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Histopathological imaging has been routinely conducted in cancer diagnosis and recently used for modeling other cancer outcomes/phenotypes such as prognosis. Clinical/environmental factors have long been extensively used in cancer modeling. However, there is still a lack of study exploring possible interactions of histopathological imaging features and clinical/environmental risk factors in cancer modeling. In this article, we explore such a possibility and conduct both marginal and joint interaction analysis. Novel statistical methods, which are "borrowed" from gene⁻environment interaction analysis, are employed. Analysis of The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) data is conducted. More specifically, we examine a biomarker of lung function as well as overall survival. Possible interaction effects are identified. Overall, this study can suggest an alternative way of cancer modeling that innovatively combines histopathological imaging and clinical/environmental data.

Histopathological Imaging–Environment Interactions in Cancer Modeling