Marian L. Neuhouser

Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients

PURPOSE Chronic inflammation is believed to contribute to the development and progression of breast cancer. Systemic C-reactive protein (CRP) and serum amyloid A (SAA) are measures of low-grade chronic inflammation and potential predictors of cancer survival. PATIENTS AND METHODS We evaluated the relationship between circulating markers of inflammation and breast cancer survival using data from the Health, Eating, Activity, and Lifestyle (HEAL) Study (a multiethnic prospective cohort study of women diagnosed with stage 0 to IIIA breast cancer). Circulating concentrations of CRP and SAA were measured approximately 31 months after diagnosis and tested for associations with disease-free survival (approximately 4.1 years of follow-up) and overall survival (approximately 6.9 years of follow-up) in 734 disease-free breast cancer survivors. Cox proportional hazards models were used with adjustment for potential confounding factors to generate hazard ratios (HRs) and 95% CIs. Results Elevated SAA and CRP were associated with reduced overall survival, regardless of adjustment for age, tumor stage, race, and body mass index (SAA P trend < .0001; CRP P trend = .002). The HRs for SAA and CRP tertiles suggested a threshold effect on survival, rather than a dose-response relationship (highest v lowest tertile: SAA HR = 3.15; 95% CI, 1.73 to 5.65; CRP HR = 2.27; 95% CI, 1.27 to 4.08). Associations were similar and still significant after adjusting for self-reported history of cardiovascular events and censoring cardiovascular disease deaths. Elevated CRP and SAA were also associated with reduced disease-free survival, although these associations were of borderline significance (SAA P trend = .04; CRP P trend = .07). CONCLUSION Circulating SAA and CRP may be important prognostic markers for long-term survival in breast cancer patients, independent of race, tumor stage, and body mass index.

Dietary Flavonoids and Cancer Risk: Evidence From Human Population Studies

Abstract: High dietary intake of fruits and vegetables is consistently associated with a reduced risk of common human cancers, including cancers of the lung, breast, prostate, and colon. It is unknown which bioactive compound or compounds in plant foods provide the chemoprotective effects. One class of compounds currently under investigation is flavonoids, a large group of compounds with similar structure, consisting of two phenolic benzene rings linked to a heterocyclic pyran or pyrone. Although there are numerous in vitro and animal model data suggesting that flavonoids influence important cellular and molecular mechanisms related to carcinogenesis, such as cell cycle control and apoptosis, there are limited data from human population studies. This article reviews data from four cohort studies and six case-control studies, which have examined associations of flavonoid intake with cancer risk. There is consistent evidence from these studies that flavonoids, especially quercetin, may reduce the risk of lung cancer. Further research using new dietary databases for food flavonoid content is needed to confirm these findings before specific public health recommendations about flavonoids can be formulated.

Use Of Food Nutrition Labels is Associated with Lower Fat Intake

OBJECTIVE The Nutrition Labeling and Education Act of 1990 mandated that standardized nutrition information appear on almost all packaged foods manufactured after May 1994. This study describes the demographic and diet-related psychosocial correlates of nutrition label use, and examines the relationship between label use and diet. DESIGN/SUBJECTS Data are from a random-digit-dial telephone survey of 1,450 adult residents of Washington State. The questionnaire assessed nutrition label use, fat-related diet habits, fruit and vegetable consumption, diet-related psychosocial factors, health behavior, and demographic characteristics. STATISTICAL ANALYSES Analyses examined associations of demographic characteristics with nutrition label use; diet-related psychosocial factors and health behavior with nutrition label use, controlled for demographic characteristics; and nutrition label use with fat and fruit and vegetable intake, controlled for demographic characteristics and psychosocial factors. RESULTS Nutrition label use was significantly higher among women, residents younger than 35 years, and residents with more than a high school education. When controlled for demographic characteristics, the strongest predictors of label use were believing in the importance of eating a low-fat diet, believing in an association between diet and cancer, and being in the maintenance stage of change for adopting a low-fat diet. Label use was significantly associated with lower fat intake and, after controlling for all demographic, psychosocial, and behavioral variables, explained 6% of the variance in fat intake (P < .001). Label use was not associated with fruit and vegetable consumption. APPLICATIONS/CONCLUSION Persons successfully limiting their fat intake use nutrition labels, suggesting that the new nutrition labels are helpful. Dietetics professionals can use the results of this study to emphasize to their clients the importance of reading nutrition labels in maintaining a low-fat diet.

Obesity, diabetes, and risk of prostate cancer: Results from the prostate cancer prevention trial

Studies on the relationship between obesity and prostate cancer incidence are inconsistent. In part, this inconsistency may be due to a differential effect of obesity on low-grade and high-grade cancer or confounding of the association of obesity with prostate cancer risk by diabetes. We investigated the associations of obesity and diabetes with low-grade and high-grade prostate cancer risk. Data were from 10,258 participants (1,936 prostate cancers) in the Prostate Cancer Prevention Trial who all had cancer presence or absence determined by prostate biopsy. Multiple logistic regression was used to model the risk of total prostate cancer, and polytomous logistic regression was used to model the risk of low-grade and high-grade prostate cancer. Compared with men with body mass index < 25, obese men (body mass index ≥30) had an 18% [odds ratio (OR), 0.82; 95% confidence interval (95% CI), 0.69-0.98] decreased risk of low-grade prostate cancer (Gleason <7) and a 29% (OR, 1.29; 95% CI, 1.01-1.67) increased risk of high-grade prostate cancer (Gleason ≥7) or, alternatively, a 78% (OR, 1.78; 95% CI, 1.10-2.87) increased risk defining high-grade cancer as Gleason sum 8 to 10. Diabetes was associated with a 47% (OR, 0.53; 95% CI, 0.34-0.83) reduced risk of low-grade prostate cancer and a 28% (OR, 0.72; 95% CI, 0.55-0.94) reduced risk of high-grade prostate cancer. Associations of obesity or diabetes with cancer risk were not substantially changed by mutually statistical controlling for each other. Obesity increases the risk of high-grade but decreases the risk of low-grade prostate cancer, and this relationship is independent of the lower risk for prostate cancer among men with diabetes. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1977–83)

Use of Recovery Biomarkers to Calibrate Nutrient Consumption Self-Reports in the Women's Health Initiative

Underreporting of energy consumption by self-report is well-recognized, but previous studies using recovery biomarkers have not been sufficiently large to establish whether participant characteristics predict misreporting. In 2004-2005, 544 participants in the Womens Health Initiative Dietary Modification Trial completed a doubly labeled water protocol (energy biomarker), 24-hour urine collection (protein biomarker), and self-reports of diet (assessed by food frequency questionnaire (FFQ)), exercise, and lifestyle habits; 111 women repeated all procedures after 6 months. Using linear regression, the authors estimated associations of participant characteristics with misreporting, defined as the extent to which the log ratio (self-reported FFQ/nutritional biomarker) was less than zero. Intervention women in the trial underreported energy intake by 32% (vs. 27% in the comparison arm) and protein intake by 15% (vs. 10%). Younger women had more underreporting of energy (p = 0.02) and protein (p = 0.001), while increasing body mass index predicted increased underreporting of energy and overreporting of percentage of energy derived from protein (p = 0.001 and p = 0.004, respectively). Blacks and Hispanics underreported more than did Caucasians. Correlations of initial measures with repeat measures (n = 111) were 0.72, 0.70, 0.46, and 0.64 for biomarker energy, FFQ energy, biomarker protein, and FFQ protein, respectively. Recovery biomarker data were used in regression equations to calibrate self-reports; the potential application of these equations to disease risk modeling is presented. The authors confirm the existence of systematic bias in dietary self-reports and provide methods of correcting for measurement error.

Addressing Current Criticism Regarding the Value of Self-Report Dietary Data

Recent reports have asserted that, because of energy underreporting, dietary self-report data suffer from measurement error so great that findings that rely on them are of no value. This commentary considers the amassed evidence that shows that self-report dietary intake data can successfully be used to inform dietary guidance and public health policy. Topics discussed include what is known and what can be done about the measurement error inherent in data collected by using self-report dietary assessment instruments and the extent and magnitude of underreporting energy compared with other nutrients and food groups. Also discussed is the overall impact of energy underreporting on dietary surveillance and nutritional epidemiology. In conclusion, 7 specific recommendations for collecting, analyzing, and interpreting self-report dietary data are provided: (1) continue to collect self-report dietary intake data because they contain valuable, rich, and critical information about foods and beverages consumed by populations that can be used to inform nutrition policy and assess diet-disease associations; (2) do not use self-reported energy intake as a measure of true energy intake; (3) do use self-reported energy intake for energy adjustment of other self-reported dietary constituents to improve risk estimation in studies of diet-health associations; (4) acknowledge the limitations of self-report dietary data and analyze and interpret them appropriately; (5) design studies and conduct analyses that allow adjustment for measurement error; (6) design new epidemiologic studies to collect dietary data from both short-term (recalls or food records) and long-term (food-frequency questionnaires) instruments on the entire study population to allow for maximizing the strengths of each instrument; and (7) continue to develop, evaluate, and further expand methods of dietary assessment, including dietary biomarkers and methods using new technologies.

Types of Alternative Medicine Used by Patients with Breast, Colon, or Prostate Cancer: Predictors, Motives, and Costs

OBJECTIVE Assess predictors and costs of various types of alternative medicine used by adult patients with cancer. DESIGN, LOCATION, SUBJECTS: Telephone survey of 356 patients with colon, breast, or prostate cancer identified from the population-based Cancer Surveillance System of western Washington. RESULTS Overall, 70.2% of patients used at least one type of alternative medicine, with 16.6% seeing alternative providers, 19.1% using mental/other therapy, and 64.6% taking dietary supplements. Compared to males, females were five times more likely to see an alternative provider and about twice as likely to use mental therapies or supplements (p < 0.05 for all). Older patients were less likely to use mental/other therapy. Higher education (but not income) was associated with use of all types of alternative medicine. Patients with multiple medical treatments were two times more likely to take dietary supplements compared to patients having only surgery (p < 0.01). Varying by the type of alternative therapy, 83%-97% of patients reported that they used alternative medicine for general health and well-being while 8% to 56% reported use for treatment of cancer. Almost all patients reported that the alternative therapy improved their well-being. Expenditures for alternative medicine averaged

Protein intake and incident frailty in the Women's Health Initiative observational study.

68 per user per year, but ranged from

Pooled Results From 5 Validation Studies of Dietary Self-Report Instruments Using Recovery Biomarkers for Energy and Protein Intake

4 to

Multivitamin use and risk of cancer and cardiovascular disease in the women's health initiative cohorts

14,659. CONCLUSIONS Given the high prevalence of use and that patients believed that alternative medicine improved their well-being, clinicians should show an open mind toward these treatment choices and encourage frank discussion. Familiarity and some knowledge regarding use of alternative medicine is important in cases where interactions between conventional and alternative medicine may occur. It is also important to identify potential patient needs for mental health support beyond conventional care and support patients who want to make healthful lifestyle changes. Longitudinal investigations are urgently needed to investigate associations of alternative medicine use with survival and quality of life in patients with cancer.