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Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence.

ABSTRACT: A new evaluation of previously published data suggested to us that the accumulation of mutations might slow, rather than increase, as individuals age. To explain this unexpected finding, we hypothesized that normal stem cell division rates might decrease as we age. To test this hypothesis, we evaluated cell division rates in the epithelium of human colonic, duodenal, esophageal, and posterior ethmoid sinonasal tissues. In all 4 tissues, there was a significant decrease in cell division rates with age. In contrast, cell division rates did not decrease in the colon of aged mice, and only small decreases were observed in their small intestine or esophagus. These results have important implications for understanding the relationship between normal stem cells, aging, and cancer. Moreover, they provide a plausible explanation for the enigmatic age-dependent deceleration in cancer incidence in very old humans but not in mice.

SUBMITTER: Tomasetti C

PROVIDER: S-EPMC6789572 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence.

Tomasetti Cristian C Poling Justin J Roberts Nicholas J NJ London Nyall R NR Pittman Meredith E ME Haffner Michael C MC Rizzo Anthony A Baras Alex A Karim Baktiar B Kim Antonio A Heaphy Christopher M CM Meeker Alan K AK Hruban Ralph H RH Iacobuzio-Donahue Christine A CA Vogelstein Bert B

Proceedings of the National Academy of Sciences of the United States of America 20190923 41

A new evaluation of previously published data suggested to us that the accumulation of mutations might slow, rather than increase, as individuals age. To explain this unexpected finding, we hypothesized that normal stem cell division rates might decrease as we age. To test this hypothesis, we evaluated cell division rates in the epithelium of human colonic, duodenal, esophageal, and posterior ethmoid sinonasal tissues. In all 4 tissues, there was a significant decrease in cell division rates wit ...[more]

PMID: 31548407

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Project description:BackgroundAlthough breast cancer incidence is higher in black women than in white women among women younger than 40 years, the reverse is true among those aged 40 years or older. This crossover in incidence rates between black and white ethnic groups has been well described, has not been completely understood, and has been viewed as an artifact.MethodsTo quantify this incidence rate crossover, we examined data for 440 653 women with invasive breast cancer from the National Cancer Institute's Surveillance, Epidemiology, and End Results database from January 1, 1975, through December 31, 2004. Data on invasive female breast cancers were stratified by race, age at diagnosis, year of diagnosis, and tumor characteristics. Standard descriptive analyses were supplemented with Poisson regression models, age-period-cohort models, and two-component mixture models. All statistical tests were two-sided.ResultsWe observed qualitative (ie, crossing or reversing) interactions between age and race. That is, age-specific incidence rates overall (expressed as number of breast cancers per 100 000 woman-years) were higher among black women (15.5) than among white women (13.1) younger than 40 years (difference = 2.4, 95% confidence interval [CI] = 2.4 to 2.4), and then, age-specific rates crossed with rates higher among white women (281.3) than among black women (239.5) aged 40 years or older (difference = 41.8, 95% CI = 41.7 to 41.9). The black-to-white incidence rate crossover was observed for all tumor characteristics assessed, although the crossover occurred at earlier ages of diagnosis for low-risk tumor characteristics than for high-risk tumor characteristics. The incidence rate crossover between ethnic groups was robust (ie, reliable and reproducible) to adjustment for calendar period and birth cohort effects in age-period-cohort models (P < .001 for difference by race).ConclusionAlthough this ecologic study cannot determine the individual-level factors responsible for the racial crossover in vital rates, it confirms that the age-related crossover in breast cancer incidence rates between black and white ethnic groups is a robust age-specific effect that is independent of period and cohort effects.

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Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence.

Publications

Cell division rates decrease with age, providing a potential explanation for the age-dependent deceleration in cancer incidence.

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