Circulating Isovalerylcarnitine and Lung Cancer Risk: Evidence from Mendelian Randomization and Prediagnostic Blood Measurements.

BACKGROUND: Tobacco exposure causes 8 of 10 lung cancers, and identifying additional risk factors is challenging due to confounding introduced by smoking in traditional observational studies. MATERIALS AND METHODS: We used Mendelian randomization (MR) to screen 207 metabolites for their role in lung cancer predisposition using independent genome-wide association studies (GWAS) of blood metabolite levels (n = 7,824) and lung cancer risk (n = 29,266 cases/56,450 controls). A nested case-control study (656 cases and 1,296 matched controls) was subsequently performed using prediagnostic blood samples to validate MR association with lung cancer incidence data from population-based cohorts (EPIC and NSHDS). RESULTS: An MR-based scan of 207 circulating metabolites for lung cancer risk identified that blood isovalerylcarnitine (IVC) was associated with a decreased odds of lung cancer after accounting for multiple testing (log10-OR = 0.43; 95% CI, 0.29-0.63). Molar measurement of IVC in prediagnostic blood found similar results (log10-OR = 0.39; 95% CI, 0.21-0.72). Results were consistent across lung cancer subtypes. CONCLUSIONS: Independent lines of evidence support an inverse association of elevated circulating IVC with lung cancer risk through a novel methodologic approach that integrates genetic and traditional epidemiology to efficiently identify novel cancer biomarkers. IMPACT: Our results find compelling evidence in favor of a protective role for a circulating metabolite, IVC, in lung cancer etiology. From the treatment of a Mendelian disease, isovaleric acidemia, we know that circulating IVC is modifiable through a restricted protein diet or glycine and L-carnatine supplementation. IVC may represent a modifiable and inversely associated biomarker for lung cancer.

A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

BACKGROUND: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. OBJECTIVES: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. MEDTHODS: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. RESULTS: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. CONCLUSIONS: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.

Assessing the causal association between 25-hydroxyvitamin D and the risk of oral and oropharyngeal cancer using Mendelian randomization.

Circulating 25-hydroxyvitamin D (25OHD) is an appealing potential intervention for cancer risk and has been associated with oral and oropharyngeal cancer risk but evidence is inconsistent. The availability of genetic variants, uncorrelated with known confounders, but predictive of 25OHD and genetic data in a large oral and oropharyngeal cancer collaboration aids causal inference when assessing this association. A total of 5,133 oral and oropharyngeal cancer cases and 5,984 controls with genetic data were included in the study. Participants were based in Europe, North America and South America and were part of the Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Five genetic variants reliably associated with circulating 25OHD were used to create a relative genetic measure of 25OHD. In the absence of measured 25OHD, two-sample Mendelian randomization using individual level outcome data were used to estimate causal odds ratios (OR) for cancer case status per standard deviation increase in log25OHD. Analyses were replicated in an independent population-based cohort (UK Biobank). In the GAME-ON study, there was little evidence of a causal association between circulating 25OHD and oral cancer (OR = 0.86 [0.68;1.09], p = 0.22), oropharyngeal cancer (OR = 1.28 [0.72;2.26], p = 0.40) or when sites were combined (OR = 1.01 [0.74;1.40], p = 0.93). Replication in UK Biobank and pooled estimates produced similar results. Our study suggests that a clinically relevant protective effect of 25OHD on oral and oropharyngeal cancer risk is unlikely and supplementation of the general population with 25OHD is unlikely to be beneficial in preventing these cancers.

Prediagnostic Calcium Intake and Lung Cancer Survival: A Pooled Analysis of 12 Cohort Studies.

Background: Lung cancer is the leading cause of cancer death. Little is known about whether prediagnostic nutritional factors may affect survival. We examined the associations of prediagnostic calcium intake from foods and/or supplements with lung cancer survival.Methods: The present analysis included 23,882 incident, primary lung cancer patients from 12 prospective cohort studies. Dietary calcium intake was assessed using food-frequency questionnaires at baseline in each cohort and standardized to caloric intake of 2,000 kcal/d for women and 2,500 kcal/d for men. Stratified, multivariable-adjusted Cox regression was applied to compute hazard ratios (HR) and 95% confidence intervals (CI).Results: The 5-year survival rates were 56%, 21%, and 5.7% for localized, regional, and distant stage lung cancer, respectively. Low prediagnostic dietary calcium intake (<500-600 mg/d, less than half of the recommendation) was associated with a small increase in risk of death compared with recommended calcium intakes (800-1,200 mg/d); HR (95% CI) was 1.07 (1.01-1.13) after adjusting for age, stage, histology, grade, smoking status, pack-years, and other potential prognostic factors. The association between low calcium intake and higher lung cancer mortality was evident primarily among localized/regional stage patients, with HR (95% CI) of 1.15 (1.04-1.27). No association was found for supplemental calcium with survival in the multivariable-adjusted model.Conclusions: This large pooled analysis is the first, to our knowledge, to indicate that low prediagnostic dietary calcium intake may be associated with poorer survival among early-stage lung cancer patients.Impact: This multinational prospective study linked low calcium intake to lung cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(7); 1060-70. ©2017 AACR.

Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls.

BACKGROUND: Folate and vitamin B12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear. OBJECTIVE: To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade. DESIGN, SETTING, AND PARTICIPANTS: A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incident PCa and subtype by stage and grade. RESULTS AND LIMITATIONS: Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], ptrend=0.018, for folate and 1.12 [95% CI, 1.01-1.25], ptrend=0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity<0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; ptrend=0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12 with risk by stage or grade of disease (pheterogeneity>0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation. CONCLUSIONS: The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation. PATIENT SUMMARY: Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.

Fish consumption and mortality in the European Prospective Investigation into Cancer and Nutrition cohort.

Fish is a source of important nutrients and may play a role in preventing heart diseases and other health outcomes. However, studies of overall mortality and cause-specific mortality related to fish consumption are inconclusive. We examined the rate of overall mortality, as well as mortality from ischaemic heart disease and cancer in relation to the intake of total fish, lean fish, and fatty fish in a large prospective cohort including ten European countries. More than 500,000 men and women completed a dietary questionnaire in 1992-1999 and were followed up for mortality until the end of 2010. 32,587 persons were reported dead since enrolment. Hazard ratios and their 99% confidence interval were estimated using Cox proportional hazard regression models. Fish consumption was examined using quintiles based on reported consumption, using moderate fish consumption (third quintile) as reference, and as continuous variables, using increments of 10 g/day. All analyses were adjusted for possible confounders. No association was seen for fish consumption and overall or cause-specific mortality for both the categorical and the continuous analyses, but there seemed to be a U-shaped trend (p < 0.000) with fatty fish consumption and total mortality and with total fish consumption and cancer mortality (p = 0.046).

Affective responses to qigong: a pilot study of regular practitioners.

Single sessions of Qigong have been associated with increased positive affect/emotional benefits. In the present study the aim was to refine the present understanding by using newly developed research methodologies. Therefore, affective reactions were studied in a group performing Qigong through pre-, during, and post-assessments using a modified version of the short Swedish Core Affect Scale complemented with open-ended questions. Affect was measured on a group and individual level. The results showed a shift during Qigong toward increased pleasant activated and deactivated affect in the group of 46 women who regularly practice Qigong. Inter-individual responses displayed positive affective responses, which also increased as the bout proceeded for the majority of practitioners. Acknowledging some limitations, these findings have practical implications for the enhancement of positive affect and subjective well-being.

Qigong and mindfulness-based mood recovery: exercise experiences from a single case.

Sara, the participant in this single case study, had to leave work due to burnout. She is now recovered and working, but still complains of disturbed moods and worries about getting burned out again. The aim of this study was to, by way of Qigong and mindfulness exercise, increase the participant's positive mood to a functional level and to increase exercise experiences by combining mindfulness and Qigong practice. The professional practice intervention was planned to last twelve weeks, combining mindfulness practice and three different Qigong exercise techniques. Exercise behavior was noted daily, stress-energy and wellness were followed up weekly, and mindfulness was followed up after four, nine and 12 weeks. Sara feels that her moods (more energy, wellness and joy, as well as less stress and worry) have stabilized at a high level (good to very good), and her mindfulness score also improved to a high level (4.2 on a six-point scale). Sara also states that she enjoys life more: accepts stressful situations as they are, is less worried about becoming burned out again, and is more open to life. Exercise professionals may use mindfulness practice and Qigong exercise when recovering moods, probably even better in preventing burnout syndromes.

Fatty acid patterns and risk of prostate cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Fatty acids in blood may be related to the risk of prostate cancer, but epidemiologic evidence is inconsistent. Blood fatty acids are correlated through shared food sources and common endogenous desaturation and elongation pathways. Studies of individual fatty acids cannot take this into account, but pattern analysis can. Treelet transform (TT) is a novel method that uses data correlation structures to derive sparse factors that explain variation. OBJECTIVE: The objective was to gain further insight in the association between plasma fatty acids and risk of prostate cancer by applying TT to take data correlations into account. DESIGN: We reanalyzed previously published data from a case-control study of prostate cancer nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. TT was used to derive factors explaining the variation in 26 plasma phospholipid fatty acids of 962 incident prostate cancer cases matched to 1061 controls. Multiple imputation was used to deal with missing data in covariates. ORs of prostate cancer according to factor scores were determined by using multivariable conditional logistic regression. RESULTS: Four simple factors explained 38% of the variation in plasma fatty acids. A high score on a factor reflecting a long-chain n-3 PUFA pattern was associated with greater risk of prostate cancer (OR for highest compared with lowest quintile: 1.36; 95% CI: 0.99, 1.86; P-trend = 0.041). CONCLUSION: Pattern analyses using TT groupings of correlated fatty acids indicate that intake or metabolism of long-chain n-3 PUFAs may be relevant to prostate cancer etiology.

Acute psychological responses to Qigong exercise of varying durations.

Qigong exercise has been shown to induce acute psychological changes of a positive nature; but whether longer durations have greater effects than shorter ones is not known. Forty-one regular qigong practitioners therefore engaged in either 30 or 60 min of qigong exercise within a randomized cross-over design. Measures of mood, anxiety, activation, and hedonic tone were obtained pre- and post-exercise. Results showed benefits of the same magnitude in the two conditions: more positive mood states, reduced state anxiety, and enhanced perceived pleasure. Thirty minutes of qigong exercise thereby seems to be sufficient to provide psychological benefits, and with no additional benefits detected after 60 min. This finding is important for those having little time or motivation to engage in activities of longer durations. In addition, health professionals prescribing exercise for health benefits can prescribe shorter exercise sessions with confidence knowing that positive psychological effects can also occur after a shorter exercise bout.

Qigong exercise with concentration predicts increased health.

Regular physical activity has many positive health effects. Despite this, approximately 50% of all adults are not exercising enough to enjoy better health and may, therefore, need an alternative to vigorous physical exercise. Qigong offers a gentle way to exercise the body. A questionnaire sample of 253 participants was collected and correlations with the variable health-now were analyzed. Results showed that health-now was positively correlated with number of completed qigong courses (p < 0.05), with level of concentration (p < 0.01), session-time (p < 0.01), and years of practice (p < 0.05). Among these variables, concentration predicts an increased feeling of health (R(2) = 0.092). Qigong exercise thereby seems to offer a viable alternative to other more vigorous physical activities when wellness is the primary goal. When interpreted using self-determination theory, qigong seems to satisfy needs related to autonomy, competence and relatedness, thereby, primarily attracting individuals who are intrinsically motivated.