Table 3.
Important considerations in the design of EC urinary biomarker studies.
| Considerations | Role in EC pathogenesis and risk | Effect on urine biomarker research | Control strategy |
|---|---|---|---|
| Age | EC is a disease of the elderly, 2/3rd of all cases are diagnosed between ages 50 and 74 (14) | Age related changes in urinary protein excretion. Several metabolites are linked to the ageing process (71) | Age group eligibility criteria Balance in age distribution between cases and controls Co-variant analysis (42) |
| Diet | Evidence linking diet and brewed drinks including isoflavone (soy), coffee, and tea to EC risk (10). Possibility of differential use between cases and controls. | Exogenous source of metabolites, prone to individual variability, can confound biomarker findings (42). | Urine collection after an overnight fast Co-variant analysis (42) |
| Medications | Use of medications linked to conditions that can increase EC risk such as hypertension may systematically differ between EC cases and controls (14, 72), | Linked to urinary protein and metabolic profile. Anti-hypertensive can influence urinary proteome (73), thus confounding biomarker findings, individual variability in their use (42). | Urine collection before specific drug intake on the day if feasible, Asking participants to withhold drug use temporarily if feasible Exclusion of drug related metabolites during analysis Co-variant analysis |
| Physical activity level/BMI | High levels of physical activity reduces EC risk (10). High BMI increases risk of EC (70). Possibility of differential BMI between EC cases and controls |
Urinary metabolic markers of adiposity likely to differ between cases and controls (74). Physical activity impacts on urinary protein levels. |
Co-variant analysis (42). Exclusion of urinary markers of adiposity Balance in median BMI between study arms |
| Menopausal status | EC is mostly a post-menopausal disease (28) | Hormone altering conditions like menopause may influence urine metabolic profiles (42) | Exclusion of pre-menopausal women Balance in proportion of pre/postmenopausal women between cases and controls. Co-variant analysis (28) |
| Smoking | Smoking reduces EC risk (10). Possibility of differential use between cases and controls. | Urinary nicotine metabolites (75) may differ between EC cases and controls | Co-variant analysis (42) Balance in proportion of smokers in study arms Exclusion of nicotine metabolites. |
| Geographical location | EC is more common in Western countries compared to developing countries. Important in cross-national studies | Geographical variation in lifestyle factors that can influence urinary metabolic and urinary profiles (42). | Urine collection from participants from a homogenous region. Co-variant analysis (42) |
| Seasonal effects | Not applicable | Evidence of seasonal effects of diet, lifestyle and exercise patterns on metabolic urinary profiles (42). | Urine collection at a specific time of the year and not all year round (42). Co-variant analysis |