Bimodal Age Distribution in Cancer Incidence

Abstract

Cancer is caused by accumulation of genetic changes which include activation of protooncogenes and loss of tumor suppressor genes. The age-specific incidence of cancer in general increases with advancing age. However, some cancers exhibit a bimodal distribution. Commonly recognized cancers with bimodal age distribution include acute lymphoblastic leukemia, osteosarcoma, Hodgkin's lymphoma, germ cell tumors and breast cancer. Delayed infection hypothesis has been used to provide explanation for the early childhood peak in leukemias and lymphomas, whereas the peak at an older age is associated with accumulation of protooncogenes and weakened immune system. Further genetic analysis and histopathological variations point to distinctly different cancers, varying genetically and histologically, which are often combined under a single category of cancers. Tumor characteristics and age distribution of these cancers varies also by population groups and has further implications on cancer screening methods. Although significant advances have been made to explain the bimodal nature of such cancers, the specific genetic mechanisms for each age distribution remain to be elucidated. Further distinction among the different cancer subtypes may lead to improvements in individual risk assessments, prevention and enhancement of treatment strategies.

From Bimodal to Unimodal: The Transformed Incidence of Osteosarcoma in the United States

“…This is attributable to an increase in activity at the metaphyseal plates leading to the rapid increase in growth that occurs around the time of puberty. 2,6,12 Furthermore, the most common sites for osteosarcoma are the distal femur, proximal tibia, and proximal humerus, which are all long bones that grow significantly during puberty. 4,6 This further reinforces the idea that osteosarcoma may be associated with increased activity at the metaphysis of bones, supporting the original theories proposed by Price.…”

“…We conducted a Fisher's exact test for each calendar year in the SEER data, assessing if there was a significant difference between the occurrence of osteosarcoma in patients 35-64 years old versus those 65+ years old (the age group classically described as constituting the second peak). [3][4][5][6][7] The p-values and odds ratio for each test across the 46 calendar year period were assessed for chronological trends over time. Statsmodel Version 0.13.5 in Python was used to conduct the Fisher's exact test with the significance level set at 0.05.…”

“…1 It is conventionally described as having a bimodal incidence by age, with the first mode in the teenage years and the second mode after 65 years of age. [2][3][4][5][6][7] We sought to examine the current age distribution for the incidence of osteosarcoma. We used two large United States specific health databases: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program which collects data on cancer incidence from various cancer registries, serving about 47.9 percent of the U.S. Population, and The National Inpatient Sample (NIS) dataset (Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality), which is the largest publicly available database of inpatient discharge data in the country.…”

Chondroblastic osteosarcoma

“…It has a bimodal presentation, with most cases between the ages of 14 and 18 years and a second smaller peak in older adults. 2 The gross cut surface depends on the type and degree of mineralization of the predominant matrix, which may be dense, solid, tan-white, resembling cortical bone or grey, rubbery or mucoid in the case of cartilaginous component. 3 Histomorphological diagnosis of osteosarcoma warrants the demonstration of neoplastic bone formation, which may be in any amount to render the diagnosis.…”