Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk.

BACKGROUND: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. METHODS: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. RESULTS: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. CONCLUSIONS: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. IMPACT: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

"We're Just Not Prepared for Eating Over Our Whole Life": A Mixed Methods Approach to Understanding Dietary Behaviors Among Longer Term Cancer Survivors.

BACKGROUND: In many countries, there are growing numbers of persons living with a prior diagnosis of cancer, due to the aging population and more successful strategies for treatment. There is also growing evidence of the importance of healthful diet and weight management for survivorship, yet many long-term cancer survivors are not successfully following recommendations. METHODS: We explored this issue in a mixed methods study with 53 adult survivors of 3 cancers (breast, prostate, and non-Hodgkin's lymphoma), living in Maryland. Participants provided three 24-hour dietary recalls, and results were used to classify respondents on 2 metrics of healthful eating (the Healthy Eating Index 2010, and a 9-item index based on current dietary recommendations). Recalls were also used to guide in-depth qualitative discussions with participants regarding self-assessment of dietary behaviors, healthful eating, and diet's importance in cancer prevention and survivorship. RESULTS: Survivors following a more healthful diet were more likely to be female, have greater socioeconomic resources, more years since diagnosis, normal weight, and no smoking history. Qualitative discussions revealed a more nuanced understanding of dietary strategies among healthful eaters, as well as the importance of household members in dietary decision making. DISCUSSION: Most survivors had received little nutrition counseling as part of their cancer care, highlighting the importance of holistic, household-oriented nutrition education for maintaining health among long-term cancer survivors.

Selenium and Prostate Cancer: Analysis of Individual Participant Data From Fifteen Prospective Studies.

BACKGROUND: Some observational studies suggest that a higher selenium status is associated with a lower risk of prostate cancer but have been generally too small to provide precise estimates of associations, particularly by disease stage and grade. METHODS: Collaborating investigators from 15 prospective studies provided individual-participant records (from predominantly men of white European ancestry) on blood or toenail selenium concentrations and prostate cancer risk. Odds ratios of prostate cancer by selenium concentration were estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. RESULTS: Blood selenium was not associated with the risk of total prostate cancer (multivariable-adjusted odds ratio [OR] per 80 percentile increase = 1.01, 95% confidence interval [CI] = 0.83 to 1.23, based on 4527 case patients and 6021 control subjects). However, there was heterogeneity by disease aggressiveness (ie, advanced stage and/or prostate cancer death, Pheterogeneity = .01), with high blood selenium associated with a lower risk of aggressive disease (OR = 0.43, 95% CI = 0.21 to 0.87) but not with nonaggressive disease. Nail selenium was inversely associated with total prostate cancer (OR = 0.29, 95% CI = 0.22 to 0.40, Ptrend < .001, based on 1970 case patients and 2086 control subjects), including both nonaggressive (OR = 0.33, 95% CI = 0.22 to 0.50) and aggressive disease (OR = 0.18, 95% CI = 0.11 to 0.31, Pheterogeneity = .08). CONCLUSIONS: Nail, but not blood, selenium concentration is inversely associated with risk of total prostate cancer, possibly because nails are a more reliable marker of long-term selenium exposure. Both blood and nail selenium concentrations are associated with a reduced risk of aggressive disease, which warrants further investigation.

Clinical care providers' perspectives on body size and weight management among long-term cancer survivors.

OBJECTIVE: To examine clinical care providers' perspectives on cancer survivors' body size and weight management. STUDY DESIGN: In-depth, semi-structured, qualitative interviews. METHODS: Interviews were conducted with 33 providers (eg. oncologists, surgeons, primary care providers, nurses, dietitians) across academic and community clinical settings. They were transcribed, coded, and analyzed thematically using constant comparative analysis. RESULTS: Providers conceptualized weight in relation to acute treatment, cancer outcomes, or overall health/comorbidities. These patterns were reflected in their reported framing of weight discussions, although providers indicated that they counsel patients on weight to varying extents. Perspectives differed based on professional roles and patient populations. Providers reported that survivors are motivated to lose weight, particularly due to comorbidity concerns, but face numerous barriers to doing so. CONCLUSION: Providers described survivor-level and capacity-level factors influencing survivors' weight management. Differences by provider type highlighted the role of provider knowledge, attitudes, and beliefs in clinical encounters. Opportunities for research and intervention include developing and disseminating evidence-based clinical resources for weight management among cancer survivors, addressing capacity barriers, and exploring communication strategies at interpersonal and population levels.

Fatigue in breast cancer survivors: the impact of a mind-body medicine intervention.

PURPOSE/OBJECTIVES: To evaluate a mind-body medicine (MBM) program for its impact on persistent fatigue following breast cancer treatment. DESIGN: Quasiexperimental. SETTING: An urban community hospital and a health department in a semirural county, both in Maryland. SAMPLE: 68 breast cancer survivors who were at least six months postadjuvant chemotherapy and/or radiation therapy and had a baseline fatigue score of 50 or lower per the vitality subscale of the SF-36® Health Survey. METHODS: A 10-week group-based MBM program for breast cancer survivors with persistent fatigue was evaluated using a pretest/post-test study design. MAIN RESEARCH VARIABLES: Sustained change in fatigue severity as measured by the Piper Fatigue Scale (PFS), SF-36 vitality subscale, and 10 cm visual analog scale (VAS). FINDINGS: Participants were 2.6 years post-treatment, with a mean age of 56.8 years. Overall, fatigue scores improved by 40%. The mean PFS improved from a score of 6 (SD = 1.6) at baseline to 4.2 (SD = 2) at the end of the program (p < 0.001), with additional improvement at two months and sustained at six months (X = 3.6, SD = 2, p < 0.001). Results from the SF-36 and VAS also showed significant improvement in fatigue (p < 0.001). CONCLUSIONS: The findings support the use of a holistic MBM intervention to reduce persistent fatigue in breast cancer survivors. Results should be confirmed with a randomized clinical trial. IMPLICATIONS FOR NURSING: Nurses and other healthcare team members can effectively impact persistent fatigue in breast cancer survivors through the use of a multipronged MBM program.

Androgens and musculoskeletal symptoms among breast cancer patients on aromatase inhibitor therapy.

Aromatase inhibitors (AIs), the adjuvant hormonal treatment of choice for postmenopausal estrogen receptor-positive breast cancer, are associated with an increased risk of musculoskeletal symptoms. The underlying cause of the symptoms is often attributed to estrogen depletion, yet all women treated with AIs have low estrogen levels and only a subset develop symptoms. Concentrations of circulating androgens may be mediating factors contributing to these side effects. The purpose of this study was to examine changes in androgen concentrations among women initiating AI therapy and to determine if concentrations are associated with musculoskeletal symptoms. Data were analyzed from a cohort study of 74 breast cancer patients for whom AI therapy was planned. Questionnaire data on symptoms were collected and blood was drawn prior to AI therapy (baseline) and then again at 3 and 6 months after baseline. Blood was assayed for testosterone, androstenedione, dehydroepiandrosterone-sulfate (DHEAS), and sex hormone-binding globulin (SHBG). Free testosterone index (FTI) values were calculated using testosterone and SHBG measurements. The results showed that concentrations of all of the androgens increased over the study period, with statistically significant differences from baseline concentrations observed for the FTI at 3 and 6 months and for DHEAS at 6 months. Additionally, breast cancer patients with new onset or worsening of pain over the study period had a significantly smaller change in mean DHEAS concentration from baseline to 3 months (P = 0.04) and a marginally significant smaller change in mean DHEAS concentration from baseline to 6 months (P = 0.1) compared to those who reported no pain at all time points or no worsening of pain across the study period. Changes in testosterone, androstenedione, and the FTI were not associated with the onset or worsening of pain during the study period. Findings from this study suggest that higher DHEAS concentrations are associated with less AI-associated pain and should be further investigated.

A new model ELISA, based on two monoclonal antibodies, for quantification of fatty acid synthase.

A new model ELISA, based on two monoclonal antibodies, was developed for the quantification of fatty acid synthase (FAS). In this sandwich assay, a monoclonal antibody M6 was used as a capture on Nunc MaxiSorp ELISA/EIA Modules and another monoclonal antibody M3, labeled with biotin, was used as a detection antibody. More than 10 molecules of biotin were labeled on the anti-FAS monoclonal antibody using modified biotinylation conditions. The within- and between-run CVs were less than 10%, and the detection limit was 3.22 ng/mL. Recoveries were 98.54-121.95%, averaging 106.05%. The average FAS concentration obtained from the total 55 healthy volunteers blood was 4.07 +/- 1.81 ng/mL, 4.25 +/- 2.14 ng/mL in women (n = 37) and 3.70 +/- 0.74 ng/mL in men (n = 18). When compared with the previously developed polyclonal-monoclonal ELISA, a different pattern of FAS levels was observed in the supernatant of two cultured breast cancer cell lines in a time course study and there was no linear correlation between the two assays using 215 human blood samples. Thus, this new model FAS-ELISA could be used as an independent assay in measuring clinical samples. In summary, this monoclonal-monoclonal FAS-ELISA is sensitive, accurate, and precise in quantification of fatty acid synthase and has potential as a complementary tool in testing clinical samples.

Prediagnostic toenail cadmium and zinc and subsequent prostate cancer risk.

BACKGROUND: Cadmium is a recognized human lung carcinogen that has also been positively associated with prostate cancer mainly in occupationally exposed men. The association between dietary and supplemental zinc intake and prostate cancer has not been consistent in epidemiologic studies. We evaluated the association between prediagnostic toenail cadmium and zinc concentrations and risk of prostate cancer in a cohort in which the primary route of exposure to cadmium and zinc is the diet. METHODS: Included in the analysis were 115 prostate cancer cases and 227 age-matched controls nested in the prospective CLUE II study located in Washington County, MD. Participants provided toenail samples at baseline in 1989. Furnace atomic absorption and flame atomic absorption were used to determine toenail cadmium and zinc concentrations, respectively. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression models. RESULTS: Median toenail cadmium and zinc concentrations did not statistically significantly differ between prostate cancer cases (cadmium, 45.9 ppb; zinc, 155.3 ppm) and controls (cadmium, 54.5 ppb; zinc, 164.0 ppm). Prostate cancer risk did not increase with increasing concentrations of cadmium (P trend = 0.9) and did not decrease with increasing concentrations of zinc (P trend = 0.2). For both metals, the ORs for the top four fifths were each below 1.0 when compared with the bottom fifth. CONCLUSION: Men who have high toenail cadmium concentrations in the range observed in this general population sample were not at an increased risk for prostate cancer. Although there was no evidence of a linear dose-response, these findings suggest that risk of prostate cancer may be slightly lower among men with moderate and higher zinc intake.

Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer.

Previous prospective studies have raised the possibility that the antioxidantproperties of carotenoids and vitamin E (alpha-tocopherol) and the role of vitamin A (retinol) in cellular differentiation may be associated with a reduced risk of subsequent breast cancer. To investigate the association between serum and plasma concentrations of retinol, retinyl palmitate, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, total-carotenoids, alpha-tocopherol, and gamma-tocopherol with subsequent development of breast cancer, a nested case control study was conducted among female residents of Washington County, Maryland, who had donated blood for a serum bank in 1974 or 1989. Cases (n = 295) and controls (n = 295) were matched on age, race, menopausal status, and date of blood donation, and the analyses were stratified by cohort participation. Median concentrations of beta-carotene, lycopene, and total carotene were significantly lower in cases compared with controls in the 1974 cohort (13.1, 12.5, and 7.9% difference; P = 0.01, 0.04, and 0.04, respectively) and for lutein in the 1989 cohort (6.7% difference; P = 0.02). The risk of developing breast cancer in the highest fifth was approximately half of that of women in the lowest fifth for beta-carotene [odds ratio (OR) = 0.41; 95% confidence interval (CI) 0.22-0.79; P trend = 0.007], lycopene (OR = 0.55; 95% CI 0.29-1.06; P trend = 0.04), and total carotene (OR = 0.55; 95% CI 0.29-1.03; P trend = 0.02) in the 1974 cohort. There was generally a protective association for other micronutrients in both cohorts, although none reached statistical significance. The results suggest that carotenoids may protect against the development of breast cancer.