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Biomedical subjects

Meir Stampfer

Publications and source records attributed to Meir Stampfer.

10 recordsLinked to original sources

Vitamin and mineral supplements for cancer prevention: issues and evidence.

Trials of nutritional supplements for cancer prevention must overcome a variety of challenges not shared in the usual paradigm of pharmaceutical agents for prevention of cardiovascular disease. Unlike for cardiovascular disease, for cancer we typically do not have well-established causal risk factors as targets for intervention. Also, for most likely cancer interventions, the expected time to achieve an effect is much longer, more variable, and far less well understood than for cardiovascular disease, and the progression of pathophysiology is much harder-or impossible-to follow, in contrast with imaging for progression of atherosclerosis in cardiovascular disease. Also, cancers at various sites have a wide range of etiologies. The optimal age for intervention, best dose, and duration needed to test nutritional agents for cancer prevention are largely unknown, making null findings hard to interpret. Unlike with drugs, baseline nutritional status can be critical. Moreover, because the nutritional agents are often readily available, adherence in control groups in trials can be impaired. Several gene-nutrient and nutrient-nutrient interactions have been identified that could affect trial results. Some studies suggest that particular nutrients may be effective only in subgroups defined by genotypes or by nutritional status of another nutrient. All these challenges must be considered in planning informative trials. Long-term prospective cohort studies, especially with repeated measures and high follow-up, can provide useful data for planning trials as well as the basis for rational recommendations while awaiting trial results or in settings where trials may be infeasible.

Dietary Supplements↗

Intake of fruits and vegetables, carotenoids, folate, and vitamins A, C, E and risk of bladder cancer among women (United States).

OBJECTIVE: To examine the relation between fruits and vegetables, carotenoids, folate, and vitamins A, C, E and the risk of bladder cancer in a prospective study of women. METHODS: A total of 237 incident bladder cancer cases were documented during 20 years of follow-up among 88,796 women enrolled in the Nurses' Health Study. Dietary intake was assessed by food-frequency questionnaires every two to four years and incident diagnosis of bladder cancer was ascertained every two years. Cox proportional hazard models were used to estimate incidence rate ratios (RR) and 95% confidence intervals (CI) for bladder cancer risk, adjusting for age, pack-years of smoking, current smoking, and total caloric intake. RESULTS: Consumption of total fruits and vegetables was not associated with bladder cancer risk (RR = 1.08, 95% CI = 0.70-1.65, for > 5.5 compared to < 2.5 servings per day). Similarly, dietary intakes of carotenoids, folate, and vitamins A, C, E, were not related to bladder cancer risk. No association was observed between supplemental intake of multivitamins, vitamins A, C, E and bladder cancer risk. CONCLUSIONS: We did not observe any association for fruit and vegetable consumption or vitamin intake and bladder cancer risk among women.

Adult↗

Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial.

CONTEXT: In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials. OBJECTIVE: To determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins. DESIGN: Double-blind randomized controlled trial (September 1996-May 2003). SETTING AND PARTICIPANTS: 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland. INTERVENTIONS: All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration's reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 microg of pyridoxine, 6 microg of cobalamin and 20 microg of folic acid. MAIN OUTCOME MEASURES: Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes). RESULTS: Mean reduction of total homocysteine was 2 micromol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9.2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P =.80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3- micromol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P =.05), a 26% lower risk of CHD events (P<.001), and a 16% lower risk of death (P =.001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death. CONCLUSIONS: In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary.

Adult↗

The association between gout and nephrolithiasis in men: The Health Professionals' Follow-Up Study.

Approximately 10 million adults in the United States have experienced the passage of a kidney stone, and up to 5 million have been diagnosed with gout by a physician. Previous reports have suggested that gout increases the risk for the development of kidney stones, but there are no prospective data. We used data from a cohort of 51,529 male health care professionals to examine the independent association between gout and kidney stone disease. In a cross-sectional analysis of gout and kidney stone disease reported on the 1986 baseline questionnaire, the prevalence of kidney stone disease was almost twofold higher in men with history of gout compared to those without (15% vs. 8%). After adjusting for age and body mass index (BMI), a history of gout remained significantly associated with kidney stone disease (OR 1.88; 95% CI 1.68 to 2.11). We then prospectively examined the risk of incident kidney stones in men with and without a confirmed diagnosis of gout after excluding men who reported a history of kidney stone disease or gout on the baseline questionnaire. A confirmed diagnosis of gout increased the multivariate relative risk of incident kidney stones (RR 2.12; 95% CI 1.22 to 3.68). In contrast, a history of kidney stone disease was not associated with increased risk of gout (RR 1.05; 95% CI 0.54 to 2.07). In conclusion, a history of gout independently increases the risk for incident kidney stones in men. Physicians should provide dietary counseling, such as increasing fluid intake and decreasing salt consumption, to subjects with gout in addition to other risk factors, such as family history of kidney stones, in order to decrease the likelihood of stone formation.

Adult↗

Associations between carcinogen-DNA damage, glutathione S-transferase genotypes, and risk of lung cancer in the prospective Physicians' Health Cohort Study.

DNA damage from polycyclic aromatic hydrocarbons (PAH) and other aromatic/hydrophobic compounds has been implicated in case-control studies as a risk factor for lung cancer, as have common polymorphisms in the glutathione S-transferase (GST) genes involved in carcinogen detoxification. However, their joint effects have not been evaluated in prospective studies, leaving open questions about predictive value of these biomarkers. In this matched case-control study nested within the prospective Physicians' Health Study, we evaluated whether biomarkers measured in white blood cells (WBC) significantly predicted risk, alone and in combination, after controlling for level of smoking. The biomarkers reported here are aromatic/hydrophobic-DNA adducts and polymorphisms in genes coding for the GSTM1 and GSTP1 enzymes. Our study population was composed of 89 cases of primary lung cancer and 173 controls, matched in a 1:2 ratio on smoking, age and duration of follow up. Adducts were measured in WBC DNA by the nuclease P1-enhanced (32)P-post-labeling method. Genotypes (GSTM1 null versus non-null and GSTP1 Val versus GSTP1 Ile) were determined by genomic amplification and restriction fragment length polymorphism analysis. Among current smokers, adducts were significant predictors of lung cancer risk (after adjusting for GST genotypes, OR = 3.10, 95% CI 1.07, 9.01). The combined GSTM1 null/GSTP1 Val genotype was associated with lung cancer overall and especially among former smokers, before and after adjusting for adducts (OR for former smokers = 4.21, CI 1.08, 16.41; adjusted OR = 4.68, CI 1.17, 18.71). Among cases only, adducts were significantly higher among current or former smokers with the GSTM1 non-null/GSTP1 Ile genotype. The two risk factors (adducts and genotypes) appear to be independent predictors of risk. The findings underscore the complex and important role of biological susceptibility as a determinant of risk from carcinogens found in tobacco smoke and other environmental compounds.

Biomarkers↗