Association between TP53 mutations and the aging-related rise in cancer incidence rates

TP53's role as guardian of the genome diminishes with age, as the probability of mutation increases. Previous studies have shown an association between TP53 mutation and cancer. However, the role of TP53 mutation in the steep rise in cancer rates with aging has not been investigated at a population level. This relationship was quantified using the International Agency for Research on Cancer (IARC) TP53 and GLOBOCAN cancer databases. The power function exponent of the cancer rate was calculated for 5-year age-standardized incidence or mortality rates for up to 25 cancer sites occurring in adults of median age 42 to 72 years old. Linear regression analysis of the mean percentage of a cancer's TP53 mutations and the corresponding cancer exponent was conducted for four populations: worldwide, Japan, Western Europe, and the United States. Significant associations (p ≤ 0.05) were found for incidence rates but not mortality rates. Regardless of the population studied, positive associations were found for all cancer sites, with more significant associations for solid tumors, excluding sex-related tumors. For the United States, a significant association was apparent only when analysis utilized the Surveillance, Epidemiology, and End Results (SEER) database. This study found that TP53 mutations accounts for approximately one-fifth of the aging-related rise in the incidence of all cancers, and for one-third of solid tumors, in both instances excluding sex-related tumors. When applying the Bradford-Hill criteria for causality to the published literature on TP53 and cancer, plus the weak but significant associations between TP53 mutations and the rapid rise in cancer incidence with aging, they in sum support a causal role. (author)