Search tips
Search criteria

Results 1-10 (10)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Association Between Diet During Preadolescence and Adolescence and Risk for Breast Cancer During Adulthood 
That diet during pre-adolescence and adolescence has important consequences for breast cancer during adulthood is increasingly evident. However, only a few epidemiologic studies have been conducted of the relationship between diet during pre-adolescence and adolescence and cancer during adulthood. This situation is partly due to methodological challenges such as the long latency period, the complexity of breast cancer, lack of validated diet assessment tools, and the large number of subjects that must be followed, all of which increase costs. In addition, funding opportunities are few for such studies. Results from the small number of epidemiologic studies are inconsistent, but evidence is emerging that specific aspects of the diet during pre-adolescence and adolescence are important. For example, during pre-adolescence and adolescence, severe calorie restriction with poor food quality, high total fat intake, and alcohol intake tend to increase risk, whereas high soy intake decreases risk. Research on pre-adolescent and adolescent diet is a paradigm shift in breast cancer investigations. This research paradigm has the potential to produce transformative knowledge to inform breast cancer prevention strategies through dietary intervention during pre-adolescence and adolescence, rather than later in life, as is current practice, when it is perhaps less effective. Methodological challenges that have plagued the field might now be overcome by leveraging several existing large-scale cohort studies in the United States and around the world to investigate the role of diet during pre-adolescence and adolescence in risk for adult breast cancer.
PMCID: PMC3622736  PMID: 23298994
Pre-adolescent diet; Adolescent diet; Adult breast cancer
2.  Dietary α-, β-, γ- and δ-tocopherols in lung cancer risk 
Studies of vitamin E and cancer have focused on the α-tocopherol form of the vitamin. However, other forms of vitamin E, in particular γ-tocopherol may have unique mechanistic characteristics relevant to lung cancer prevention. In an ongoing study of 1,088 incident lung cancer cases and 1,414 healthy matched controls, we studied the associations between 4 tocopherols (α-, β-, γ-, and δ-tocopherol) in the diet and lung cancer risk. Using multiple logistic regression analysis, the adjusted odds ratios (OR) and 95% confidence intervals (CI) of lung cancer for increasing quartiles of dietary α-tocopherol intake were 1.0, 0.63 (0.50–0.79), 0.58 (0.44–0.76) and 0.39 (0.28–0.53), respectively (p-trend < 0.0001). For dietary intake of β-tocopherol, the OR and 95% CI for all subjects were: 1.0, 0.79 (0.63–0.98), 0.59 (0.45–0.78) and 0.56 (0.42–0.74), respectively (p-trend < 0.0001). Similar results for dietary γ-tocopherol intake were observed: 1.0, 0.84 (0.67–1.06), 0.76 (0.59–0.97) and 0.56 (0.42–0.75), respectively (p- trend = 0.0002). No significant association between δ-tocopherol intake and lung cancer risk was detected. When the 4 tocopherols were summed as total tocopherol intake, a monotonic risk reduction was also observed. When we entered the other tocopherols in our model, only the association with dietary α-tocopherol intake remained significant; i.e., increasing intake of dietary α-tocopherol accounted for 34–53% reductions in lung cancer risk. To the best of our knowledge, this is the first report of the independent associations of the 4 forms of dietary tocopherol (α-, β-, γ- and δ-tocohperol) on lung cancer risk. Given the limitations with case-control studies, these findings need to be confirmed in further investigations.
PMCID: PMC3380426  PMID: 18546288
dietary tocopherols; lung cancer risk; diet and lung cancer; vitamin E and lung cancer
3.  Epigenetic Contributions to the Relationship between Cancer and Dietary Intake of Nutrients, Bioactive Food Components, and Environmental Toxicants 
Epigenetics is the study of heritable changes in gene expression that occur without a change in DNA sequence. Cancer is a multistep process derived from combinational crosstalk between genetic alterations and epigenetic influences through various environmental factors. The observation that epigenetic changes are reversible makes them an attractive target for cancer prevention. Until recently, there have been difficulties studying epigenetic mechanisms in interactions between dietary factors and environmental toxicants. The development of the field of cancer epigenetics during the past decade has been advanced rapidly by genome-wide technologies – which initially employed microarrays but increasingly are using high-throughput sequencing – which helped to improve the quality of the analysis, increase the capacity of sample throughput, and reduce the cost of assays. It is particularly true for applications of cancer epigenetics in epidemiologic studies that examine the relationship among diet, epigenetics, and cancer because of the issues of tissue heterogeneity, the often limiting amount of DNA samples, and the significant cost of the analyses. This review offers an overview of the state of the science in nutrition, environmental toxicants, epigenetics, and cancer to stimulate further exploration of this important and developing area of science. Additional epidemiologic research is needed to clarify the relationship between these complex epigenetic mechanisms and cancer.
PMCID: PMC3266615  PMID: 22303385
cancer; epigenetics; diet; nutrient; toxicants
4.  Measures of adiposity and body fat distribution in relation to serum folate levels in postmenopausal women in a feeding study 
To assess the associations between serum folate concentration and measures of adiposity in postmenopausal women.
This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n=51) consumed 0g (control), 15g (one drink), and 30g (two drinks) alcohol (ethanol)/d for 8 weeks as part of a controlled diet. Subjects in one treatment arm were crossed-over to another arm after a two to five week washout period. BMI was measured, and dual energy x-ray absorptiometry (DEXA) scan administered to the women during the control (0 g alcohol) treatment, and a blood sample from this group was collected at baseline and week 8 of each diet period and analyzed for folate, B12, homocysteine, and methylmalonic acid.
This study was conducted at the Beltsville Human Nutrition Research Center, Maryland, USA.
In multivariate analysis, women who were overweight had a 12% lower, and obese women had a 22% lower serum folate concentrations compared to normal weight women (P-trend=0.02). Vitamin B12 also decreased with increasing BMI (P-trend=0.08). Increased BMI, percent body fat, and absolute amounts of central and peripheral fat were all significantly associated with decreased serum folate, but were unrelated to serum B12, homocysteine, or methylmalonic acid.
Our data show that adiposity is associated with lower serum folate levels in postmenopausal women. With obesity at epidemic proportions, these data, if confirmed by prospective or randomized controlled studies, have important public health implications.
This research was supported in part by the Intramural Program of the NIH.
Adiposity and folate
PMCID: PMC3236439  PMID: 17457338
Adiposity and folate; postmenopausal women; feeding study
5.  Mineral intake and lung cancer risk in the NIH-AARP Diet and Health Study 
Using data from a case-control study, we previously reported that low dietary intakes of magnesium (Mg), iron (Fe), zinc (Zn), copper (Cu), but not selenium (Se) and calcium (Ca) were associated with increased lung cancer risk. Due to dietary recall bias in case-control studies our objective was to assess whether these findings hold in a prospective cohort study.
We analyzed data from the NIH-AARP Diet and Health study of 482,875 subjects (288,257 men and 194,618 women) who were cancer-free and completed a food frequency questionnaire (FFQ) at enrollment between 1995 and 2003. Cox proportional hazards models were computed to estimate the relative risk (RR) adjusted for potential confounders.
During a mean follow-up of 7 years, 7,052 lung cancer cases were identified. For all subjects, we observed no significant associations between total (diet + supplement) Ca, Mg, Fe, Cu, Se, and Zn intakes and lung cancer risk. Total Ca intake was protective (P-trend<0.05) for current smokers and subjects with adenocarcinomas. Total Mg intake increased risk (P-trend<0.05) in men and current smokers. Total Fe intake was inversely associated with risk in women (P-trend<0.01). For dietary minerals, Mg increased risk (P-trend<0.05) in all subjects, among men and current smokers. Increased dietary Ca intake reduced risk in women (P-trend=0.05). Dietary Fe decreased risk in all subjects and among women (P-trend<0.05). Mineral intake from supplements did not affect lung cancer risk.
Dietary mineral consumption may influence lung cancer risk, but the associations differ by type of mineral and population subgroups.
PMCID: PMC2921219  PMID: 20696660
Diet; minerals; lung cancer; smoking
6.  Pooling Dietary Data Using Questionnaires With Open-ended and Predefined Responses: Implications for Comparing Mean Intake or Estimating Odds Ratios 
American Journal of Epidemiology  2010;171(6):682-690.
In the current era of diet-gene analyses, large sample sizes are required to uncover the etiology of complex diseases. As such, consortia form and often combine available data. Food frequency questionnaires, which commonly use 2 different types of responses about the frequency of intake (predefined responses and open-ended responses), may be pooled to achieve the desired sample size. The common practice is to categorize open-ended responses into the predefined response categories. A problem arises when the predefined categories are noncontiguous: possible open-ended responses may fall in gaps between the predefined categories. Using simulated data modeled from frequency of intake among 1,664 controls in a lung cancer case-control study at The University of Texas M. D. Anderson Cancer Center (Houston, Texas, 2000–2005), the authors describe the effect of different categories of open-ended responses that fall in between noncontiguous, predefined response sets on estimates of the mean difference in intake and the odds ratios. A significant inflation of false positives appears when comparing mean differences of intake, while the bias in estimating odds ratios may be acceptably small. Therefore, if pooling data cannot be restricted to the same type of response, inferences should focus on odds ratio estimation to minimize bias.
PMCID: PMC2842226  PMID: 20139126
computer simulation; data interpretation, statistical; diet surveys
7.  A prospective study of polymorphisms of DNA repair genes XRCC1, XPD23 and APE/ref‐1 and risk of stroke in Linxian, China 
Stroke is the leading cause of death in Linxian, China. Although there is evidence of DNA damage in experimental stroke, no data exist on DNA repair and stroke in human populations.
To assess the risk of stroke conferred by polymorphisms in the DNA repair genes, XRCC1, XPD23 and APE/ref‐1 in a cohort of individuals originally assembled as subjects in two cancer prevention trials in Linxian, China.
The subjects for this prospective study were sampled from a cohort of 4005 eligible subjects who were alive and cancer free in 1991 and had blood samples available for DNA extraction. Using real‐time Taqman analyses, all incident cases of stroke (n = 118) that developed from May 1996, and an age‐ and a sex‐stratified random sample (n = 454) drawn from all eligible subjects were genotyped. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% CIs.
No association was observed between polymorphisms in APE/ref‐1 codon 148 and XRCC1*6 codon 194, and stroke. Polymorphisms in XRCC1*10 codon 399 were associated with a significantly reduced risk of stroke (RR 0.59, 95% CI 0.36 to 0.96, p = 0.033), whereas XPD23 codon 312 was associated with a significantly increased risk of stroke (RR 2.18, 95% CI 1.14 to 4.17, p = 0.010).
Polymorphisms in DNA repair genes may be important in the aetiology of stroke. These data should stimulate research on DNA damage and repair in stroke.
PMCID: PMC2653006  PMID: 17630376
8.  Dietary magnesium and DNA repair capacity as risk factors for lung cancer 
Carcinogenesis  2008;29(5):949-956.
Magnesium (Mg) is required for maintenance of genomic stability; however, data on the relationship between dietary Mg intake and lung cancer are lacking. In an ongoing lung cancer case–control study, we identified 1139 cases and 1210 matched healthy controls with data on both diet and DNA repair capacity (DRC). Dietary intake was assessed using a modified Block-NCI food frequency questionnaire and DRC was measured using the host-cell reactivation assay to assess repair in lymphocyte cultures. After adjustment for potential confounding factors including DRC, the odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer with increasing quartiles of dietary Mg intake were 1.0, 0.83 (0.66–1.05), 0.64 (0.50–0.83) and 0.47 (0.36–0.61), respectively, for all subjects (P-trend < 0.0001). Similar results were observed by histology and clinical stage of lung cancer. Low dietary Mg intake was associated with poorer DRC and increased risk of lung cancer. In joint effects analyses, compared with those with high dietary Mg intake and proficient DRC, the OR (95% CI) for lung cancer in the presence of both low dietary Mg and suboptimal DRC was 2.36 (1.83–3.04). Similar results were observed for men and women. The effects were more pronounced among older subjects (>60 years), current or heavier smokers, drinkers, those with a family history of cancer in first-degree relatives, small cell lung cancer and late-stage disease. These intriguing results need to be confirmed in prospective studies.
PMCID: PMC2902380  PMID: 18448487
9.  Body Mass Index, percent body fat, and regional body fat distribution in relation to leptin concentrations in healthy, non-smoking postmenopausal women in a feeding study 
Nutrition Journal  2007;6:3.
The relationship between BMI and leptin has been studied extensively in the past, but previous reports in postmenopausal women have not been conducted under carefully controlled dietary conditions of weight maintenance using precise measures of body fat distribution. The aim of the present study was to examine the association between serum leptin concentration and adiposity as estimated by BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat, central and peripheral fat, and lean mass) in postmenopausal women.
This study was conducted as a cross-sectional analysis within the control segment of a randomized, crossover trial in which postmenopausal women (n = 51) consumed 0 (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks as part of a controlled diet. BMIs were determined and DEXA scans were administered to the women during the 0 g alcohol treatment, and a blood sample was collected at baseline and week 8 of each study period for leptin analysis.
Results and discussion
In multivariate analysis, women who were overweight (BMI > 25 to ≤ 30 kg/m2) had a 2-fold increase, and obese women (BMI > 30 kg/m2) had more than a 3-fold increase in serum leptin concentrations compared to normal weight (BMI ≤25 kg/m2) women. When the models for the different measures of adiposity were assessed by multiple R2, models which included percent body fat explained the highest proportion (approximately 80%) of the serum leptin variance.
Under carefully controlled dietary conditions, we confirm that higher levels of adiposity were associated with higher concentrations of serum leptin. It appears that percent body fat in postmenopausal women may be the best adiposity-related predictor of serum leptin.
PMCID: PMC1781463  PMID: 17229323
10.  The effects of moderate alcohol supplementation on estrone sulfate and DHEAS in postmenopausal women in a controlled feeding study 
Nutrition Journal  2004;3:11.
We have demonstrated that moderate alcohol consumption (15 g/d, 30 g/d) for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. We now report on the relationships between serum estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) levels after 4 weeks of moderate alcohol supplementation, and compare the results to the 8 weeks data to elucidate time-to-effect differences.
Postmenopausal women (n = 51) consumed 0 (placebo), 15 (1 drink), and 30 (2 drinks) g alcohol (ethanol)/ day for 8 weeks as part of a controlled diet in a randomized crossover design. Blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Changes in estrone sulfate and DHEAS levels from placebo to 15 g and 30 g alcohol per day were estimated using linear mixed models.
Results and Discussion
At week 4, compared to the placebo, estrone sulfate increased an average 6.9% (P = 0.24) when the women consumed 15 g of alcohol per day, and 22.2% (P = 0.0006) when they consumed 30 g alcohol per day. DHEAS concentrations also increased significantly by an average of 8.0% (P < 0.0001) on 15 g of alcohol per day and 9.2% (P < 0.0001) when 30 g alcohol was consumed per day. Trend tests across doses for both estrone sulfate (P = 0.0006) and DHEAS (P < 0.0001) were significant. We found no significant differences between the absolute levels of serum estrone sulfate at week 4 versus week 8 (P = 0.32) across all doses. However, absolute DHEAS levels increased from week 4 to week 8 (P < 0.0001) at all three dose levels.
These data indicate that the hormonal effects due to moderate alcohol consumption are seen early, within 4 weeks of initiation of ingestion.
PMCID: PMC517945  PMID: 15353002
Alcohol; Hormones; Postmenopausal women

Results 1-10 (10)