Cancer
The early-onset cancer epidemics: novel role of mixed methods research using the prospective cohort incident-tumor biobank method Shuji Ogino* Shuji Ogino Satoko Ugai Tsuyoshi Hamada Tomotaka Ugai
Early-onset cancer (EOC), generally defined as cancer diagnosed in adults under the age of 50 years, has shown increasing incidence in many parts of the world since the 1990s. Influences of decades-long risk factor exposures are suspected to contribute to the widespread rise of EOC in many organ systems. Current EOC research has a substantial gap between long-term exposure assessments and tumoral molecular/microenvironmental profiling. This is because a prospective cohort study, which typically enrolled middle-aged participants to have enough incident cancer cases during follow-up, may lack enough incident EOC cases in a given organ for tumor tissue profiling. To address this gap, we have developed a step-by-step “mixed-methods” approach, leveraging the prospective cohort incident-tumor biobank method (PCIBM) (Figure). The Figure also provides a proof-of-principle study example, using tumor cell LINE-1 DNA hypomethylation as a feature of early-onset colorectal cancer (CRC). The first step is to recognize that features of EOC in a given organ overlap with a later-onset cancer counterpart and that existing knowledge and new research on all-age cancers are useful for a better understanding of EOC. Second, EOC tumoral features are discovered and replicated. Third, the PCIBM examines long-term exposure variables and the incidence of all-age cancer (in a given organ) subtypes that possess tumoral features of EOC in the organ. Fourth, possibly in the future, identified putative risk factors will be tested for the incidence of EOC (in that organ) overall and subtypes that possess EOC tumoral features. This step-by-step mixed methods approach (even only up to the third step) enables us to better understand EOC etiologies when there are not enough incident EOC cases in a given organ with tumor profiling data in a prospective cohort study that has precious data on long-term exposure variables.
