RECENT FINDINGS: Epidemiologic findings continue to suggest that diet is related to colon cancer risk. These findings, although, are inconsistent enough to render dietary recommendations premature. An exciting recent discovery is that the combination of diflouromethylornithine and sulindac substantially decreases adenomatous polyp recurrence. Reliance upon clinical trials continues to grow as a means of testing prevention strategies. SUMMARY: Prevention remains an important goal for reducing the burden of colon cancer. Screening has an important role, although it will probably not eliminate all colon cancer. Nutritional modification remains potentially valuable, although research has not yet identified the objects of nutritional intervention. NSAIDs hold promise as chemopreventive agents.
Assuntos
Anticarcinógenos/uso terapêutico , Neoplasias do Colo/prevenção & controle , Dieta , Fenômenos Fisiológicos da Nutrição , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Fibras na Dieta/uso terapêutico , Eflornitina/uso terapêutico , Estudos Epidemiológicos , Humanos , Prevenção Primária , Fatores de Risco , Fumar/efeitos adversos , Sulindaco/uso terapêuticoRESUMO
Nonexperimental studies suggest that individuals with higher selenium (Se) status are at decreased risk of cancer. The Nutritional Prevention of Cancer (NPC) study randomized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo; selenium supplementation decreased the risk of lung, colon, prostate, and total cancers but increased the risk of nonmelanoma skin cancer. In this article, we report on a small substudy in Macon, GA, which began in 1989 and randomized 424 patients to 400-mcg/day of Se or to matched placebo. The subjects from both arms had similar baseline Se levels to those treated by 200 mcg, and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg. The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25%; however, 400-mcg/day of Se had no effect on total cancer incidence.
Assuntos
Anticarcinógenos/administração & dosagem , Estado Nutricional , Selênio/administração & dosagem , Selênio/sangue , Neoplasias Cutâneas/prevenção & controle , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Cutâneas/epidemiologiaRESUMO
Observational epidemiology and experimentation by randomized controlled trials (RCTs) have been used to evaluate dietary factors in cancer prevention; however, consistency in findings has been elusive. In several circles, RCTs are viewed as more credible than observational studies. As the testing of dietary epidemiological findings in RCTs has been more common for colorectal cancer than for other cancers, we use experience with this malignancy to critically appraise the reasons for discrepancies between results of observational and experimental studies.
Assuntos
Neoplasias Colorretais/prevenção & controle , Dieta , Pesquisa Empírica , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Neoplasias Colorretais/dietoterapia , Suplementos Nutricionais , Ácido Fólico/sangue , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodosRESUMO
BACKGROUND: Findings from animal models suggest that selenium supplementation improves glucose metabolism. OBJECTIVE: To examine the effect of long-term selenium supplementation on the incidence of type 2 diabetes. DESIGN: Secondary analysis of a randomized, double-blind, placebo-controlled trial. SETTING: Areas of low selenium consumption of the eastern United States. PATIENTS: 1202 persons seen in dermatology clinics who did not have type 2 diabetes at baseline. INTERVENTION: Oral administration of selenium, 200 microg/d, or placebo. MEASUREMENTS: Incidence of type 2 diabetes. RESULTS: During an average follow-up of 7.7 years (SD, 2.7), type 2 diabetes developed in 58 selenium recipients and 39 placebo recipients (incidence, 12.6 cases per 1000 person-years vs. 8.4 cases per 1000 person-years, respectively; hazard ratio, 1.55 [95% CI, 1.03 to 2.33]). The lack of benefit of selenium supplementation on the incidence of type 2 diabetes persisted in analyses stratified by age, sex, body mass index, and smoking status. An exposure-response gradient was found across tertiles of baseline plasma selenium level, with a statistically significantly increased risk for type 2 diabetes in the highest tertile of baseline plasma selenium level (hazard ratio, 2.70 [CI, 1.30 to 5.61]). LIMITATIONS: Diabetes was a secondary outcome in the parent trial. Diagnoses of diabetes were self-reported but were validated in most participants. The sample was mostly older and white. CONCLUSIONS: Selenium supplementation does not seem to prevent type 2 diabetes, and it may increase risk for the disease. Click here for related information on selenium.
Assuntos
Antioxidantes/administração & dosagem , Diabetes Mellitus Tipo 2/prevenção & controle , Suplementos Nutricionais , Selênio/administração & dosagem , Idoso , Antioxidantes/efeitos adversos , Antioxidantes/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Selênio/efeitos adversos , Selênio/sangue , Fatores de Tempo , Estados UnidosRESUMO
Specific beverage intake may be associated with the risk of renal cell cancer through a diluting effect of carcinogens, alterations of hormone levels, or other changes in the renal tubular environment, but few prospective studies have examined these associations. We evaluated the associations between coffee, tea, milk, soda and fruit and vegetable juice intakes and renal cell cancer risk in a pooled analysis of 13 prospective studies (530,469 women and 244,483 men). Participants completed a validated food-frequency questionnaire at baseline. Using the primary data, the study-specific relative risks (RRs) were calculated and then pooled using a random effects model. A total of 1,478 incident renal cell cancer cases were identified during a follow-up of 7-20 years across studies. Coffee consumption was associated with a modestly lower risk of renal cell cancer (pooled multivariate RR for 3 or more 8 oz (237 ml) cups/day versus less than one 8 oz (237 ml) cup/day = 0.84; 95% CI = 0.67-1.05; p value, test for trend = 0.22). Tea consumption was also inversely associated with renal cell cancer risk (pooled multivariate RR for 1 or more 8 oz (237 ml) cups/day versus nondrinkers = 0.85; 95% CI = 0.71-1.02; pvalue, test for trend = 0.04). No clear associations were observed for milk, soda or juice. Our findings provide strong evidence that neither coffee nor tea consumption increases renal cell cancer risk. Instead, greater consumption of coffee and tea may be associated with a lower risk of renal cell cancer. (c) 2007 Wiley-Liss, Inc.
Assuntos
Bebidas , Carcinoma de Células Renais/epidemiologia , Inquéritos sobre Dietas , Animais , Bebidas Gaseificadas , Café , Feminino , Humanos , Masculino , Leite , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Chá , Fatores de TempoRESUMO
The phenomenon of losing statistical significance with increasing follow-up can arise when a proportional hazard model is applied in a clinical trial where the impact of the intervention results in delaying a negative event such as cancer diagnosis, progression or death. Often parametric methods can be employed in such a setting, however, in studies where only a small percentage of subjects have an event, these methods are often inappropriate. We present an alternative method based on a weighted Kaplan-Meier estimator and a permutation test, and demonstrate its utility in the setting of the Nutritional Prevention of Cancer study where increasing follow-up resulted in loss of statistical significance for the ability of selenized yeast to prevent lung cancer.