Colorectal cancer incidence trends in the United States and United kingdom: evidence of right- to left-sided biological gradients with implications for screening.
Several lines of evidence support the premise that screening colonoscopy reduces colorectal cancer (CRC) incidence, but there may be differential benefits for right- and left-sided tumors. To better understand the biological basis of this differential effect, we derived biomathematical models of CRC incidence trends in U.S. and U.K. populations, representing relatively high- and low-prevalence screening, respectively. Using the Surveillance Epidemiology and End Results (SEER) and the Office for National Statistics (ONS) registries (both 1973-2006), we derived stochastic multistage clonal expansion (MSCE) models for right-sided (proximal colon) and left-sided (distal colon and rectal) tumors. The MSCE concept is based on the initiation-promotion-progression paradigm of carcinogenesis and provides a quantitative description of natural tumor development from the initiation of an adenoma (via biallelic tumor suppressor gene inactivation) to the clinical detection of CRC. From 1,228,036 (SEER: 340,582; ONS: 887,454) cases, parameter estimates for models adjusted for calendar-year and birth-cohort effects showed that adenoma initiation rates were higher for right-sided tumors, whereas, paradoxically, adenoma growth rates were higher for left-sided tumors. The net effect was a higher cancer risk in the right colon only after age 70 years. Consistent with this finding, simulations of adenoma development predicted that the relative prevalence for right- versus left-sided tumors increases with increasing age, a differential effect most striking in women. Using a realistic biomathematical description of CRC development for two nationally representative registries, we show age- and sex-dependent biological gradients for right- and left-sided colorectal tumors. These findings argue for an age-, sex-, and site-directed approach to CRC screening.
Centre for Disease Control, University of British Columbia, Vancouver, Canada. rmeza@fhcrc.org
Rafael
R
Meza
Jihyoun
J
Jeon
Andrew G
AG
Renehan
E Georg
EG
Luebeck
D000236:Adenoma / Q000453:epidemiology / Q000473:pathology; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D008954:Models, Biological; D012042:Registries; D018426:SEER Program; D012737:Sex Factors; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055815:Young Adult