Evaluating the Number of Stages in Development of Squamous Cell and Adenocarcinomas across Cancer Sites Using Human Population-Based Cancer Modeling

BACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages) were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype being more strongly associated with ACs/SCCs histotype than with organ/site

Phenotypic Aspects of Longevity

Centenarians are individuals who live over the average life span characteristic of their population. The growing number of old people worldwide makes it necessary to identify a good strategy to reach healthy ageing and avoid or delay age-related diseases. The longevity phenotype is the result of a positive combination between genetic, epigenetic, stochastic and lifestyle factors. So, the analysis of all the known parameters that can influence these single elements or their interaction can give new possible elements to delineate a sort of longevity signature. Starting from the easiest biomarkers as the haematochemical values and reaching the study of molecular and cellular components, as the pool of immune cells and their role in immunosenescence, it is possible to understand potential common elements between centenarians, so possible strategy to attain longevity or healthy life span. The mechanisms involved in the pathogenesis of age-related diseases, as the pro- and anti-inflammatory pathways or the pro- and antioxidant systems and their contribution, are crucial to this aim. Moreover, the psychological and cognitive aspects must be taken into account. In this chapter, to understand the phenotypic aspects of longevity, some aspects of centenarian phenotype, as example of positive biology, will be summarized