Ruth H. Keogh

Dietary Fiber and Colorectal Cancer Risk: A Nested Case–Control Study Using Food Diaries

BACKGROUND Results of epidemiological studies of dietary fiber and colorectal cancer risk have not been consistent, possibly because of attenuation of associations due to measurement error in dietary exposure ascertainment. METHODS To examine the association between dietary fiber intake and colorectal cancer risk, we conducted a prospective case-control study nested within seven UK cohort studies, which included 579 case patients who developed incident colorectal cancer and 1996 matched control subjects. We used standardized dietary data obtained from 4- to 7-day food diaries that were completed by all participants to calculate the odds ratios for colorectal, colon, and rectal cancers with the use of conditional logistic regression models that adjusted for relevant covariates. We also calculated odds ratios for colorectal cancer by using dietary data obtained from food-frequency questionnaires that were completed by most participants. All statistical tests were two-sided. RESULTS Intakes of absolute fiber and of fiber intake density, ascertained by food diaries, were statistically significantly inversely associated with the risks of colorectal and colon cancers in both age-adjusted models and multivariable models that adjusted for age; anthropomorphic and socioeconomic factors; and dietary intakes of folate, alcohol, and energy. For example, the multivariable-adjusted odds ratio of colorectal cancer for highest vs the lowest quintile of fiber intake density was 0.66 (95% confidence interval = 0.45 to 0.96). However, no statistically significant association was observed when the same analysis was conducted using dietary data obtained by food-frequency questionnaire (multivariable odds ratio = 0.88, 95% confidence interval = 0.57 to 1.36). CONCLUSIONS Intake of dietary fiber is inversely associated with colorectal cancer risk. Methodological differences (ie, study design, dietary assessment instruments, definition of fiber) may account for the lack of convincing evidence for the inverse association between fiber intake and colorectal cancer risk in some previous studies.

The Association between Time Spent Outdoors and Myopia in Children and Adolescents: A Systematic Review and Meta-analysis.

OBJECTIVE To summarize relevant evidence investigating the association between time spent outdoors and myopia in children and adolescents (up to 20 years). DESIGN Systematic review and meta-analysis. PARTICIPANTS Results from 7 cross-sectional studies were pooled in a meta-analysis. A further 16 studies (8 cross-sectional not meeting criteria for meta-analysis; 7 prospective cohort studies; 1 randomized, controlled trial [RCT]) were reported in the systematic review. METHODS The literature search included 4 databases (Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials [CENTRAL]), and reference lists of retrieved studies. Estimates of association were pooled using random effects meta-analysis. We summarized data examining the association between time spent outdoors and prevalent myopia, incident myopia, and myopic progression. MAIN OUTCOME MEASURES Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for myopia for each additional hour spent outdoors per week from a meta-analysis. RESULTS The pooled OR for myopia indicated a 2% reduced odds of myopia per additional hour of time spent outdoors per week, after adjustment for covariates (OR, 0.981; 95% CI, 0.973-0.990; P<0.001; I(2), 44.3%). This is equivalent to an OR of 0.87 for an additional hour of time spent outdoors each day. Three prospective cohort studies provided estimates of risk of incident myopia according to time spent outdoors, adjusted for possible confounders, although estimates could not be pooled, and the quality of studies and length of follow-up times varied. Three studies (2 prospective cohort and 1 RCT) investigated time spent outdoors and myopic progression and found increasing time spent outdoors significantly reduced myopic progression. CONCLUSIONS The overall findings indicate that increasing time spent outdoors may be a simple strategy by which to reduce the risk of developing myopia and its progression in children and adolescents. Therefore, further RCTs are warranted to investigate the efficacy of increasing time outdoors as a possible intervention to prevent myopia and its progression.

Sputum biomarkers and the prediction of clinical outcomes in patients with cystic fibrosis

Lung function, acute pulmonary exacerbations (APE), and weight are the best clinical predictors of survival in cystic fibrosis (CF); however, underlying mechanisms are incompletely understood. Biomarkers of current disease state predictive of future outcomes might identify mechanisms and provide treatment targets, trial endpoints and objective clinical monitoring tools. Such CF-specific biomarkers have previously been elusive. Using observational and validation cohorts comprising 97 non-transplanted consecutively-recruited adult CF patients at the Intermountain Adult CF Center, University of Utah, we identified biomarkers informative of current disease and predictive of future clinical outcomes. Patients represented the majority of sputum producers. They were recruited March 2004-April 2007 and followed through May 2011. Sputum biomarker concentrations were measured and clinical outcomes meticulously recorded for a median 5.9 (interquartile range 5.0 to 6.6) years to study associations between biomarkers and future APE and time-to-lung transplantation or death. After multivariate modeling, only high mobility group box-1 protein (HMGB-1, mean = 5.84 [log ng/ml], standard deviation [SD] = 1.75) predicted time-to-first APE (hazard ratio [HR] per log-unit HMGB-1 = 1.56, p-value = 0.005), number of future APE within 5 years (0.338 APE per log-unit HMGB-1, p<0.001 by quasi-Poisson regression) and time-to-lung transplantation or death (HR = 1.59, p = 0.02). At APE onset, sputum granulocyte macrophage colony stimulating factor (GM-CSF, mean 4.8 [log pg/ml], SD = 1.26) was significantly associated with APE-associated declines in lung function (−10.8 FEV1% points per log-unit GM-CSF, p<0.001 by linear regression). Evaluation of validation cohorts produced similar results that passed tests of mutual consistency. In CF sputum, high HMGB-1 predicts incidence and recurrence of APE and survival, plausibly because it mediates long-term airway inflammation. High APE-associated GM-CSF identifies patients with large acute declines in FEV1%, possibly providing a laboratory-based objective decision-support tool for determination of an APE diagnosis. These biomarkers are potential CF reporting tools and treatment targets for slowing long-term progression and reducing short-term severity.

Effects of body size and sociodemographic characteristics on differences between self-reported and measured anthropometric data in middle-aged men and women: the EPIC-Norfolk study

Background/Objectives:To investigate the effects of body size and sociodemographic characteristics on differences between self-reported (SR) and measured anthropometric data in men and women.Subjects/Methods:This study comprises 9933 men and 11 856 women aged 39–79 years at baseline survey (1993–1997) in the EPIC-Norfolk study (Norfolk arm of the European Investigation into Cancer and Nutrition Study). The effects of sex, measured height, weight, age group, educational level and social class on differences between SR and measured weight, height, body mass index (BMI), waist, hip and waist-to-hip ratio (WHR) were examined.Results:There were systematic differences between SR and measured anthropometric measurements by sex, measured height, weight and sociodemographic characteristics. Height was overestimated in both sexes while weight, waist, hip, and consequently, BMI and WHR were underestimated. Being male, shorter, heavier, older, and having no educational qualifications and manual occupation were independently associated with overreporting of height, and underreporting of weight was associated independently with being female, shorter, heavier, younger age, and higher education level and social class. Underreporting of waist circumference was strongly associated with being female and higher measured waist circumference, while underreporting of hip circumference was associated with being male and higher measured hip circumference. Furthermore, there was substantial degree of misclassification of BMI and waist circumference categories for both general and central obesity associated with SR data.Conclusions:These findings suggest that errors in SR anthropometric data, especially waist and hip circumference are influenced by actual body size as well as sociodemographic characteristics. These systematic differences may influence associations between SR anthropometric measures and health outcomes in epidemiological studies.

A toolkit for measurement error correction, with a focus on nutritional epidemiology

Exposure measurement error is a problem in many epidemiological studies, including those using biomarkers and measures of dietary intake. Measurement error typically results in biased estimates of exposure-disease associations, the severity and nature of the bias depending on the form of the error. To correct for the effects of measurement error, information additional to the main study data is required. Ideally, this is a validation sample in which the true exposure is observed. However, in many situations, it is not feasible to observe the true exposure, but there may be available one or more repeated exposure measurements, for example, blood pressure or dietary intake recorded at two time points. The aim of this paper is to provide a toolkit for measurement error correction using repeated measurements. We bring together methods covering classical measurement error and several departures from classical error: systematic, heteroscedastic and differential error. The correction methods considered are regression calibration, which is already widely used in the classical error setting, and moment reconstruction and multiple imputation, which are newer approaches with the ability to handle differential error. We emphasize practical application of the methods in nutritional epidemiology and other fields. We primarily consider continuous exposures in the exposure-outcome model, but we also outline methods for use when continuous exposures are categorized. The methods are illustrated using the data from a study of the association between fibre intake and colorectal cancer, where fibre intake is measured using a diet diary and repeated measures are available for a subset.

Dietary fat and breast cancer: comparison of results from food diaries and food-frequency questionnaires in the UK Dietary Cohort Consortium

BACKGROUND Epidemiologic studies of dietary fat and breast cancer risk are inconsistent, and it has been suggested that a true relation may have been obscured by the imprecise measurement of fat intake. OBJECTIVE We examined associations of fat with breast cancer risk by using estimates of fat intake from food diaries and food-frequency questionnaires (FFQs) pooled from 4 prospective studies in the United Kingdom. DESIGN A total of 657 cases of breast cancer in premenopausal and postmenopausal women were matched on study, age, and recruitment date with 1911 control subjects. Nutrient intakes were estimated from food diaries and FFQs. Conditional logistic regression was used to estimate ORs for breast cancer associated with total, saturated, monounsaturated, and polyunsaturated fat intakes with adjustment for relevant covariates. RESULTS Neither the food diaries nor the FFQs showed any positive associations between fat intake and overall breast cancer risk. ORs (95% CIs) for the highest compared with lowest quintiles of percentage of energy from total fat were 0.90 (0.66, 1.23) for food diaries and 0.80 (0.59, 1.09) for FFQs. CONCLUSION In this study, breast cancer risk was not associated with fat intake in middle-aged women in the United Kingdom, irrespective of whether diet was measured by food diaries or by FFQs.

Racial/ethnic and socioeconomic disparities in survival among children with acute lymphoblastic leukemia in California, 1988-2011: A population-based observational study

Despite advances in treatment, survival from acute lymphoblastic leukemia (ALL) remains lower among non‐White children than White children in the US. We investigated the association of race/ethnicity and socioeconomic status (SES) with survival.

Intake of dietary fats and colorectal cancer risk: Prospective findings from the UK Dietary Cohort Consortium

INTRODUCTION Epidemiologic evidence for an association between colorectal cancer (CRC) risk and total dietary fat, saturated fat (SF), monounsaturated fat (MUFA) and polyunsaturated fat (PUFA) is inconsistent. Previous studies have used food frequency questionnaires (FFQ) to assess diet, but data from food diaries may be less prone to severe measurement error than data from FFQ. METHODS We conducted a case-control study nested within seven prospective UK cohort studies, comprising 579 cases of incident CRC and 1996 matched controls. Standardized dietary data from 4- to 7-day food diaries and from FFQ were used to estimate odds ratios for CRC risk associated with intake of fat and subtypes of fat using conditional logistic regression. We also calculated multivariate measurement error corrected odds ratios for CRC using repeated food diary measurements. RESULTS We observed no associations between intakes of total dietary fat or types of fat and CRC risk, irrespective of whether dietary data were obtained using food diaries or FFQ. CONCLUSION Our results do not support the hypothesis that intakes of total dietary fat, SF, MUFA or PUFA are linked to risk of CRC.

Self-reported and measured anthropometric data and risk of colorectal cancer in the EPIC-Norfolk study.

Background:Epidemiological studies have shown inconsistent results for the association between body size and colorectal cancer (CRC) risk. Inconsistencies may be because of the reliance on self-reported measures of body size.Objective:We examined the association of self-reported and directly assessed anthropometric data (body height, weight, body mass index (BMI), waist, hip, waist-to-hip ratio (WHR) and chest circumference) with CRC risk in the EPIC–Norfolk study.Design:A total of 20 608 participants with complete self-reported and measured height and weight and without any history of cancer were followed up an average of 11 years, during which 357 incident CRC cases were recorded. Hazard Ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.Results:After adjustment for confounders, HRs among women in the highest quintile of the body size measure relative to the lowest quintile showed that measured height (HR=1.98, 95% CI=1.19–3.28, P trend=0.009), measured waist circumference (HR=1.65, 95% CI=0.97–2.86, P trend=0.009) and measured WHR (HR=2.07, 95% CI=1.17–3.67, P trend=0.001) were associated with increased CRC risk. Associations using corresponding self-reported measures were attenuated and not statistically significant. Conversely, the association of BMI with CRC risk in women was weaker using measured BMI (HR=1.57, 95% CI=0.91–2.73, P trend=0.05) compared with self-reported BMI (HR=1.97, 95% CI=1.18–3.30, P trend=0.02). In men no significantly increased CRC risk was observed with any of the anthropometric measures.Conclusions:Measured height, waist circumference and WHR were associated with CRC risk in women, whereas any significant associations with those measures were attenuated when self-reported data were used.

Using surrogate biomarkers to improve measurement error models in nutritional epidemiology.

Nutritional epidemiology relies largely on self-reported measures of dietary intake, errors in which give biased estimated diet–disease associations. Self-reported measurements come from questionnaires and food records. Unbiased biomarkers are scarce; however, surrogate biomarkers, which are correlated with intake but not unbiased, can also be useful. It is important to quantify and correct for the effects of measurement error on diet–disease associations. Challenges arise because there is no gold standard, and errors in self-reported measurements are correlated with true intake and each other. We describe an extended model for error in questionnaire, food record, and surrogate biomarker measurements. The focus is on estimating the degree of bias in estimated diet–disease associations due to measurement error. In particular, we propose using sensitivity analyses to assess the impact of changes in values of model parameters which are usually assumed fixed. The methods are motivated by and applied to measures of fruit and vegetable intake from questionnaires, 7-day diet diaries, and surrogate biomarker (plasma vitamin C) from over 25000 participants in the Norfolk cohort of the European Prospective Investigation into Cancer and Nutrition. Our results show that the estimated effects of error in self-reported measurements are highly sensitive to model assumptions, resulting in anything from a large attenuation to a small amplification in the diet–disease association. Commonly made assumptions could result in a large overcorrection for the effects of measurement error. Increased understanding of relationships between potential surrogate biomarkers and true dietary intake is essential for obtaining good estimates of the effects of measurement error in self-reported measurements on observed diet–disease associations. Copyright