Estimation and interpretation of models of absolute risk from epidemiologic data, including family-based studies

Absolute risk is the chance that a person with given risk factors and free of the disease of interest at age a will be diagnosed with that disease in the interval (a, a + tau]. Absolute risk is sometimes called cumulative incidence. Absolute risk is a "crude" risk because it is reduced by the chance that the person will die of competing causes of death before developing the disease of interest. Cohort studies admit flexibility in modeling absolute risk, either by allowing covariates to affect the cause-specific relative hazards or to affect the absolute risk itself. An advantage of cause-specific relative risk models is that various data sources can be used to fit the required components. For example, case-control data can be used to estimate relative risk and attributable risk, and these can be combined with registry data on age-specific composite hazard rates for the disease of interest and with national data on competing hazards of mortality to estimate absolute risk. Family-based designs, such as the kin-cohort design and collections of pedigrees with multiple affected individuals can be used to estimate the genotype-specific hazard of disease. Such analyses must be adjusted for ascertainment, and failure to take into account residual familial risk, such as might be induced by unmeasured genetic variants or by unmeasured behavioral or environmental exposures that are correlated within families, can lead to overestimates of mutation-specific absolute risk in the general population.