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.

[1]  B. Boman,et al.  Human colon cancer stem cells: a new paradigm in gastrointestinal oncology. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  P. Pinsky.  A multi-stage model of adenoma development. , 2000, Journal of theoretical biology.

[3]  J. Dick,et al.  A human colon cancer cell capable of initiating tumour growth in immunodeficient mice , 2007, Nature.

[4]  L. Rabeneck,et al.  Association of Colonoscopy and Death From Colorectal Cancer , 2009, Annals of Internal Medicine.

[5]  P. Maisonneuve,et al.  Smoking and colorectal cancer: a meta-analysis. , 2008, JAMA.

[6]  Linda Rabeneck,et al.  Rates of new or missed colorectal cancers after colonoscopy and their risk factors: a population-based analysis. , 2007, Gastroenterology.

[7]  Paul Marjoram,et al.  Inferring clonal expansion and cancer stem cell dynamics from DNA methylation patterns in colorectal cancers , 2009, Proceedings of the National Academy of Sciences.

[8]  Xiaocheng Wu,et al.  Subsite-specific colorectal cancer incidence rates and stage distributions among Asians and Pacific Islanders in the United States, 1995 to 1999. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[9]  Syed G. Shah,et al.  Magnetic imaging of colonoscopy: an audit of looping, accuracy and ancillary maneuvers. , 2000, Gastrointestinal endoscopy.

[10]  K. Machens,et al.  Estrogen plus progestin and colorectal cancer in postmenopausal women. , 2004, The New England journal of medicine.

[11]  E. Luebeck,et al.  Gestational mutations and carcinogenesis. , 2005, Mathematical biosciences.

[12]  E. Riboli,et al.  Alcohol intake and colorectal cancer risk: A dose–response meta‐analysis of published cohort studies , 2007, International journal of cancer.

[13]  S. Sadahiro,et al.  Analysis of length and surface area of each segment of the large intestine according to age, sex and physique , 2005, Surgical and Radiologic Anatomy.

[14]  D A Johnson,et al.  A prospective study of the prevalence of colonic neoplasms in asymptomatic patients with an age-related risk. , 1990, The American journal of gastroenterology.

[15]  S. Roberts,et al.  Measurement of in vivo proliferation in human colorectal mucosa using bromodeoxyuridine. , 1992, Gut.

[16]  E Georg Luebeck,et al.  Multistage carcinogenesis and the incidence of colorectal cancer , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Jihyoun Jeon,et al.  Age-specific incidence of cancer: Phases, transitions, and biological implications , 2008, Proceedings of the National Academy of Sciences.

[18]  J. Habbema,et al.  A novel hypothesis on the sensitivity of the fecal occult blood test , 2009, Cancer.

[19]  C D Langefeld,et al.  Colonic neoplasia in asymptomatic persons with negative fecal occult blood tests: influence of age, gender, and family history. , 1993, The American journal of gastroenterology.

[20]  Hans Clevers,et al.  Crypt stem cells as the cells-of-origin of intestinal cancer , 2009, Nature.

[21]  F. C. Lucibello,et al.  Localization of the gene for familial adenomatous polyposis on chromosome 5 , 1987, Nature.

[22]  P. Foutch,et al.  Prevalence and malignant potential of colorectal polyps in asymptomatic, average-risk men. , 1991, The American journal of gastroenterology.

[23]  B. Rowlands,et al.  Variability of cell proliferation in the proximal and distal colon of normal rats and rats with dimethylhydrazine induced carcinogenesis. , 2002, World journal of gastroenterology.

[24]  T. Reilly,et al.  Lifestyle factors and colorectal cancer risk (2): a systematic review and meta‐analysis of associations with leisure‐time physical activity , 2009, Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland.

[25]  D. Ransohoff,et al.  How Much Does Colonoscopy Reduce Colon Cancer Mortality? , 2009, Annals of Internal Medicine.

[26]  P. Loehrer.  Relation Between Medicare Screening Reimbursement and Stage at Diagnosis for Older Patients With Colon Cancer , 2008 .

[27]  D. Lieberman,et al.  Prevalence of colon polyps detected by colonoscopy screening in asymptomatic black and white patients. , 2008, JAMA.

[28]  H. El‐Serag,et al.  Is There a True “shift” to the Right Colon in the Incidence of Colorectal Cancer? , 2003, American Journal of Gastroenterology.

[29]  D. Ransohoff,et al.  Results of screening colonoscopy among persons 40 to 49 years of age. , 2002, The New England journal of medicine.

[30]  H. Brenner,et al.  Expected reduction of colorectal cancer incidence within 8 years after introduction of the German screening colonoscopy programme: estimates based on 1,875,708 screening colonoscopies. , 2009, European journal of cancer.

[31]  T. Reilly,et al.  Lifestyle factors and colorectal cancer risk (1): systematic review and meta‐analysis of associations with body mass index , 2009, Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland.

[32]  B. Iacopetta.  Are there two sides to colorectal cancer? , 2002, International journal of cancer.

[33]  Martin A. Nowak,et al.  Comparative lesion sequencing provides insights into tumor evolution , 2008, Proceedings of the National Academy of Sciences.

[34]  H. Brenner,et al.  Should colorectal cancer screening start at the same age in European countries? Contributions from descriptive epidemiology , 2008, British Journal of Cancer.

[35]  M. Goodman,et al.  Secular changes in colorectal cancer incidence by subsite, stage at diagnosis, and race/ethnicity, 1992–2001 , 2006, Cancer.

[36]  C. Ulrich,et al.  Does Folic Acid Supplementation Prevent or Promote Colorectal Cancer? Results from Model-Based Predictions , 2008, Cancer Epidemiology Biomarkers & Prevention.

[37]  Justice Jw,et al.  CANCER SCREENING PROGRAM. , 1964 .

[38]  Charles J. Kahi,et al.  Effect of screening colonoscopy on colorectal cancer incidence and mortality. , 2009, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[39]  D. Lieberman,et al.  Screening for colon malignancy with colonoscopy. , 1991, The American journal of gastroenterology.

[40]  A. Sonnenberg,et al.  Protection by endoscopy against death from colorectal cancer. A case-control study among veterans. , 1995, Archives of internal medicine.

[41]  J. Reguła,et al.  Colonoscopy in colorectal-cancer screening for detection of advanced neoplasia. , 2006, The New England journal of medicine.

[42]  S. Sadahiro,et al.  Relationship between length and surface area of each segment of the large intestine and the incidence of colorectal cancer , 1991, Cancer.

[43]  S. Altschul,et al.  Identification of FAP locus genes from chromosome 5q21. , 1991, Science.

[44]  D. Lieberman,et al.  Colonoscopy practice patterns since introduction of medicare coverage for average-risk screening. , 2004, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[45]  E. Luebeck,et al.  Evaluation of screening strategies for pre-malignant lesions using a biomathematical approach. , 2008, Mathematical biosciences.

[46]  W. Zoller,et al.  [Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer]. , 2001, Zeitschrift fur Gastroenterologie.

[47]  L M Schuman,et al.  Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. , 1993, The New England journal of medicine.

[48]  J. Jass.  Classification of colorectal cancer based on correlation of clinical, morphological and molecular features , 2007, Histopathology.