Cancer genetics in primary care

Cancer genetics in primary care Prof Shirley Hodgson Professor of Medical Genetics, St Georges Hospital, London Dr Jon Emery Cancer Research UK Clinician Scientist and GP, Dept Public Health & Primary Care, University of Cambridge Familial Clustering of Cancer • Epidemiological studies show an increased relative risk of cancer in individuals with a family history of cancer • This is probably due to a mixture of rare highly penetrant genes, commoner lower penetrance genes and environmental effects Hereditary Non-Polyposis Colon Cancer • 80% lifetime risk of colorectal cancer (males) • 60% lifetime risk of endometrial cancer • 10% risk of ovarian cancer • Surveillance 1-2 yearly colonoscopies from 25y • Consider endometrial screening by ultrasound and endometrial pipelle biopsy • Consider ovarian screening by transvaginal ultrasound Moderate Colorectal Cancer Risk • Two first-degree relatives affected (0.4% population) • One first-degree relative diagnosed <45y (0.2% population) • Suggest colonoscopy at 35y (2% risk of polyp) and 55y (17-21% risk of polyp) BRCA1 and BRCA2 • High (60-80%) lifetime risk of breast cancer, both genes. • Increased ovarian cancer risk (BRCA1>BRCA2) • Surveillance for both indicated; mammography, MRI, TV ultrasound • Consider prophylactic surgery Breast cancer criteria • • • • High risk Breast and breast/ovarian families with 4 or more relatives, on the same side of the family, affected at any age. Breast cancer only families with 2 affected relatives, average age of diagnosis <40. Breast/ovarian cancer families with 3 affected relatives, on the same side of the family, average age of diagnosis of breast cancer <60. Families with one member with both breast and ovarian cancer. Moderate risk Three first or second degree relatives, on the same side of the family, with breast or ovarian cancer. Two first or second degree female relatives, on the same side of the family, with breast cancer diagnosed <60, or ovarian cancer at any age. One first degree female relative with breast cancer diagnosed <40. One second degree female relative on the paternal side of the family diagnosed <40. One first degree male relative with breast cancer diagnosed at any age. One first degree female relative with bilateral breast cancer (first diagnosis <60). • • • • • • • • Mrs T is 39 and asks for a mammogram because of her family history of breast cancer. Her mother was diagnosed with the disease at 62 as was her maternal grandmother at 58. She has a paternal aunt who has recently been diagnosed at 54 and a maternal aunt with bowel cancer at 56.There is no other family history of note. Is this a significant family history? Will she benefit from having regular mammograms at this age? Scenario • Small increased risk due to age of onset of breast cancer in relatives • Paternal aunt considered separately • Early mammography not currently recommended Cancer genetics and primary care • 40-50 patients per GP have family history of breast or bowel cancer • 1-2 patients per month discuss family history of cancer with GP • Media attention about cancer and genetic testing • Referrals to cancer genetics clinic at Addenbrookes rose from 400 to 800 in year to mid 1999 Role of GP in cancer genetics • Family history assessment – type of cancer – relationship to patient – age at diagnosis • Stratify risk and manage appropriately • Requires integration of new skills with existing ones Supporting cancer risk assessment: referral guidelines High risk Breast and breast/ovarian families with 4 or more relatives, on the same side of the family, affected at any age. Breast cancer only families with 2 affected relatives, average age of diagnosis <40. Breast/ovarian cancer families with 3 affected relatives, on the same side of the family, average age of diagnosis of breast cancer <60. Families with one member with both breast and ovarian cancer. Moderate risk Three first or second degree relatives, on the same side of the family, with breast or ovarian cancer. Two first or second degree female relatives, on the same side of the family, with breast cancer diagnosed <60, or ovarian cancer at any age. One first degree female relative with breast cancer diagnosed <40. One second degree female relative on the paternal side of the family diagnosed <40. One first degree male relative with breast cancer diagnosed at any age. One first degree female relative with bilateral breast cancer (first diagnosis <60). NICE guidelines coming soon… Guideline chaos in primary care! Education and guidelines • Watson et al: BrJGP 2001; 51:817-821. J Med Genet 2002;39: 779-81 • Cluster RCT referral guidelines +/- educational visit vs control • Trend toward improved referrals The GRAIDS Trial Lead clinician Genetic Skills Genetic knowledge Education & training Generic consulting skills GRAIDS software via NHSnet High quality cancer genetic advice in primary care GRAIDS Demonstration Future possibilities Regional Genetics Clinic Central server Sophistication of GRAIDS NHSnet Cancer Units Primary care Consumer Internet