Jacqueline M. Major

Urinary Biomarkers of Meat Consumption

Background: Meat intake has been positively associated with incidence and mortality of chronic diseases, including diabetes, heart disease, and several different cancers, in observational studies by using self-report methods of dietary assessment; however, these dietary assessment methods are subject to measurement error. One method to circumvent such errors is the use of biomarkers of dietary intake, but currently there are no accepted biomarkers for meat intake. Methods: We investigated four analytes (creatinine, taurine, 1-methylhistidine, and 3-methylhistidine) specifically found in meat and excreted in urine. Twenty-four–hour urine samples were collected from 17 individuals on controlled diets containing varying levels of meat: vegetarian (0 g/d), low red meat (60 g/d), medium red meat (120 g/d), and high red meat (420 g/d), as part of two randomized crossover feeding studies. Results: When compared with the low red meat diet or the vegetarian diet, the urinary levels of all four analytes were significantly higher in urine samples collected after 15 days of a high red meat diet (P < 0.0001). Only urinary 1-methylhistidine and 3-methylhistidine were statistically significantly different for every diet type, increasing as the amount of meat in the diet increased (P < 0.01 for 1-methylhistidine and P < 0.05 for 3-methylhistidine). Furthermore, urinary excretion of 1-methylhistidine and 3-methylhistidine elevated with increasing meat intake in every individual. Conclusion: Urinary 1-methylhistidine and 3-methylhistidine may be good biomarkers of meat intake. Impact: To determine the public health impact of red meat on cancer risk, biomarkers are crucial to estimate true intake; these potential biomarkers should be further investigated in free-living populations. Cancer Epidemiol Biomarkers Prev; 20(6); 1107–11. ©2011 AACR.

Socioeconomic status and the risk of colorectal cancer: an analysis of more than a half million adults in the National Institutes of Health-AARP Diet and Health Study.

No previous prospective US study has examined whether the incidence of colorectal cancer (CRC) is disproportionately high in low socioeconomic status (SES) populations of both men and women. This study examined the relationship between both individual and area‐level SES and CRC incidence, overall and by tumor location.

Health status, neighborhood socioeconomic context, and premature mortality in the United States: The National Institutes of Health-AARP Diet and Health Study.

OBJECTIVES We examined whether the risk of premature mortality associated with living in socioeconomically deprived neighborhoods varies according to the health status of individuals. METHODS Community-dwelling adults (n = 566,402; age = 50-71 years) in 6 US states and 2 metropolitan areas participated in the ongoing prospective National Institutes of Health-AARP Diet and Health Study, which began in 1995. We used baseline data for 565,679 participants on health behaviors, self-rated health status, and medical history, collected by mailed questionnaires. Participants were linked to 2000 census data for an index of census tract socioeconomic deprivation. The main outcome was all-cause mortality ascertained through 2006. RESULTS In adjusted survival analyses of persons in good-to-excellent health at baseline, risk of mortality increased with increasing levels of census tract socioeconomic deprivation. Neighborhood socioeconomic mortality disparities among persons in fair-to-poor health were not statistically significant after adjustment for demographic characteristics, educational achievement, lifestyle, and medical conditions. CONCLUSIONS Neighborhood socioeconomic inequalities lead to large disparities in risk of premature mortality among healthy US adults but not among those in poor health.

Insulin-Like Growth Factor-I and Cancer Mortality in Older Men

CONTEXT Although numerous studies have explored the relation of IGF-I with cancer incidence, few have investigated the association between IGF-I and cancer mortality. OBJECTIVE This study examined the association of serum IGF-I levels with cancer mortality in older community-dwelling men. DESIGN, SETTING, AND PARTICIPANTS We conducted a prospective, population-based study of 633 men aged 50 yr and older (mean = 73) who attended a 1988-1991 research clinic visit when blood was obtained for measurement of IGF-I. Participants were followed for vital status through July 2006. MAIN OUTCOME MEASURE All-cancer mortality was assessed. RESULTS Median IGF-I was 96 ng/ml. During the 18-yr follow-up, 368 deaths occurred; 74 (20%) were due to cancer. Cox regression analyses showed a significant quadratic association between IGF-I and all-cancer mortality (P = 0.039). Higher levels of IGF-I were associated with progressively higher risk of cancer death after adjusting for age, IGF-binding protein-1, adiposity, exercise, current smoking, and previous cancer. The adjusted risk of cancer death was statistically significant for IGF-I levels above 120 ng/ml, with magnitudes of effect ranging from 1.61 [95% confidence interval (CI) = 1.28-2.02] to 2.61 (95% CI = 1.46-4.64). For the 46% of men with IGF-I above 100 ng/ml, the risk of fatal cancer was 1.82 (95% CI = 1.11-2.96) compared to the risk with lower levels. CONCLUSIONS Higher serum IGF-I in older men is associated with increased risk of cancer death, independent of age, adiposity, lifestyle, and cancer history. These results suggest caution in the use of IGF-I-enhancing therapies to slow the adverse effects of aging.

Geographic Variation in Colorectal Cancer Survival and the Role of Small-Area Socioeconomic Deprivation: A Multilevel Survival Analysis of the NIH-AARP Diet and Health Study Cohort

Adverse socioeconomic conditions, at both the individual and the neighborhood level, increase the risk of colorectal cancer (CRC) death, but little is known regarding whether CRC survival varies geographically and the extent to which area-level socioeconomic deprivation affects this geographic variation. Using data from the National Institutes of Health (NIH)-AARP Diet and Health Study, the authors examined geographic variation and the role of area-level socioeconomic deprivation in CRC survival. CRC cases (n = 7,024), identified during 1995-2003, were followed for their CRC-specific vital status through 2005 and overall vital status through 2006. Bayesian multilevel survival models showed that there was significant geographic variation in overall (variance = 0.2, 95% confidence interval (CI): 0.1, 0.2) and CRC-specific (variance = 0.3, 95% CI: 0.1, 0.4) risk of death. More socioeconomically deprived neighborhoods had a higher overall risk of death (most deprived quartile vs. least deprived: hazard ratio = 1.2, 95% CI: 1.1, 1.4) and a higher CRC-specific risk of death (most deprived quartile vs. least deprived: hazard ratio = 1.2, 95% CI: 1.1, 1.5). However, neighborhood socioeconomic deprivation did not account for the geographic variation in overall and CRC-specific risks of death. In future studies, investigators should evaluate other neighborhood characteristics to help explain geographic heterogeneity in CRC survival. Such research could facilitate interventions for reducing geographic disparity in CRC survival.

A prospective analysis of telomere length and pancreatic cancer in the alpha-tocopherol beta-carotene cancer (ATBC) prevention study

Smoking and diabetes, consistent risk factors for pancreatic cancer, are also factors that influence telomere length maintenance. To test whether telomere length is associated with pancreatic cancer risk, we conducted a nested case–control study in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50–69 years at baseline. Between 1992 and 2004, 193 incident cases of pancreatic adenocarcinoma occurred (mean follow‐up from blood draw: 6.3 years) among participants with whole blood samples available for telomere length assays. For these cases and 660 controls, we calculated odds ratios (OR) and 95% confidence intervals using unconditional logistic regression, adjusting for age, number of years smoked regularly, and history of diabetes mellitus. Telomere length was categorized into quartiles (shortest to longest) and analyzed as both a categorical and a continuous normal variable (reported per 0.2 unit increase in telomere length). All statistical tests were two‐sided. Longer telomere length was significantly associated with increased pancreatic cancer risk (continuous OR = 1.26 95% CI = 1.09–1.46; highest quartile compared to lowest, OR = 1.57, 95% CI = 1.01–2.43, p‐trend = 0.007). This association remained for subjects diagnosed within the first five years of blood draw (continuous OR = 1.46, 95% CI = 1.19–1.79 highest quartile OR = 2.92, 95% CI = 1.47–5.77, p‐trend = 0.002), but not those diagnosed greater than five years after blood draw (continuous OR = 1.03, 95% CI = 0.85–1.22; highest quartile OR = 1.04, 95% CI = 0.60–1.79). This is the first prospective study to suggest an association between longer blood leukocyte telomere length and increased pancreatic cancer risk.

Variability and Reproducibility of Circulating Vitamin D in a Nationwide U.S. Population

CONTEXT Most studies examining associations between circulating vitamin D and disease are based on a single measure of vitamin D, which may not reflect levels over time, particularly because vitamin D concentrations vary by season. Few studies evaluated how well multiple 25-hydroxyvitamin D [25(OH)D] measures track within the same individual over time. OBJECTIVE This study examined variability and reproducibility of vitamin D by evaluating repeat measurements of plasma 25(OH)D concentrations while accounting for determinants of circulating concentrations including dietary supplement use and latitude of residence from a population of U.S. radiologic technologists. DESIGN AND PARTICIPANTS We analyzed circulating 25(OH)D in blood samples taken from 538 men and women from a prospective, nationwide study at two time points within a 1-yr period, most measured in different seasons. Inter- and intra-individual variability, reliability coefficients, and measurement error were examined. RESULTS The spearman rank correlation between two measurements of 25(OH)D concentrations was moderate (r = 0.75, P < 0.001) and did not vary significantly by participant characteristics including age, race, or latitude. The intraclass correlation coefficient was 0.72 (95% confidence interval = 0.68-0.76). The deattenuation factor of plasma 25(OH)D levels was 1.39, suggesting that a single measure of vitamin D on a continuous scale in regression analyses may result in attenuated relationships of about 40%. CONCLUSION Our results suggest that a single blood sample obtained in spring or fall provides a reasonable average for 25(OH)D over a 1-yr period, but additional studies are needed to estimate variability and agreement in plasma 25(OH)D measurements over longer intervals and younger populations.

Potential Attenuation of Disease Progression in Recurrent Prostate Cancer With Plant-Based Diet and Stress Reduction:

A rising level of prostate-specific antigen (PSA), after primary surgery or radiation therapy, is the hallmark of recurrent prostate cancer and is often the earliest sign of extraprostatic spread in patients who are otherwise asymptomatic. While hormonal therapy may slightly extend survival in a minority of patients, it is not curative and produces side effects including hot flashes, decreased libido, and loss of bone mass. Alternatively, dietary modification may offer an important tool for clinical management. Epidemiologic studies have associated the Western diet not only with prostate cancer incidence but also with a greater risk of disease progression after treatment. Conversely, many elements of plant-based diets have been associated with reduced risk of progression. However, dietary modification can be stressful and difficult to implement. We therefore conducted a 6-month pilot clinical trial to investigate whether adoption of a plant-based diet, reinforced by stress management training, could attenuate the rate of further PSA rise. Urologists at the University of California, San Diego, and San Diego Veterans Affairs Medical Centers recruited 14 patients with recurrent prostate cancer. A pre-post design was employed in which each patient served as his own control. Rates of PSA rise were ascertained for each patient for the following periods: from the time of posttreatment recurrence up to the start of the study (prestudy) and from the time immediately preceding the intervention (baseline) to the end of the intervention (0-6 months). There was a significant decrease in the rate of PSA rise from prestudy to 0 to 6 months ( P < .01). Four of 10 evaluable patients experienced an absolute reduction in their PSA levels over the entire 6-month study. Nine of 10 had a reduction in their rates of PSA rise and an improvement of their PSA doubling times. Median PSA doubling time increased from 11.9 months (prestudy) to 112.3 months (intervention). These results provide preliminary evidence that adoption of a plant-based diet, in combination with stress reduction, may attenuate disease progression and have therapeutic potential for clinical management of recurrent prostate cancer.

Coping strategies, hostility, and depressive symptoms: A path model

Previous studies of coping, hostility, and depressive symptoms have highlighted the significant relations between all possible pairs of these 3 variables. To more completely explore the nature of depressive symptoms, we link them all together in this study by testing a coping→hostility→depressive symptoms path model.One hundred forty participants completed psychological questionnaires measuring coping strategies, hostility, and depressive symptoms. While controlling age and social class as covariates, SPSS stepwise regression analyses were used to examine relations among these 3 constructs.Results suggest that coping has a direct relation with depressive symptoms as well as an indirect relation mediated by hostility. Passive coping may lead to increased hostility, resulting in depressive symptoms. Active coping may have the opposite effect.These findings suggest that the inclusion of measures of both coping strategies and hostility yields a more thorough understanding of concomitants of depressive symptoms. From a clinical perspective, knowing what coping strategies a person uses and how much anger they experience and express may be useful in guiding the management of depressive symptoms.

Genome-Wide Association Study Identifies Three Common Variants Associated with Serologic Response to Vitamin E Supplementation in Men

Vitamin E inhibits lipid peroxidation in cell membranes, prevents oxidative damage to DNA by scavenging free radicals, and reduces carcinogen production. No study to our knowledge, however, has examined the association between genetic variants and response to long-term vitamin E supplementation. We conducted a genome-wide association study (GWAS) of common variants associated with circulating α-tocopherol concentrations following 3 y of controlled supplementation. The study population included 2112 middle-aged, male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort who received a trial supplementation of α-tocopherol (50 mg/d) and had fasting serum α-tocopherol concentrations measured after 3 y. Serum concentrations were log-transformed for statistical analysis and general linear models adjusted for age, BMI, serum total cholesterol, and cancer case status. Associations with serum response to α-tocopherol supplementation achieved genome-wide significance for 2 single nucleotide polymorphisms (SNP): rs964184 on 11q23.3 (P = 2.6 × 10(-12)) and rs2108622 on 19pter-p13.11 (P = 2.2 × 10(-7)), and approached genome-wide significance for one SNP, rs7834588 on 8q12.3 (P = 6.2 × 10(-7)). Combined, these SNP explain 3.4% of the residual variance in serum α-tocopherol concentrations during controlled vitamin E supplementation. A GWAS has identified 3 genetic variants at different loci that appear associated with serum concentrations after vitamin E supplementation in men. Identifying genetic variants that influence serum nutrient biochemical status (e.g., α-tocopherol) under supplementation conditions improves our understanding of the biological determinants of these nutritional exposures and their associations with cancer etiology.