Variation in cancer risk between organs can not be explained by the degree of somatic clonal expansion

Abstract

Somatic clonal expansion refers to the proliferation and expansion of a cell clone within a multicellular organism. Since cancer also results from the uncontrolled proliferation of few cell clones, it is generally believed that aging-associated somatic clonal expansion observed in normal tissues represents a precancerous condition. For instance, hematological malignancy is often preceded by clonal hematopoiesis. However, the precise connection between cancer and somatic clonal expansion remains elusive in solid organs. In this study, we utilized a straightforward method to assess the relative quantitative degrees of clonal expansion in nine human organs. Our findings reveal that the degree of clonal expansion varies across different organs while remaining consistent among different individuals. Contrary to the general belief, we did not identify any significant correlation between lifetime cancer risk and the degree of lifetime somatic clonal expansion. For example, the lifetime risk of colorectal cancer is approximately 20 times higher than that of esophageal cancer, yet the former exhibited the lower degree of clonal expansion than the latter. Our results suggest that somatic clonal expansion represents an evolutionary process distinct from carcinogenesis in normal tissues, providing novel perspectives on precancerous conditions.