Selected Articles from This Issue

To date there have been limited data that demonstrate the potential reduction of invasive cancer through interception of preneoplastic lesions (PNL). To understand this impact at a population level, Pradhan and colleagues estimated the hypothetical number of invasive cancers that could be avoided in the US population by the interception of PNL. Analysis suggested that a substantial number of invasive cancer cases could be avoided through detection and interception of PNL. Positive predictive value and negative predictive value estimates confirm that avoidability of invasive cancer among PNL is dependent on PNL prevalence and percent progression per year. These results may guide research and implementation of studies intended to maximize the number of invasive cancers that can be avoided by PNL interception.For biomarkers that have shown potential relevance to cancer screening based on case–control studies, there is a critical need for further validation in biospecimens collected through prospective screening studies conducted in an intended-use population with diverse backgrounds. The Lung Cancer, Early Detection, Assessment of Risk, and Prevention (LEAP) study was designed to address such needs through an international prospective cohort study in which participants received low-dose CT screening and provided repeated blood samples with continued longitudinal follow-up for accurate determination of cancer diagnoses. Here, Dennison and colleagues present the design, the implementation, and results of the active screening phase of the LEAP study as well as the biospecimen and imaging repository available for biomarker validation.While there is evidence that Fusobacterium spp. in colon tissue is associated with prognosis, epidemiological data on the association between antibody response to different antigens produced by fusobacteria and colorectal cancer–specific mortality is lacking. Michaud and colleagues examined the relation to colorectal cancer–specific mortality using antibody responses previously measured for different antigens present in the F. nucleatum strain ATCC 25586, using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). While null overall, this is the first study to observe an association between antibody response to fusobacteria and colorectal cancer–specific mortality among individuals with earlier onset colorectal cancer. Future studies are needed to confirm these findings and understand the role of systemic antibody responses to fusobacteria in cancer.Analyses of etiologic heterogeneity use molecular markers to subtype cancers and test whether an exposure is more strongly associated with one tumor subtype as opposed to other subtypes. However, these molecular markers may best be conceptualized as mediators of exposure–disease relationships. Seven model causal scenarios, based on data from the literature on postmenopausal breast cancer, were created with varying relationships between an exposure, a mediating or non-mediating molecular marker, and a disease status, with molecular marker used to subtype the disease. Mooney and Rundle assessed how well the analyses of etiologic heterogeneity identify the distinct etiologic pathways. Results indicate that analyses of etiologic heterogeneity cannot distinguish between the modeled causal scenarios when a mediating or non-mediating molecular marker is used to subtype tumors.