Colorectal cancer and diet in Scotland

Introduction Colorectal cancer is a cancer that forms in the tissues of the colon and/ or rectum and more than 95% of colorectal cancers are adenocarcinomas. It is the third most common cancer in incidence and mortality rates, accounting for 9% of all cancer cases and for 8% of all cancer related deaths (2002). The established risk factors of colorectal cancer include personal or family history of previous colorectal cancer or adenomatous polyps, chronic bowel inflammatory disease and presence of any of the hereditary syndromes. In addition, due to the fact that the majority of colorectal cancer cases (approximately 90%) occur after the age of 50, advanced age is also considered as a risk factor. Finally, evidence for significant associations between colorectal cancer and other risk factors, including diet, body weight, physical activity, smoking, alcohol intake, NSAIDs intake and HRT in post-menopausal women, is promising and increasing. Aims and objectives The main aims of this project were: 1) to investigate the associations between colorectal cancer and specific nutrients, including flavonoids, fatty acids, folate, vitamin B2, vitamin B6, vitamin B12, alcohol, vitamin D and calcium (prior hypotheses 1-4) and 2) to conduct an overall as well as forward and backward stepwise regression analyses of demographic, lifestyle and dietary risk factors. Methods The analysis of this thesis was based on a population-based case-control study of colorectal cancer (Scottish Colorectal Cancer Study; SOCCS). In total 3,417 colorectal cancer cases and 3,396 controls were recruited in the study. Dietary and lifestyle data were collected by two questionnaires (Lifestyle & Cancer and Food Frequency Questionnaire) and were available for 2,061 cases and 2,776 controls. For the analysis of the first two hypotheses (flavonoids and fatty acids) a matched dataset of 1,489 casecontrol pairs was used and conditional logistic regression models were applied, whereas for the analysis of the last two hypotheses (folate, vitamin B2, vitamin B6, vitamin B12, alcohol, vitamin D and calcium) an unmatched dataset including 2,061 cases and 2,776 v controls was used and unconditional logistic regression models were applied. For the overall and stepwise regression analyses the unmatched dataset was used (2,061 cases and 2,776 controls). Forward and backward stepwise regression was applied on three different sets of variables and the stability of the resultant models was checked in 100 bootstrap samples. Results Regarding the first two hypotheses, statistically significant odds ratios (ORs) (matched on sex, age and health board are and adjusted for family history of cancer, BMI, physical activity, smoking, and intakes of total energy, fibre, alcohol and NSAIDs) for highest versus lowest intakes (quartiles) were observed for flavonols OR (95% CI), p-value for trend: 0.78 (0.60, 0.99), 0.08) and for the individual flavonoid compounds quercetin and catechin (OR (95% CI), p-value for trend: 0.77 (0.60, 0.99), 0.04; 0.75 (0.58-0.97), 0.02; respectively); for the 3PUFAs fatty acids (OR (95% CI), p-value for trend: 0.75 (0.59, 0.97), 0.01) and for the individual fatty acids stearic acid, EPA and DHA (OR (95% CI), p-value for trend: 1.46 (1.11, 1.91), 0.01; 0.74 (0.58, 0.95), 0.02; 0.74 (0.58, 0.95), 0.02; respectively). Regarding the last two hypotheses, statistically significant odds ratios (ORs) (adjusted for age, sex, deprivation score, family history of cancer, BMI, physical activity, smoking, and intakes of total energy, fibre, alcohol and NSAIDs) for highest versus lowest intakes (quartiles) were observed for vitamin B6, vitamin B12 and alcohol (OR (95% CI), p-value for trend: 0.86 (0.72, 1.03), 0.08; 0.80 (0.67, 0.97), 0.05; 0.83 (0.68, 1.00), 0.03); and for vitamin D (OR (95% CI), p-value for trend: 0.83 (0.69, 0.99), 0.03). Regarding the second aim of the project, several risk factors were found to be significantly associated with colorectal cancer in the overall analysis including demographic and lifestyle factors (family history of cancer, NSAIDs intake, dietary energy intake, HRT intake and physical activity), food group variables (vegetables, eggs, sweets, fruit/ vegetable juice, oily fish, coffee, fruit, savoury foods and white fish) and nutrient variables (tMUFAs, 3PUFAs, SFAs, tFAs, MUFAs, quercetin, catechin, phytoestrogen, cholesterol, fibre, protein, starch, magnesium, potassium, manganese, copper, iron, zinc, phosphorus, selenium, niacin, vitamin B6, carotenes, vitamin C, vi vitamin A, potential niacin, biotin, folate, pantothenic acid, vitamin D, vitamin B1 and vitamin B12). In addition, the variables that were selected to be included in 100% of the models after applying forward and backward stepwise regression analyses were family history, NSAIDs, sweets and fruit/ vegetable juice. Finally according to the findings from the bootstrap analysis, the variables that were selected to be included in models for the majority of the bootstrap samples (more than 90%) were family history, NSAIDs, dietary energy, eggs, sweets, fruit/ vegetable juice and white fish. Discussion The particular dietary factors that were found to be inversely associated with colorectal cancer after applying several multivariable logistic regression models were: flavonols, quercetin, catechin, 3PUFAs, EPA, DHA, vitamin B6, vitamin B12 and vitamin D. In addition, high intakes of stearic acid were found to be positively associated with colorectal cancer. In contrast, high intakes of dietary and total folate were associated with a decreased colorectal cancer risk in the energy-adjusted model, but this inverse association was attenuated after further adjustment for several confounding factors including fibre. Regarding alcohol intake, when it was divided into quartiles, high alcohol consumption was associated with a statistically significant and dose-dependent decreased colorectal cancer risk. However, when alcohol intake was divided in categories an increased colorectal cancer risk for intakes of higher than 60 g/day was observed. Intakes of 3PUFAs, vitamin D and vitamin B12 were highly correlated due to having the same food source (oily fish) and therefore it is difficult to draw specific conclusions regarding which nutrient is truly associated with colorectal cancer and which not. Finally, it was observed that for calcium intakes to be inversely associated with colorectal cancer, a dosage of 1500mg/day or higher was necessary. The majority of these results are in accordance with results of previous epidemiological and laboratory studies; however their confirmation in further large-scale studies is required. Results from the overall and stepwise regression analysis supported previous findings of an increased colorectal cancer risk due to a high or moderate family history risk. In addition, high intakes of dietary energy were found to be positively associated with increased colorectal cancer risk in the overall analysis and in addition dietary energy was vii selected to be included in the majority of the stepwise regression models. On the other hand, regular intake of NSAIDs was found to be inversely associated with colorectal cancer risk in the overall analysis and in the majority of the stepwise regression models. Finally, the overall and stepwise regression analyses generated a few new hypotheses suggesting that low intakes of fruit/ vegetable juice, eggs, white fish and sweets (a combined variable of high-fat and high-sugar foods) and high intakes of coffee and magnesium were associated with a decreased colorectal cancer. These findings, though interesting and important for generation of new hypotheses, need further investigation (as prior hypotheses) in large-scale observational studies

Estimating the incidence of colorectal cancer in Sub-Saharan Africa:A systematic analysis

Background Nearly two–thirds of annual mortality worldwide is attributable to non–communicable diseases (NCDs), with 70% estimated to occur in low– and middle–income countries (LMIC). Colorectal cancer (CRC) accounts for over 600 000 deaths annually, but data concerning cancer rates in LMIC is very poor. This study analyses the data available to produce an estimate of the incidence of colorectal cancer in Sub–Saharan Africa (SSA). Methods Data for this analysis came from two main sources: a systematic search of Medline, EMBASE and Global Health which found 15 published data sets, and an additional 42 unpublished data sets which were sourced from the IARC and individual cancer registries. Data for case rates by age and sex, as well as population denominators were extracted and analysed to produce an estimate of incidence. Results: The crude incidence of CRC in SSA for both sexes was found to be 4.04 per 100 000 population (4.38 for men and 3.69 for women). Incidence increased with age with the highest rates in Southern Africa, particularly in South Africa. The rates of CRC in SSA were much lower than those reported for high–income countries. Conclusion Few health services in SSA are equipped to provide timely diagnosis and treatment of cancer in SSA. In addition, data collection systems are weak, meaning that the available statistics may underestimate the burden of disease. In order to improve health care services it is vital that accurate measurements of disease burden are available to policy maker

Aetiology of community-acquired neonatal sepsis in low and middle income countries

99% of the approximate 1 million annual neonatal deaths from life-threatening invasive bacterial infections occur in developing countries, at least 50% of which are from home births or community settings. Data concerning aetiology of sepsis in these settings are necessary to inform targeted therapy and devise management guidelines. This review describes and analyses the bacterial aetiology of community-acquired neonatal sepsis in developing countries

Vitamin D and multiple health outcomes:umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials

Objective To evaluate the breadth, validity, and presence of biases of the associations of vitamin D with diverse outcomes. Design Umbrella review of the evidence across systematic reviews and meta-analyses of observational studies of plasma 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D concentrations and randomised controlled trials of vitamin D supplementation. Data sources Medline, Embase, and screening of citations and references. Eligibility criteria Three types of studies were eligible for the umbrella review: systematic reviews and meta-analyses that examined observational associations between circulating vitamin D concentrations and any clinical outcome; and meta-analyses of randomised controlled trials assessing supplementation with vitamin D or active compounds (both established and newer compounds of vitamin D). Results 107 systematic literature reviews and 74 meta-analyses of observational studies of plasma vitamin D concentrations and 87 meta-analyses of randomised controlled trials of vitamin D supplementation were identified. The relation between vitamin D and 137 outcomes has been explored, covering a wide range of skeletal, malignant, cardiovascular, autoimmune, infectious, metabolic, and other diseases. Ten outcomes were examined by both meta-analyses of observational studies and meta-analyses of randomised controlled trials, but the direction of the effect and level of statistical significance was concordant only for birth weight (maternal vitamin D status or supplementation). On the basis of the available evidence, an association between vitamin D concentrations and birth weight, dental caries in children, maternal vitamin D concentrations at term, and parathyroid hormone concentrations in patients with chronic kidney disease requiring dialysis is probable, but further studies and better designed trials are needed to draw firmer conclusions. In contrast to previous reports, evidence does not support the argument that vitamin D only supplementation increases bone mineral density or reduces the risk of fractures or falls in older people. Conclusions Despite a few hundred systematic reviews and meta-analyses, highly convincing evidence of a clear role of vitamin D does not exist for any outcome, but associations with a selection of outcomes are probable