Cohort profile: the CARTaGENE Cohort Nutrition Study (Quebec, Canada).

PURPOSE: To address emerging nutritional epidemiological research questions, data from contemporary cohorts are needed. CARTaGENE is the largest ongoing prospective cohort study of men and women in Québec, Canada. Dietary information was collected making it a rich resource for the exploration of diet in the aetiology of many health outcomes. PARTICIPANTS: CARTaGENE recruited over 43 000 men and women aged 40-69 in two phases (A and B). In phase A, a total of 19 784 men and women were enrolled between 2009 and 2010. In 2011-2012, phase A participants of CARTaGENE were recontacted and invited to complete the self-administered Canadian Diet History Questionnaire II, which assessed usual intake over the past 12 months of a comprehensive array of foods, beverages and supplements; 9379 participants with non-missing age and sex data and with plausible total energy intake comprise the CARTaGENE Cohort Nutrition Study (4212 men; 5167 women). FINDINGS TO DATE: Available dietary data include intake of total energy, macronutrients and micronutrients, food group equivalents and a measure of diet quality based on the Canadian Healthy Eating Index 2005 (C-HEI 2005). Intake and diet quality varied among participants though they generally met the recommended dietary reference intakes for most nutrients. The mean C-HEI 2005 score was 61.5 (SD=14.0; max score=100), comparable to the general Canadian population. The mean (SD) scores for men and women separately were 57.0 (14.1) and 65.2 (12.8), respectively. C-HEI scores were higher for never smokers (61.6), those who had attained more than a high school education (61.4) and those with high physical activity (60.4) compared with current smokers (55.8), less than high school education level (56.2) and low physical activity (57.6), respectively (p values<0.01). FUTURE PLANS: The CARTaGENE Cohort Nutrition Study is an additional resource of the CARTaGENE platform and is available internationally to examine research questions related to diet and health among contemporary populations. Starting in 2024, annual diet assessments using two 24-hour dietary recalls over a 30-day period will take place, further expanding the cohort as a resource for dietary research.

Predicted 25-hydroxyvitamin D over the adult life and the risk of ovarian cancer.

The evidence from previous studies of serum 25-hydroxyvitamin D [25(OH)D] and ovarian cancer risk are not conclusive. However, 25(OH)D was generally only measured in late adulthood, which may not capture the etiologically relevant exposure periods. We investigated predicted 25(OH)D over the adult lifetime in relation to ovarian cancer risk in a population-based case-control study conducted from 2011 to 2016 in Montreal, Canada (490 cases, 896 controls). Predicted 25(OH)D was computed using previously validated regression models. Unconditional multivariable logistic regression models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for average predicted 25(OH)D over the adult life and risk. In addition, the relative importance of different periods of past 25(OH)D exposure was explored using a weighted cumulative exposure (WCE) model. For each 20 nmol/L increase in average predicted 25(OH)D over the adult life, the aOR (95% CI) was 0.73 (0.55-0.96). In WCE analyses, the inverse association was strongest for exposures 5 to 20 years and 35 to 55 years prior to diagnosis, with aORs (95% CIs) of 0.82 (0.69-0.94) and 0.79 (0.66-1.02), respectively, for each 20 nmol/L increase in predicted 25(OH)D. These results support an inverse association between 25(OH)D in adulthood and ovarian cancer risk.

An empirical evaluation of approximate and exact regression-based causal mediation approaches for a binary outcome and a continuous or a binary mediator for case-control study designs.

BACKGROUND: In the causal mediation analysis framework, several parametric regression-based approaches have been introduced in past years for decomposing the total effect of an exposure on a binary outcome into a direct effect and an indirect effect through a target mediator. In this context, a well-known strategy involves specifying a logistic model for the outcome and invoking the rare outcome assumption (ROA) to simplify estimation. Recently, exact estimators for natural direct and indirect effects have been introduced to circumvent the challenges prompted by the ROA. As for the approximate approaches relying on the ROA, these exact approaches cannot be used as is on case-control data where the sampling mechanism depends on the outcome. METHODS: Considering a continuous or a binary mediator, we empirically compare the approximate and exact approaches using simulated data under various case-control scenarios. An illustration of these approaches on case-control data is provided, where the natural mediation effects of long-term use of oral contraceptives on ovarian cancer, with lifetime number of ovulatory cycles as the mediator, are estimated. RESULTS: In the simulations, we found few differences between the performances of the approximate and exact approaches when the outcome was rare, both marginally and conditionally on variables. However, the performance of the approximate approaches degraded as the prevalence of the outcome increased in at least one stratum of variables. Differences in behavior were also observed among the approximate approaches. In the data analysis, all studied approaches were in agreement with respect to the natural direct and indirect effects estimates. CONCLUSIONS: In the case where a violation of the ROA applies or is expected, approximate mediation approaches should be avoided or used with caution, and exact estimators favored.