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FACET - European Journal of Cancer Care March 2004. Genetics of colorectal cancer Rafi, I. 1. Ascertainment Good family history Use of computers Questionnaire. Slide One. *Click on “View”; “Notes Page” for explanatory notes. slides available at: www.blackwellpublishing.com/journals/ecc. - PowerPoint PPT Presentation
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FACET - European Journal of Cancer CareMarch 2004
slides available at: www.blackwellpublishing.com/journals/ecc
Genetics of colorectal cancerRafi, I.1
Slid
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ne
*Click on “View”; “Notes Page” for explanatory notes
Ascertainment
• Good family history
• Use of computers
• Questionnaire
FACET - European Journal of Cancer CareMarch 2004
slides available at: www.blackwellpublishing.com/journals/ecc
Genetics of colorectal cancer(continued)
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wo
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Primary-Secondary Care
Communication between primary care and secondary care is important in the management of families at high genetic risk.
• Filter low risk families
• CMO report 1996
• GP’s may overestimate
risk
FACET - European Journal of Cancer CareMarch 2004
slides available at: www.blackwellpublishing.com/journals/ecc
Genetics of colorectal cancer(continued)
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hre
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Epidemiology In England and Wales, colorectal cancer is the second most common cause of cancer death.
• Rising incidence
The age-standardised incidence rates for colon cancer are:
• 17.1 per 100,000 for males
• 13.2 per 100,000 for females
• Ethnic variation
• Social class influence
FACET - European Journal of Cancer CareMarch 2004
slides available at: www.blackwellpublishing.com/journals/ecc
Genetics of colorectal cancer(continued)
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Aetiology
15-20% of cases of colorectal cancer are accounted for by genetic causes whilst 80-85% of cases of colorectal cancer are sporadic, arising from pre-malignant adenomatous polyps.
• Pre-existing adenomas
• Several genetic
abnormalities and genes
involved
• Environment-genetic
interplay
FACET - European Journal of Cancer CareMarch 2004
slides available at: www.blackwellpublishing.com/journals/ecc
Genetics of colorectal cancer(continued)
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Screening
• Do relatives of an
affected individual with
colorectal cancer have a
greater lifetime risk
compared to normal
population?
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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ix
*Click on “View”; “Notes Page” for explanatory notes
Screening/outcomes
• Mortality
• Type of screening
• Evidence base
• Targeted v general
population
slides available at: www.blackwellpublishing.com/journals/ecc
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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Genetic Families at Risk
• Familial Adenomatous
Polyposis (FAP)
• Hereditary Non-Polyposis
Coli (HNPCC)
• Familial Colorectal Cancer
(FCC)
slides available at: www.blackwellpublishing.com/journals/ecc
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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Familial Adenomatous
Poylposis
• Germ-line mutations in
the APC gene
• Undifferentiated growth of
adenomas
• Extra-colonic
manifestations
slides available at: www.blackwellpublishing.com/journals/ecc
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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HNPCC
• Mutation in genes
essential for DNA
mismatch repair
• Right sided colonic
tumours
• Extra colonic cancers
such as endometrial,
ovarian, bladder and
renal tumours
slides available at: www.blackwellpublishing.com/journals/ecc
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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Familial
Families have an increased
lifetime risk of developing
colorectal cancer where there
is a first-degree relative with
colorectal cancer.
Risk stratification based on:
• Number of first degree
relatives affected
• Early age of cancers
slides available at: www.blackwellpublishing.com/journals/ecc
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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*Click on “View”; “Notes Page” for explanatory notes
slides available at: www.blackwellpublishing.com/journals/ecc
Genetic epidemiology
Lovett’s incidence and
cancer mortality study
elicited family histories of
patients admitted to St
Mark’s Hospital (London) for
treatment for colorectal
cancer.
• Life tables method
• Identifying risks to
members of colorectal
cancer families
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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Genetic Studies
• Burt (1996)
• St John et al (1993)
• Utah population data
(1994)
slides available at: www.blackwellpublishing.com/journals/ecc
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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Lifetime risk
Houlston et al (1990) estimated the risks to relatives of patients with colorectal cancer using Lovett’s pedigrees of families.
• Population risk – 1 in 50
• One relative affected – 1 in 17
• One first degree/one second degree – 1 in 12
• One relative under 45 – 1 in 10
• Two first degree relatives
slides available at: www.blackwellpublishing.com/journals/ecc
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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*Click on “View”; “Notes Page” for explanatory notes
slides available at: www.blackwellpublishing.com/journals/ecc
Screening methods (1)
• FAP
• Sigmoidoscopy (starting
in adolescence)
• Gastro-duodenoscopy
• Gene testing for the APC
gene
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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*Click on “View”; “Notes Page” for explanatory notes
slides available at: www.blackwellpublishing.com/journals/ecc
Screening methods (2)
• HNPCC
• Colonoscopy
• ? Pelvic Ultrasound
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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*Click on “View”; “Notes Page” for explanatory notes
slides available at: www.blackwellpublishing.com/journals/ecc
Screening by genetic testing
• Genetic counselling
• The role of genetic testing in patients with suspected hereditary colorectal cancer is to:
• Determine if affected patient is carrier of germ-line mutation of one of the colorectal genes
• Allow screening of other family members through genetic testing alone
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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slides available at: www.blackwellpublishing.com/journals/ecc
Conclusion
• Evidence that screening
affects mortality is
sparse
• Further research
• Need for clear referral
criteria
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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slides available at: www.blackwellpublishing.com/journals/ecc
References • Bodmer WF, Failey CJ, Bodmer J, et al.
(1987) Localisation of the gene for familial adenomatous polyposis on chromosome 5. Nature, 328:614-616.
• Burt R. (1996) Familial risk and colon cancer. International Journal of Cancer 69:44-46.
• Department of Health. (1996) Genetics and Cancer Services Report of a working group for the Chief Medical officer. DOH.
• Department of Health. (1995b) Report of the genetics research advisory group (first report of the NHS central research and development committee on the new genetics).
• Emery J, Walton R, Murphy M, et al. (2000) Computer support for interpreting family histories of breast and ovarian cancer in primary care : comparative study with simulated cases. British Medical Journal, 321:28-32.
• Emery J, Watson E, Rose P, et al. (1999) A systematic review of the literature exploring the role of primary care in genetic services. Family Practice, 16, No 4:426-445.
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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References (continued)• Houlston RS, Murday V, Harocopes C, et al.
(1990) Screening and genetic counselling for relatives of patients with colorectal cancer in a family cancer clinic. British Medical Journal, 301:366-368.
• House W, Sharp D and Sheridan E. (1999) Identifying and screening patients at high risk of colo-rectal cancer in general practice. Journal of Medical Screening, 6(4):205-208.
• Leggat V, Mackay J, Marteau T, et al. (2000) The psychological impact of a cancer family history questionnaire completed in general practice. Journal of Medical Genetics, 37:470-472.
• Leggat V, Mackay J, and Yates JRW. (1999) Evaluation of questionnaire on cancer family history in identifying patients at increased genetic risk in general practice. British Medical Journal, 319:757-758.
• Lovett E. (1976a) Familial cancer of the gastro-intestinal tract. British Journal of Surgery, 63:19-22.
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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References (continued)• Lovett E. (1976b) Family studies in cancer
of the colon and rectum. British Journal of Surgery, 63:13-18.
• Lynch HT, Smyrk T and Lynch JF. (1996) Overview of natural history, pathology, molecular genetics and management of HNPCC (Lynch syndrome). International Journal of Cancer, 69:38-43.
• Lynch PM. (1999) Clinical challenges in management of familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer. Cancer, 86:1713-1719.
• Lynch T and Smyrk TC. (1999) Hereditary Colorectal Cancer. Seminars in Oncology, 5:478-484.
• Peckham CS and Dezateux C. (1998) Screening. The Royal Society of Medicine Press Limited, London.
• Petersen GM. (1996) Genetic counselling and predictive testing for colorectal cancer risk. International Journal of Cancer, 69:53-54.
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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References (continued)• Petersen GM, Brensinger JD, Johnson KA, et
al. (1999) Genetic testing and counselling for hereditary forms of colorectal cancer. Cancer, 86:1720-1730.
• Potter JD, Slattery ML, Bostick RM, et al. (1993) Colon Cancer: A review of the epidemiology. Epidemiologic Reviews, 15, No 2:499-545.
• Slattery ML and Kerber RA. (1994) Family history of Cancer and colon cancer risk: the Utah population database. Journal of the National Cancer Institute, 86:1618-1625.
• St.John DJB, McDermott FT, Hopper AL, et al. (1993) Cancer risk in relatives of patients with common colorectal cancer. Annals of internal medicine, 118:785-790.
• Toribara NW and Sleisenger MH. (1995) Screening for colo-rectal cancer. New England Journal of Medicine, 332:861-867.
• Vogelstein B, Fearon ER, Hamilton SR, et al. (1988) Genetic alterations during colo-rectal tumour development. New England Journal of Medicine, 319:525-532.
FACET - European Journal of Cancer CareMarch 2004
Genetics of colorectal cancer(continued)
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References (continued)• Westman J, Hampel H and Bradley T.
(2000) Efficacy of a touchscreen computer based family cancer history questionnaire and subsequent cancer risk assessment. Journal of Medical Genetics, 37:354-360.
• Wilmink ABM. (1997) Overview of the epidemiology of colorectal cancer. Diseases of the Colon and Rectum, 40, 4:483-493.
• Winawer SJ, Zauber AG, O'Brien MJ, et al. (1993) Prevention of colo-rectal cancer by colonoscopic polypectomy. New England Journal of Medicine, 329:1977-1981.