Grain Legume Consumption Inhibits Colorectal Tumorigenesis: A Meta-Analysis of Human and Animal Studies

Grain legume consumption has been linked in meta-analysis studies to decreased risk of metabolic syndrome, obesity, and cardiovascular diseases; however, the evidence for a chemo-protective effect of grain legume consumption against colorectal tumorigenesis has been considered inconclusive. We conducted a meta-analysis of human and animal studies to evaluate the effect of grain legume consumption on colorectal cancer (CRC) and its precursors. Twelve case-control studies (42,473 controls and 12,408 cases) and 11 prospective cohorts (1,533,527 participants including 12,274 cases) were included in the meta-analysis; the pooled risk ratio (95% confidence interval) for the highest versus the lowest legume intake group based on a random effects model was 0.72 (0.60–0.89) for incident adenoma, 0.91 (0.84–0.99) for prevalent adenoma, and 0.82 (0.74–0.91) for CRC. Fourteen animal studies (355 animals on grain legume diets and 253 animals on control diets) were included in the meta-analysis and showed in all but one study a chemo-preventive effect against colorectal tumorigenesis. Grain legumes contain various compounds (e.g., resistant starch, soluble fiber, insoluble fiber, phytosterols, saponins, phytates, flavonoids, proanthocyanidins, and phenolic acids) that have been shown to inhibit colorectal tumorigenesis in animal studies at concentrations that are relevant for human diets. Grain legume consumption alters several molecular pathways (e.g., p53, mTOR, NF-kB, Akt, and AMPK) that are critical for tumor induction, promotion, and progression. Based on our meta-analysis, daily grain legume consumption confers chemo-preventive effects against CRC

A review and meta-analysis of the association between dairy intake and breast cancer risk in Prospective Cohort Studies

Background: Breast cancer is the most common cancer among women. In 2012, over 220,000 women were diagnosed with breast cancer in the United States. It has been hypothesized that dairy may play a role in breast cancer; however, the evidence has been inconsistent and limited. Proposed mechanisms linking dairy and breast cancer risk include: insulin-like growth factor-1 concentrations; phytanic acid through alpha-methylacyl-CoA racemase (AMACR) expression; and conjugated linoleic acid through eicosanoids production, cell signaling pathways and DNA synthesis. Objective: The aim of this study is to review literature and conduct a meta-analysis on the association between dairy intake and breast cancer risk in prospective cohort studies. Methods: We identified three review/meta-analysis articles on dairy intake and risk of breast cancer (Dong et al. 2011, Moorman et al. 2004 and Zang et al. 2015). A total of 20 studies that were conducted as prospective cohort studies and that reported associations between self-reported dairy intake during adulthood and risk of breast cancer were gathered from these articles. Relative risk (RR) and the corresponding 95% confidence intervals (CI) for comparing the highest and the lowest dairy intake categories were extracted for the meta-analysis. We conducted a meta-analysis of the 19 studies, after excluding one study that did not report 95% CI, using Stata 14.1. Results: For total dairy intake, 10 studies were included and showed a statistically significant inverse association with breast cancer risk [RR (95% CI) = 0.85 (0.75-0.95)]. A total of 12 studies were included for total milk intake and showed a statistically significant inverse association with breast cancer risk [RR (95% CI) = 0.87 (0.75-0.99)]. There were 6 studies included for whole milk intake and there was no statistically significant association with breast cancer risk [RR (95% CI) = 0.95 (0.79-1.11)]. A total of 3 studies were included for low-fat milk intake and did not show an association with breast cancer risk [RR (95% CI) = 0.92 (0.77-1.06)]. Conclusion: Based on our literature review and meta-analysis, total dairy and total milk intakes were statistically significantly inversely associated with breast cancer risk. In contrast, whole milk and low-fat milk intakes were not associated with breast cancer risk. More studies are needed to elucidate potential mechanisms underlying the association between dairy and breast cancer risk

Breast density and polymorphisms in genes coding for CYP1A2 and COMT: the Multiethnic Cohort

BACKGROUND: Mammographic density is a strong predictor of breast cancer risk and is increased by hormone replacement therapy (HRT). Some associations with genetic polymorphisms in enzymes involved in estrogen metabolism have been described. This cross-sectional analysis examined the relation between mammographic density and the CYP1A2*1F and COMT Val(58 )Met polymorphisms among 332 breast cancer cases and 254 controls in the Hawaii component of the Multiethnic Cohort. METHODS: Mammographic density, before diagnosis in cases, was quantified by using a validated computer-assisted method. Blood samples were genotyped by standard PCR/RFLP methods. Adjusted mean percent density was calculated by genotype using mixed models with the unstructured covariance option. RESULTS: A positive association between the C allele in the CYP1A2*1F gene and percent density, but not the dense area, was suggested (p = 0.11). The relation was limited to controls (p = 0.045), postmenopausal women not using HRT (p = 0.08), and normal weight subjects (p = 0.046). We did not observe any relation between the COMT Val(58 )Met polymorphism and breast density. CONCLUSION: The lack of an association between the CYP1A2 genotype and the size of the dense areas suggests an effect on the non-dense, i.e., fatty breast tissue. The discrepancies among studies may be due to differential susceptibility; changes in enzyme activity as a result of the CYP1A2*1F polymorphism may influence breast tissue differently depending on hormonal status. Larger studies with the ability to look at interactions would be useful to elucidate the influence of genetic variation in CYP1A2 and COMT on the risk of developing breast cancer

Prediagnosis Leisure-Time Physical Activity and Lung Cancer Survival: A Pooled Analysis of 11 Cohorts

Background: Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisuretime physical activity (LTPA) with all-cause and lung cancer–specific mortality among incident lung cancer patients. Methods: Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer–specific mortality after adjustment for major prognostic factors and lifetime smoking history. Results: Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate ¼ 20.9%, 95% CI ¼ 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR ¼ 0.93, 95% CI ¼ 0.88 to 0.99), but not with lung cancer–specific mortality (multivariable-adjusted HR ¼ 0.99, 95% CI ¼ 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (Pinteraction ¼ .008 for all-cause mortality and .003 for lung cancer–specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariableadjusted HRs were 0.80 (95% CI¼ 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI¼ 0.65 to 0.99) for lung cancer–specific mortality. Conclusions: Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer

Selenium, Selenoenzymes, Oxidative Stress and Risk of Neoplastic Progression from Barrett's Esophagus: Results from Biomarkers and Genetic Variants

Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA) and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX) 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1) concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85). SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR) = 3.95, 95% confidence intervals (CI) = 1.42–10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31–32.58), but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12–0.69). Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1 concentrations with the risk of EA and aneuploidy, which warrants further investigation

LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance

Recent articles have reported an association between fatty liver disease and systemic insulin resistance in humans, but the causal relationship remains unclear. The liver may contribute to muscle insulin resistance by releasing secretory proteins called hepatokines. Here we demonstrate that leukocyte cell-derived chemotaxin 2 (LECT2), an energy-sensing hepatokine, is a link between obesity and skeletal muscle insulin resistance. Circulating LECT2 positively correlated with the severity of both obesity and insulin resistance in humans. LECT2 expression was negatively regulated by starvation-sensing kinase adenosine monophosphate-activated protein kinase in H4IIEC hepatocytes. Genetic deletion of LECT2 in mice increased insulin sensitivity in the skeletal muscle. Treatment with recombinant LECT2 protein impaired insulin signaling via phosphorylation of Jun NH2-terminal kinase in C2C12 myocytes. These results demonstrate the involvement of LECT2 in glucose metabolism and suggest that LECT2 may be a therapeutic target for obesity-associated insulin resistance. © 2014 by the American Diabetes Association

Mammographic Density, Body Mass Index, and Dietary Habits in Japan and Hawaii

xiii, 96 leavesThe topic of this master's thesis is breast cancer risk and its relationships to one's diet and nutrition. There is evidence that lifestyle, family history, dietary habits, reproductive history, and anthropometric characteristics are associated with the risk of breast cancer. The well-established risk factors for breast cancer are age, reproductive behavior, family history of breast cancer, years of education, and anthropometric and dietary factors. However, when it comes to dietary factors, there needs to be further research to clarify the relationship with the disease. Breast cancer incidence rates differ by ethnicity and also by geographic location. Migrant studies have shown that rates among migrants from a low-risk country to a high-risk country were higher than the rates among women in their homelands. This suggests that the increase in rates among the same ethnic group might be caused by changes in the environment, including dietary habits. The objective of this study was to investigate the association of diet with Body Mass Index (BMI) and breast cancer risk, as measured by mammographic density, among Japanese women in Japan and Japanese and Caucasian women in Hawaiʻi. The validated Food frequency questionnaires (FFQ) were used to assess dietary intake as well as descriptive characteristics, which include demographic, anthropometric and reproductive characteristics. Analysis of Variance was used to compare the differences in descriptive characteristics and diet among the three groups of women. To explore the association between diet and the determinants of BMI and mammographic density, multiple regression was applied. Among the three groups of women in the study, anthropometric and mammographic characteristics differed by ethnicity but not by place of residence. Dietary habits differed considerably by ethnicity and place of residence. It appeared that the diet of Japanese women in Hawaiʻi was a combination of foods eaten in Japan and dietary habits of Caucasian women in Hawaiʻi. Intake of ethanol was associated with BMI in both pre- and postmenopausal women, while association with the other dietary factors differed depending on menopausal status. BMI was more strongly associated with dietary variables among premenopausal women than descriptive characteristics, while it was strongly associated with Japanese ethnicity among postmenopausal women. Intakes of fat, cholesterol, carbohydrates, vitamin A, fish, and eggs were associated with mammographic density in the current study. BMI was the strongest predictor of mammographic density. Dietary intake explained little of the variation in mammographic density. It is still questionable whether mammographic density among different ethnic groups is comparable as an indicator for breast cancer risk. Total dense area of the breast maybe a better indicator. For future studies, it is suggested that associations between body fat distributions, as a possible indicator for breast cancer risk, and diet be examined, adjusted for reproductive histories and biochemical measures for hormones

StifelHeatherM2016-2.pdf

Background: Breast cancer is the most common cancer among women. In 2012, over 220,000 women were diagnosed with breast cancer in the United States. It has been hypothesized that dairy may play a role in breast cancer; however, the evidence has been inconsistent and limited. Proposed mechanisms linking dairy and breast cancer risk include: insulin-like growth factor-1 concentrations; phytanic acid through alpha-methylacyl-CoA racemase (AMACR) expression; and conjugated linoleic acid through eicosanoids production, cell signaling pathways and DNA synthesis. Objective: The aim of this study is to review literature and conduct a meta-analysis on the association between dairy intake and breast cancer risk in prospective cohort studies. Methods: We identified three review/meta-analysis articles on dairy intake and risk of breast cancer (Dong et al. 2011, Moorman et al. 2004 and Zang et al. 2015). A total of 20 studies that were conducted as prospective cohort studies and that reported associations between self-reported dairy intake during adulthood and risk of breast cancer were gathered from these articles. Relative risk (RR) and the corresponding 95% confidence intervals (CI) for comparing the highest and the lowest dairy intake categories were extracted for the meta-analysis. We conducted a meta-analysis of the 19 studies, after excluding one study that did not report 95% CI, using Stata 14.1. Results: For total dairy intake, 10 studies were included and showed a statistically significant inverse association with breast cancer risk [RR (95% CI) = 0.85 (0.75-0.95)]. A total of 12 studies were included for total milk intake and showed a statistically significant inverse association with breast cancer risk [RR (95% CI) = 0.87 (0.75-0.99)]. There were 6 studies included for whole milk intake and there was no statistically significant association with breast cancer risk [RR (95% CI) = 0.95 (0.79-1.11)]. A total of 3 studies were included for low-fat milk intake and did not show an association with breast cancer risk [RR (95% CI) = 0.92 (0.77-1.06)]. Conclusion: Based on our literature review and meta-analysis, total dairy and total milk intakes were statistically significantly inversely associated with breast cancer risk. In contrast, whole milk and low-fat milk intakes were not associated with breast cancer risk. More studies are needed to elucidate potential mechanisms underlying the association between dairy and breast cancer risk

StifelHeatherM2016.pdf

Background: Breast cancer is the most common cancer among women. In 2012, over 220,000 women were diagnosed with breast cancer in the United States. It has been hypothesized that dairy may play a role in breast cancer; however, the evidence has been inconsistent and limited. Proposed mechanisms linking dairy and breast cancer risk include: insulin-like growth factor-1 concentrations; phytanic acid through alpha-methylacyl-CoA racemase (AMACR) expression; and conjugated linoleic acid through eicosanoids production, cell signaling pathways and DNA synthesis. Objective: The aim of this study is to review literature and conduct a meta-analysis on the association between dairy intake and breast cancer risk in prospective cohort studies. Methods: We identified three review/meta-analysis articles on dairy intake and risk of breast cancer (Dong et al. 2011, Moorman et al. 2004 and Zang et al. 2015). A total of 20 studies that were conducted as prospective cohort studies and that reported associations between self-reported dairy intake during adulthood and risk of breast cancer were gathered from these articles. Relative risk (RR) and the corresponding 95% confidence intervals (CI) for comparing the highest and the lowest dairy intake categories were extracted for the meta-analysis. We conducted a meta-analysis of the 19 studies, after excluding one study that did not report 95% CI, using Stata 14.1. Results: For total dairy intake, 10 studies were included and showed a statistically significant inverse association with breast cancer risk [RR (95% CI) = 0.85 (0.75-0.95)]. A total of 12 studies were included for total milk intake and showed a statistically significant inverse association with breast cancer risk [RR (95% CI) = 0.87 (0.75-0.99)]. There were 6 studies included for whole milk intake and there was no statistically significant association with breast cancer risk [RR (95% CI) = 0.95 (0.79-1.11)]. A total of 3 studies were included for low-fat milk intake and did not show an association with breast cancer risk [RR (95% CI) = 0.92 (0.77-1.06)]. Conclusion: Based on our literature review and meta-analysis, total dairy and total milk intakes were statistically significantly inversely associated with breast cancer risk. In contrast, whole milk and low-fat milk intakes were not associated with breast cancer risk. More studies are needed to elucidate potential mechanisms underlying the association between dairy and breast cancer risk

Vegetarian diets and risk of all-cause mortality in a population-based prospective study in the United States

Abstract The popularity of vegetarian diets has increased the need for studies on long-term health outcomes. A limited number of studies, including only one study from a non-vegetarian population, investigated the risk of mortality with self-identified vegetarianism and reported inconsistent results. This study evaluated prospective associations between vegetarian diets and all-cause mortality among 117,673 participants from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial cohort study. Vegetarian diet status was self-identified on the questionnaire. Deaths were ascertained from follow-up questionnaires and the National Death Index database. Multivariable Cox regression models were used to estimate the risk of all-cause mortality in hazard ratio (HR) and 95% confidence intervals (CI). By diet group, there were 116,894 omnivores (whose diet does not exclude animal products), 329 lacto- and/or ovo-vegetarians (whose diet excludes meat, but includes dairy and/or eggs), 310 pesco-vegetarians (whose diet excludes meat except for fish and seafood) and 140 vegans (whose diet excludes all animal products). After an average follow-up of 18 years, 39,763 participants were deceased. The risk of all-cause mortality did not statistically significantly differ among the four diet groups. Comparing with the omnivore group, the HR (95% CI) were 0.81 (0.64–1.03) for pesco-vegetarian group, 0.99 (0.80–1.22) for lacto- and/or ovo-vegetarian group and 1.27 (0.99–1.63) for vegan group, respectively. Similarly, mortality risk did not differ when comparing lacto- and/or ovo-vegetarians plus vegans with meat/fish eaters (omnivores and pesco-vegetarians) (HR [95% CI] = 1.09 [0.93–1.28]). As this study is one of the two studies of vegetarianism and mortality in non-vegetarian populations, further investigation is warranted