Gains in Statistical Power From Using a Dietary Biomarker in Combination With Self-reported Intake to Strengthen the Analysis of a Diet-Disease Association: An Example From CAREDS

A major problem in detecting diet-disease associations in nutritional cohort studies is measurement error in self-reported intakes, which causes loss of statistical power. The authors propose using biomarkers correlated with dietary intake to strengthen analyses of diet-disease hypotheses and to increase statistical power. They consider combining self-reported intakes and biomarker levels using principal components or a sum of ranks and relating the combined measure to disease in conventional regression analyses. They illustrate their method in a study of the inverse association of dietary lutein plus zeaxanthin with nuclear cataracts, using serum lutein plus zeaxanthin as the biomarker, with data from the Carotenoids in Age-Related Eye Disease Study (United States, 2001–2004). This example demonstrates that the combined measure provides higher statistical significance than the dietary measure or the serum measure alone, and it potentially provides sample savings of 8%–53% over analysis with dietary intake alone and of 6%–48% over analysis with serum level alone, depending on the definition of the outcome variable and the choice of confounders entered into the regression model. The authors conclude that combining appropriate biomarkers with dietary data in a cohort can strengthen the investigation of diet-disease associations by increasing the statistical power to detect them

Risk of breast cancer in young women in relation to body size and weight gain in adolescence and early adulthood

Findings have been inconsistent on effects of adolescent body size and adult weight gain on risk of breast cancer in young women. These relations were examined in a population-based case control study of 1590 women less than 45 years of age newly diagnosed with breast cancer during 1990–1992 in three areas of the US and an age-matched control group of 1390 women. Height and weight were measured at interview and participants asked to recall information about earlier body size. Logistic regression was used to estimate the relative risk of breast cancer adjusted for other risk factors. Women who were either much heavier or lighter than average in adolescence or at age 20 were at reduced risk. Weight gain after age 20 resulted in reduced risk, but the effect was confined to early-stage and, more specifically, lower grade breast cancer. Neither the risk reduction nor the variation by breast cancer stage or grade was explained by the method of cancer detection or by prior mammography history. These findings suggest that relations between breast cancer risk in young women and body weight at different ages is complex and that the risk reduction with adult weight gain is confined to less aggressive cancers. © 1999 Cancer Research Campaig

Validation of the MEDFICTS dietary questionnaire: A clinical tool to assess adherence to American Heart Association dietary fat intake guidelines

BACKGROUND: Dietary assessment tools are often too long, difficult to quantify, expensive to process, and largely used for research purposes. A rapid and accurate assessment of dietary fat intake is critically important in clinical decision-making regarding dietary advice for coronary risk reduction. We assessed the validity of the MEDFICTS (MF) questionnaire, a brief instrument developed to assess fat intake according to the American Heart Association (AHA) dietary "steps". METHODS: We surveyed 164 active-duty US Army personnel without known coronary artery disease at their intake interview for a primary prevention cardiac intervention trial using the Block food frequency (FFQ) and MF questionnaires. Both surveys were completed on the same intake visit and independently scored. Correlations between each tools' assessment of fat intake, the agreement in AHA step categorization of dietary quality with each tool, and the test characteristics of the MF using the FFQ as the gold standard were assessed. RESULTS: Subjects consumed a mean of 36.0 ± 13.0% of their total calories as fat, which included saturated fat consumption of 13.0 ± 0.4%. The majority of subjects (125/164; 76.2%) had a high fat (worse than AHA Step 1) diet. There were significant correlations between the MF and the FFQ for the intake of total fat (r = 0.52, P < 0.0001) and saturated fat (r = 0.52, P < 0.0001). Despite these modest correlations, the currently recommended MF cutpoints correctly identified only 29 of 125 (23.3%) high fat (worse than AHA Step 1) diets. Overall agreement for the AHA diet step between the FFQ and MF (using the previously proposed MF score cutoffs of 0–39 [AHA Step 2], 40–70 [Step 1], and >70 [high fat diet]) was negligible (kappa statistic = 0.036). The MF was accurate at the extremes of fat intake, but could not reliably identify the 3 AHA dietary classifications. Alternative MF cutpoints of <30 (Step 2), 30–50 (Step 1), and >50 (high fat diet) were highly sensitive (96%), but had low specificity (46%) for a high fat diet. ROC curve analysis identified that a MF score cutoff of 38 provided optimal sensitivity 75% and specificity 72%, and had modest agreement (kappa = 0.39, P < 0.001) with the FFQ for the identification of subjects with a high fat diet. CONCLUSIONS: The MEDFICTS questionnaire is most suitable as a tool to identify high fat diets, rather than discriminate AHA Step 1 and Step 2 diets. Currently recommended MEDFICTS cutpoints are too high, leading to overestimation of dietary quality. A cutpoint of 38 appears to be providing optimal identification of patients who do not meet AHA dietary guidelines for fat intake

Birth weight is associated with postmenopausal breast cancer risk in Swedish women

There is some evidence that birth weight is associated with breast cancer. Whether this association differs between premenopausal and postmenopausal ages is still unclear. The results from this study suggest that higher birth weight is a risk factor for postmenopausal breast cancer (OR 1.06, CI 1.00-1.12, per 100 g), independent of selected early-life and adult factors

Birth weight as a predictor of breast cancer: a case–control study in Norway

The hypothesis that birth weight is positively associated with adult risk of breast cancer implies that factors related to intrauterine growth may be important for the development of this malignancy. Using stored birth records from the two main hospitals in Trondheim and Bergen, Norway, we collected information on birth weight, birth length and placenta weight among 373 women who developed breast cancer. From the same archives, we selected as controls 1150 women of identical age as the cases without a history of breast cancer. Information on age at first birth and parity were collected from the Central Person Registry in Norway. Based on conditional logistic regression analysis, breast cancer risk was positively associated with birth weight and with birth length (P for trend=0.02). Birth weights in the highest quartile (3730 g or more) were associated with 40% higher risk (odds ratio, 1.4, 95% confidence interval, 1.1–1.9) of breast cancer compared to birth weights in the lowest quartile (less than 3090 g). For birth length, the odds ratio for women who were 51.5 cm or more (highest quartile) was 1.3 (95% confidence interval, 1.0–1.8) compared to being less than 50 cm (lowest quartile) at birth. Adjustment for age at first birth and parity did not change these estimates. Placenta weight was not associated with breast cancer risk. This study provides strong evidence that intrauterine factors may influence future risk of breast cancer. A common feature of such factors would be their ability to stimulate foetal growth and, simultaneously, to influence intrauterine development of the mammary gland

Breast cancer incidence in food- vs non-food-producing areas in Norway: possible beneficial effects of World War II

It has been suggested that World War II influenced breast cancer risk among Norwegian women by affecting adolescent growth. Diet changed substantially during the war, and the reduction in energy intake was assumed to be larger in non-food- producing than in food-producing municipalities. In the present study, we have looked at the influence of residential history in areas with and without food production on the incidence of breast cancer in a population-based cohort study consisting of 597 906 women aged between 30 and 64 years. The study included 7311 cases of breast cancer, diagnosed between 1964 and 1992. The risk estimates were calculated using a Poisson regression model. The results suggest that residential history may influence the risk of breast cancer, where the suggested advantageous effect of World War II seems to be larger in non-food-producing than in food-producing areas. Breast cancer incidence was observed to decline for the post-war cohorts, which is discussed in relation to diet

Adolescent diet and risk of breast cancer

BACKGROUND: Early life exposures, including diet, have been implicated in the etiology of breast cancer. METHODS: A nested case-control study was conducted among participants in the Nurses' Health Study who completed a 24-item questionnaire about diet during high school. There were 843 eligible cases diagnosed between onset of study (1976) and before the return of the high school diet questionnaire (1986), who were matched 10:1 with controls on the basis of age. RESULTS: Women who had, during adolescence, a higher consumption of eggs, vegetable fat and fiber had a lower risk of breast cancer, whereas risk of breast cancer was increased among women who consumed more butter. CONCLUSIONS: A possible association of elements of adolescent diet with risk of breast cancer is reported, but the findings require confirmation in prospective study