Download Mar 2004 - Genetics of colorectal cancer I. Rafi

FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
Rafi, I.1
Ascertainment
Slide One
• Good family history
• Use of computers
• Questionnaire
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Two
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
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Epidemiology
Slide Three
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
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Four
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 premalignant adenomatous polyps.
• Pre-existing adenomas
• Several genetic abnormalities
and genes involved
• Environment-genetic interplay
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Screening
• Do relatives of an affected
Slide Five
individual with colorectal cancer
have a greater lifetime risk
compared to normal
population?
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Screening/outcomes
Slide Six
• Mortality
• Type of screening
• Evidence base
• Targeted v general population
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Genetic Families at
Risk
Slide Seven
• Familial Adenomatous Polyposis
(FAP)
• Hereditary Non-Polyposis Coli
(HNPCC)
• Familial Colorectal Cancer (FCC)
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Eight
Familial
Adenomatous
Poylposis
• Germ-line mutations in the APC
gene
• Undifferentiated growth of
adenomas
• Extra-colonic manifestations
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
HNPCC
• Mutation in genes essential for
Slide Nine
DNA mismatch repair
• Right sided colonic tumours
• Extra colonic cancers such as
endometrial, ovarian, bladder
and renal tumours
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Familial
Families have an increased lifetime
risk of developing colorectal cancer
Slide Ten
where there is a first-degree relative
with colorectal cancer.
Risk stratification based on:
• Number of first degree
relatives affected
• Early age of cancers
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Genetic
epidemiology
Slide Eleven
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
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Genetic Studies
Slide Twelve
• Burt (1996)
• St John et al (1993)
• Utah population data (1994)
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Thirteen
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
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Fourteen
Screening methods
(1)
• FAP
• Sigmoidoscopy (starting in
adolescence)
• Gastro-duodenoscopy
• Gene testing for the APC gene
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Fifteen
Screening methods
(2)
• HNPCC
• Colonoscopy
• ? Pelvic Ultrasound
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Screening by genetic
testing
Slide Sixteen
• 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
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Conclusion
Slide Seventeen
• Evidence that screening affects
mortality is sparse
• Further research
• Need for clear referral criteria
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Eighteen
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
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4:426-445.
*Click on “View”; “Notes Page” for explanatory notes
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Nineteen
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 gastrointestinal tract. British Journal of Surgery, 63:19-22.
*Click on “View”; “Notes Page” for explanatory notes
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Twenty
References (continued)
•
Lovett E. (1976b) Family studies in cancer of the
colon and rectum. British Journal of Surgery, 63:1318.
•
Lynch HT, Smyrk T and Lynch JF. (1996) Overview of
natural history, pathology, molecular genetics and
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International Journal of Cancer, 69:38-43.
•
Lynch PM. (1999) Clinical challenges in management
of familial adenomatous polyposis and hereditary
nonpolyposis colorectal cancer. Cancer, 86:17131719.
•
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.
*Click on “View”; “Notes Page” for explanatory notes
slides available at: www.blackwellpublishing.com/journals/ecc
FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Twenty One
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
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*Click on “View”; “Notes Page” for explanatory notes
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FACET - European Journal of Cancer Care
March 2004
Genetics of colorectal cancer
(continued)
Slide Twenty Two
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.
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