Elucidation of Factors Affecting the Age-Dependent Cancer Occurrence Rates.

Cancer occurrence rates exhibit diverse age-related patterns, and understanding them may shed new and important light on the drivers of cancer evolution. This study systematically analyzes the age-dependent occurrence rates of 23 carcinoma types, focusing on their age-dependent distribution patterns, the determinants of peak occurrence ages, and the significant difference between the two genders. According to the SEER reports, these cancer types have two types of age-dependent occurrence rate (ADOR) distributions, with most having a unimodal distribution and a few having a bimodal distribution. Our modeling analyses have revealed that (1) the first type can be naturally and simply explained using two age-dependent parameters: the total number of stem cell divisions in an organ from birth to the current age and the availability levels of bloodborne growth factors specifically needed by the cancer (sub)type, and (2) for the second type, the first peak is due to viral infection, while the second peak can be explained as in (1) for each cancer type. Further analyses indicate that (i) the iron level in an organ makes the difference between the male and female cancer occurrence rates, and (ii) the levels of sex hormones are the key determinants in the onset age of multiple cancer types. This analysis deepens our understanding of the dynamics of cancer evolution shared by diverse cancer types and provides new insights that are useful for cancer prevention and therapeutic strategies, thereby addressing critical gaps in the current paradigm of oncological research.