Stephanie L. Barrera

Dietary zinc, copper and selenium, and risk of lung cancer

Zinc, copper and selenium are important cofactors for several enzymes that play a role in maintaining DNA integrity. However, limited epidemiologic research on these dietary trace metals and lung cancer risk is available. In an ongoing study of 1,676 incident lung cancer cases and 1,676 matched healthy controls, we studied the associations between dietary zinc, copper and selenium and lung cancer risk. Using multiple logistic regression analysis, the odds ratios (OR) and 95% confidence intervals (CI) of lung cancer for all subjects by increasing quartiles of dietary zinc intake were 1.0, 0.80 (0.65–0.99), 0.64 (0.51–0.81), 0.57 (0.42–0.75), respectively (p trend = 0.0004); similar results were found for men. For dietary copper, the ORs and 95% CI for all subjects were 1.0, 0.59 (0.49–0.73), 0.51 (0.41–0.64), 0.34 (0.26–0.45), respectively (p trend < 0.0001); similar reductions in risk and trend were observed by gender. Dietary selenium intake was not associated with risk, except for a significant inverse trend (p = 0.04) in men. Protective trends (p < 0.05) against lung cancer with increased dietary zinc intake were also found for all ages, BMI > 25, current smokers, pack‐years ≤30, light drinkers and participants without emphysema. Increased dietary copper intake was associated with protective trends (p < 0.05) across all ages, BMI, smoking and vitamin/mineral supplement categories, pack‐years ≤30 and 30.1–51.75 and participants without emphysema. Our results suggest that dietary zinc and copper intakes are associated with reduced risk of lung cancer. Given the known limitations of case–control studies, these findings must be interpreted with caution and warrant further investigation.

Saturated fat intake predicts biochemical failure after prostatectomy

Previous reports show that obesity predicts biochemical failure after treatment for localized prostate cancer. Since obesity is associated with increased fat consumption, we investigated the role that dietary fat intake plays in modulating obesity‐related risk of biochemical failure. We evaluated the association between saturated fat intake and biochemical failure among 390 men from a previously described prostatectomy cohort. Participants completed a food frequency questionnaire collecting nutrient information for the year prior to diagnosis. Because fat and energy intake are highly correlated, the residual method was used to adjust fat (total and saturated) intakes for energy. Biochemical‐failure‐free‐survival rates were calculated using the Kaplan–Meier method. Crude and adjusted effects were estimated using Cox proportional hazards models. During a mean follow‐up of 70.6 months, 78 men experienced biochemical failure. Men who consumed high‐ saturated fat (HSF) diets were more likely to experience biochemical failure (p = 0.006) and had significantly shorter biochemical‐failure‐free‐survival than men with low saturated fat (LSF) diets (26.6 vs. 44.7 months, respectively, p = 0.002). After adjusting for obesity and clinical variables, HSF‐diet patients were almost twice as likely to experience biochemical failure (hazard ratio = 1.95, p = 0.008) compared to LSF diet patients. Men who were both obese and consumed HSF diets had the shortest biochemical‐failure‐free‐survival (19 months), and nonobese men who consumed LSF diets had the longest biochemical‐failure‐free‐survival (46 months, p < 0.001). Understanding the interplay between modifiable factors, such as diet and obesity, and disease characteristics may lead to the development of behavioral and/or targeted interventions for patients at increased risk of progression.

Dietary Boron and Hormone Replacement Therapy as Risk Factors for Lung Cancer in Women

Hormone replacement therapy (HRT) may reduce lung cancer risk. Dietary boron may have actions similar to those of HRT; however, no previous study has reported the associations between dietary boron intake and lung cancer risk or the joint effects of boron intake and HRT use on lung cancer risk. The authors examined the associations between boron intake and the joint effects of boron intake and HRT on lung cancer risk in women. In an ongoing case-control study in Houston, Texas (July 1995 through April 2005, end date for this analysis), 763 women were diagnosed with lung cancer, and 838 were matched healthy controls with data on both diet and HRT. Multiple logistic regression analyses were conducted to assess the associations between dietary boron and HRT with lung cancer risk. After adjustment for potential confounders, the odds ratios for lung cancer with decreasing quartiles of dietary boron intake were 1.0, 1.39 (95% confidence interval (CI): 1.02, 1.90), 1.64 (95% CI: 1.20, 2.24), and 1.95 (95% CI: 1.42, 2.68) mg/day, respectively, for all women (p(trend) < 0.0001). In joint-effects analyses, compared with women with high dietary boron intake who used HRT, the odds ratio for lung cancer for low dietary boron intake and no HRT use was 2.07 (95% CI: 1.53, 2.81). Boron intake was inversely associated with lung cancer in women, whereas women who consumed low boron and did not use HRT were at substantial increased odds.

Dietary magnesium and DNA repair capacity as risk factors for lung cancer

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.

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.

CYberinfrastructure for COmparative effectiveness REsearch (CYCORE): improving data from cancer clinical trials

ABSTRACTImproved approaches and methodologies are needed to conduct comparative effectiveness research (CER) in oncology. While cancer therapies continue to emerge at a rapid pace, the review, synthesis, and dissemination of evidence-based interventions across clinical trials lag in comparison. Rigorous and systematic testing of competing therapies has been clouded by age-old problems: poor patient adherence, inability to objectively measure the environmental influences on health, lack of knowledge about patients’ lifestyle behaviors that may affect cancer’s progression and recurrence, and limited ability to compile and interpret the wide range of variables that must be considered in the cancer treatment. This lack of data integration limits the potential for patients and clinicians to engage in fully informed decision-making regarding cancer prevention, treatment, and survivorship care, and the translation of research results into mainstream medical care. Particularly important, as noted in a 2009 report on CER to the President and Congress, the limited focus on health behavior-change interventions was a major hindrance in this research landscape (DHHS 2009). This paper describes an initiative to improve CER for cancer by addressing several of these limitations. The Cyberinfrastructure for Comparative Effectiveness Research (CYCORE) project, informed by the National Science Foundation’s 2007 report “Cyberinfrastructure Vision for 21st Century Discovery” has, as its central aim, the creation of a prototype for a user-friendly, open-source cyberinfrastructure (CI) that supports acquisition, storage, visualization, analysis, and sharing of data important for cancer-related CER. Although still under development, the process of gathering requirements for CYCORE has revealed new ways in which CI design can significantly improve the collection and analysis of a wide variety of data types, and has resulted in new and important partnerships among cancer researchers engaged in advancing health-related CI.

N-Nitroso Compounds: Assessing Agreement between Food Frequency Questionnaires and 7-Day Food Records

BACKGROUND N-nitroso compounds are recognized as important dietary carcinogens. Accurate assessment of N-nitroso intake is fundamental to advancing research regarding its role with cancer. Previous studies have not used a quantitative database to estimate the intake of these compounds in a US population. OBJECTIVE To address this gap, a database of N-nitroso values was developed in conjunction with an existing food frequency questionnaire (FFQ). In this article we report on the relative validity of the FFQ instrument modified to estimate intake of N-nitroso compounds. DESIGN Intake estimates of 23 N-nitroso compounds from the FFQ were compared with those from 7-day food records in a cross-sectional study conducted from January 2005 through June 2006. SUBJECTS A sample of 98 healthy adult subjects (aged 50.42+/-12.84 years) completed an FFQ and then recorded foods and beverages consumed on 7-day food records. RESULTS Crude and energy-adjusted N-nitroso compounds intakes were significantly higher in the FFQ than the 7-day food records (P<0.001). Spearman correlations for crude and energy-adjusted N-nitroso intakes ranged from 0.004 to 0.48. By tertiles of N-nitiroso compounds, there was moderate agreement (kappa>0.30) for five compounds. Higher estimates of N-nitroso compounds by FFQ was explained by a greater proportion of subjects who reported eating foods high in N-nitroso compounds on FFQ than reported on 7-day food records. CONCLUSION The modified FFQ with N-nitroso values is a useful tool for assessing N-nitroso intakes relative to a group, and captures all food items with N-nitroso compounds, including those foods with high concentrations and eaten sporadically.

Extant health behaviors and uptake of standardized vs tailored health messages among cancer survivors enrolled in the FRESH START trial: a comparison of fighting-spirits vs fatalists

Objective: Cancer coping styles have been associated with several cancer‐related outcomes. We examined whether baseline lifestyle behaviors differed between cancer survivors with fatalistic vs fighting‐spirit coping styles, and whether there was differential response to two diet‐exercise mailed‐print interventions, one standardized and another individually tailored.

Abstract B109: Tea and coffee consumption, DNA repair, and lung cancer risk

Tea, the major source of flavonol in the U.S. diet, has demonstrated chemopreventive capacity in animal and in vitro research. We examined the associations between tea/coffee and lung cancer risk by specific type of and preparation method of the beverage, stage and histology as well as the joint effect of DNA repair capacity (DRC) and beverage on cancer risk. In a case‐control study conducted by the Department of Epidemiology of the University of Texas M. D. Anderson Cancer Center, 1,088 lung cancer patients were recruited along with 1,127 controls who were frequency matched to cases by age (± 5 y), gender, ethnicity and smoking status (never, former, current). Using logistic regression analysis to adjust for recognized covariates including smoking status and pack‐years smoked, the odds ratios (OR) for lung cancer among individuals who drank more than a cup/week of the following were: OR =0.44; 95% CI = 0.31–0.64 for green tea; OR = 0.64; 95% CI = 0.45–0.90 for decaffeinated black tea, when compared with non‐drinkers and those who drank less than a cup a week of other beverages. In contrast, those who drank more than 3 cups/day of regular coffee had a 30% higher odds of lung cancer (OR = 1.30; 95% CI = 1.01–1.09). No association was found for regular black tea and decaffeinated coffee consumption. Similar findings appeared by stage and among adenocarcinomas and squamous cell cancers of the lung. When drinkers of other tea/coffee beverages were excluded from each model, all findings remained significant except for regular coffee. Compared to green tea drinkers who were proficient in DRC or not proficient, green tea drinkers had an almost threefold higher OR of lung cancer. In conclusion, we report the potential chemopreventive effects of drinking more than a cup a week of green tea and decaffeinated black tea on lung cancer. Our findings need replication in a prospective analysis Citation Information: Cancer Prev Res 2010;3(1 Suppl):B109.

Abstract CN09-03: Capitalizing on the teachable moment of the cancer diagnosis to promote healthful lifestyle changes among women with breast cancer and their daughters: Preliminary findings of the DAMES Trial

Introduction: Excessive body weight, as reflected by a body mass index [BMI (kg/m 2 ) > 25] is consistently and independently associated, not only with post‐menopausal breast cancer incidence, but mortality as well, with weight gain during adulthood being most strongly associated with risk. In addition, there is consensus that an increased BMI at the time of diagnosis is a poor prognostic indicator, and accumulating evidence that weight gain post‐diagnosis is associated with poorer overall and disease‐free survival. Thus, to reduce the burden of breast cancer, efforts are needed to promote weight control and to target those most at risk, i.e., women who already have breast cancer (for tertiary prevention of progressive/ recurrent disease and co‐morbidity) and their 1 st degree relatives (as a means of primary prevention). Previous studies also suggest that the cancer diagnosis catalyzes a “teachable moment” that may provide an opportune time for health promotion. The DAMES trial (Daughters And MothErS against breast cancer) is currently in the field and will explore whether the momentum of the teachable moment created by the cancer diagnosis, as well as the mother‐daughter bond, can be harnessed and used to promote weight loss in overweight women with breast cancer and their overweight adult daughters, and to discern whether team‐based vs. independently‐delivered interventions offer more promise. Methods: 68 women diagnosed with loco‐regional breast cancer within 5‐years and their adult daughters (body mass index [BMI] 25+) were randomized to: 1) a tailored diet‐exercise intervention emphasizing the mother‐daughter team (TEAM); 2) a tailored diet‐exercise intervention delivered to mothers and daughters independently (INDEPENDENT); or 3) an attention control arm that received standardized diet‐exercise materials in the public domain (CONTROL); the unit of randomization was the motherdaughter dyad and the distribution of dyads was as follows: 25 dyads in the TEAM; 25 dyads in the INDEPENDENT, and 18 dyads in the CONTROL arms. All interventions consisted of mailed print materials (personalized workbook, plus 6 mailings over the course of the 1‐year study period. TEAM & INDEPENDENT participants also received pedometers, portion control tableware, diet/exercise logs, and iPoDs during the intervention (the control arm received iPoDs upon completion of the study). In addition to monitoring accrual, retention and adverse events, effect sizes (variation) regarding changes in weight status and lifestyle behaviors were assessed at baseline, 6‐and 12‐month follow‐up. Survey data (e.g., dietary intake of energy, saturated fat, fruits and vegetables and nutrient density via 2‐day dietary recalls, level of physical activity via the Godin Leisure Time Physical Activity Questionnaire [with supporting accelerometry], social support, in general and specific to changing diet and exercise via the Duke Social Support Index and the Sallis et al. Social Support Index for Diet and Exercise, Stage of Readiness and Self‐Efficacy for diet and exercise change, perceived risk of recurrence [for mothers] and primary risk of breast cancer [for daughters], health‐related quality of life via the SF‐36, and strength of the mother‐daughter bond via the Interpersonal Closeness Score) were captured at each time point via computer‐assisted telephone interviews, and anthropometric measures (weight, height, waist circumference and blood pressure) were assessed inperson by study staff. Results: While this study is still in the field, at present the full sample has been accrued and randomized; characteristics of the study sample are as follows: Race/Ethnicity (73%White, 18%African American, 7% Hispanic and 2% Asian); Mean Years of Age (Mothers: 61/Daughters: 36), and Mean Distance Separating Dyad Members: 75 miles). It is noteworthy that although this study was able to achieve its accrual target, a substantial number of breast cancer cases (N=2336) were contacted in order fulfill enrollment. While only a 26% response rate was achieved for the initial screener which accompanied the letter of invitation, the leading reasons for women reporting that they could not participate was because they either did not have an adult‐aged daughter, or did not have a daughter who was overweight. At the time of this abstract submission, data collection is almost complete for the 6‐month time point. At this time, attrition is minimal (3%) and only two serious adverse events have been reported (none of which is attributable to the intervention). Preliminary findings from 57 dyads suggest that both the TEAM and INDEPENDENT interventions were associated with significant changes from baseline with decreases in mean dyadic weight (sd) over time being −6.44 (7.49) kg and −6.90 (8.91) kg, respectively as compared to the control −1.61 (6.0) kg (p‐values Conclusions: The mother‐daughter weight loss interventions appear feasible as indicated by full enrollment, excellent acceptance, low attrition, and the absence of serious attributable adverse events. Thus far, the lessons learned from this study are as follows: 1) Substantial numbers of women with breast cancer are not eligible on the basis that they don9t have a daughter, or one who is interested and eligible; 2) Preliminary data suggest that both interventions perform better than the control; however, data appear somewhat stronger (though not significantly) for mothers assigned to the TEAM intervention, whereas daughters appear to perform better with the INDEPENDENT intervention; and 3) More complete data will be available in the upcoming months to provide some clues as to the effects of the interventions over the longer term (1‐year), and will include dietary data, as well as analyses that explore potential moderation by the mother‐daughter bond. These additional data will be important in determining the future of family‐based lifestyle interventions aimed at the prevalent problem of breast cancer, and for developing future interventions that harness the momentum of the teachable moment and that optimize existing relationships and family dynamics to promote healthful lifestyle change. Citation Information: Cancer Prev Res 2010;3(1 Suppl):CN09-03.