+
Screening for
Genetic Disease
Douglas Riegert-Johnson, MD
Assistant Professor of Medicine and
Medical Genetics
Mayo Clin...
+
Conflicts of Interest and
off Label Drug Use
None.
+
Objectives
What questions do I need to ask as a
primary care provider to screen for genetic
disease?
How do I refer a ...
+ What questions do I need to ask
to screen for genetic disease?
 Does anyone in your family have
cancer? Breast, ovarian...
+ What questions do I need to ask
to screen for genetic disease?
 Does anyone in your family have
cancer? Breast, ovarian...
+ Age of diagnosis and presence of an affected
family member changes the odds of a
hereditary cancer syndrome diagnosis
My...
+ Age of diagnosis and presence of an affected
family member changes the odds of a
hereditary cancer syndrome diagnosis
My...
+ Treatment is different for BRCA1/2
patients:
Bilateral mastectomy prolongs survival in patients with
BRCA1/2 mutations.
...
+
Hereditary cancer syndrome
patients are not rare!
Location by Zip Code
139 patients
(out of 280)
MCF 6.2014
+ Selected criteria for referral of the Breast
Cancer patient for genetic evaluation
Refer if patient has any of the follo...
+ Selected criteria for referral of the Breast
Cancer patient for genetic evaluation
 In unaffected patient if, family hi...
+
Simplified criteria for referring Colon
Cancer patients for genetic evaluation.
(Lynch syndrome)
NCCN 2.2014
 All patie...
+ Lynch Syndrome: Frequent colonoscopy is
protective for a colon cancer diagnosis (but does
not prevent all cases)
Järvine...
+ Lynch syndrome polyps are often flat and
difficult to detect. Indigo carmine chromoendoscopy 45 year old
female Lynch sy...
+ Overlooked polyps. Indigo carmine chromoendoscopy 45 year
old female Lynch syndrome patient (MLH1): Ascending colon poly...
+
2014 NCCN recommends all patients with colon
cancer be screened for Lynch syndrome by tumor
testing.
Protocol screen tes...
+
How do I refer a patient
for genetic evaluation?
+ www.nsgc.org
+
Genetic Counseling as a medical speciality
Under Graduate 4 years + Post Graduate 2 years
Specialty n
Internists 189,587
F...
+ NEXT GENeration Sequencing
Name for numerous
technologies used for
high through put
relatively low cost DNA
sequencing
...
+
BRCA1
BRCA2
ATM
BARD1
MSH2
MSH6 MLH1
Some of the genes included on
Next Generation panels for breast cancer
PALB2
NF1
CH...
+ Case presentation: Family with
breast cancer, but no BRCA1/2
mutation
30
62 40
22 2
Changes to medical
care:
Consider pr...
+
What genetic tests I can
perform as a non
geneticist?
+
Genetic tests commonly ordered.
 Would not recommend ordering any Next Gen
testing: Billing and interpretation too comp...
+ The new standard for genetic testing:
Randomized double blind controlled trials.
Discovery Medicine 2013.
51 patients wi...
+
Summary
 Cancer Family History should include cancer diagnosis and age
of diagnosis.
 Which patients should be referre...
+ The
End
+
Supplemental slides
Douglas Riegert-Johnson, MD
+
Revised Bethesda Criteria
 1.Colorectal cancer diagnosed under the age of 50 years of
age.
 2. Presence of synchronous...
+
Revised Bethesda Critieria
 * Hereditary Nonpolyposis Colorectal Cancer (HNPCC)-related tumors include
colorectal, endo...
32
Ver c 2014 clinical reviews amelia island (1)
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Transcript of "Ver c 2014 clinical reviews amelia island (1)"

  1. 1. + Screening for Genetic Disease Douglas Riegert-Johnson, MD Assistant Professor of Medicine and Medical Genetics Mayo Clinic Florida Amelia Island Mayo Clinic Review Course Douglas Riegert- Johnson, MD Riegertjohnson.douglas@mayo.edu Mayo Clinic Florida - Jacksonville Assistant Professor of Medicine and Medical Genetics
  2. 2. + Conflicts of Interest and off Label Drug Use None.
  3. 3. + Objectives What questions do I need to ask as a primary care provider to screen for genetic disease? How do I refer a patient for a genetic evaluation? What genetic tests can I order as a non geneticist?
  4. 4. + What questions do I need to ask to screen for genetic disease?  Does anyone in your family have cancer? Breast, ovarian, or colon cancer?  At what age were the cancers diagnosed? Breast cancer 80 Breast cancer 65
  5. 5. + What questions do I need to ask to screen for genetic disease?  Does anyone in your family have cancer? Breast, ovarian, or colon cancer?  At what age were the cancers diagnosed? Compliance with cancer family history in oncology practices 77% of medical records reviewed documented presence or absence of CFH in first-degree relatives. Of patients with increased risk for hereditary cancer, 52% of patients with Breast CA and 26% of those with Colorectal CA were referred for GC/GT. Quality of Cancer Family History and Referral for Genetic Counseling and Testing Among Oncology Practices: A Pilot Test of Quality Measures As Part of the American Society of Clinical Oncology Quality Oncology Practice Initiative J Clinical Oncology 2014 Breast cancer 80 41 Breast cancer 65 50
  6. 6. + Age of diagnosis and presence of an affected family member changes the odds of a hereditary cancer syndrome diagnosis Myraid Genetics BRCA mutation prevalence tables Personal history No family history of breast or ovarian cancer Family history of first degree relative with breast cancer dx < 50 yo Breast CA > 50yo 2.2% 8.0% Breast CA < 50 yo 4.7% 21.2% Male breast CA 6.9% 36.6% Ovarian CA 7.7% 27.4% * Not applicable to Ashkenzai Jewish populations.
  7. 7. + Age of diagnosis and presence of an affected family member changes the odds of a hereditary cancer syndrome diagnosis Myraid Genetics BRCA mutation prevalence tables Personal history No family history of breast or ovarian cancer Family history of first degree relative with breast cancer dx < 50 yo Breast CA > 50yo 2.2% 8.0% Breast CA < 50 yo 4.7% 21.2% Male breast CA 6.9% 36.6% Ovarian CA 7.7% 27.4% * Not applicable to Ashkenazi Jewish populations.
  8. 8. + Treatment is different for BRCA1/2 patients: Bilateral mastectomy prolongs survival in patients with BRCA1/2 mutations. Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations. BMJ 2013. 390 women with stage 1 or stage 2 breast cancer. All with a mutation in the BRCA ½ genes. 181 bilateral mastectomy 88% survival 209 unilateral mastectomy 66% survival * Survival at 20 years. Reduction in risk hazard ratio 0.52, 95% confidence interval 0.29 to 0.93; P=0.03.
  9. 9. + Hereditary cancer syndrome patients are not rare! Location by Zip Code 139 patients (out of 280) MCF 6.2014
  10. 10. + Selected criteria for referral of the Breast Cancer patient for genetic evaluation Refer if patient has any of the following  Early-age-onset breast cancer (less the 50 yo)  Breast cancer at any age if,  Triple negative (ER-, PR-, HER2-) breast cancer  Two breast primaries at any age  Personal history of breast cancer and family history of close blood relative with breast cancer dx <50yo  Ovarian/fallopian tube/primary peritoneal cancer  Male breast cancer NCCN 1.2014
  11. 11. + Selected criteria for referral of the Breast Cancer patient for genetic evaluation  In unaffected patient if, family history of  2 breast primaries in single individual close relative  2 individuals with breast primaries on the same side of family (maternal or paternal)  1 ovarian and breast primary from the same side of family (maternal or paternal)  First- or second-degree relative with breast cancer 45 y  1 family member on same side of family with a 1 of the following (especially if early onset): pancreatic cancer, aggressive prostate cancer (Gleason score 7) sarcoma, adrenocortical carcinoma, brain tumors, endometrial cancer, leukemia/lymphoma; features of Cowden syndrome.  From a population at increased risk (Ashkenazi Jewish) NCCN 1.2014
  12. 12. + Simplified criteria for referring Colon Cancer patients for genetic evaluation. (Lynch syndrome) NCCN 2.2014  All patients with colon cancer or endometrial cancer under the age of 50.  All patients with metachronous or synchronous colon cancer.  Any patient with colon cancer who has a family member with colon or endometrial cancer.*  Any patient with a specific colon cancer pathology  tumor-infiltrating lymphocytes,  Crohn's-like lymphocytic reaction,  mucinous/signet-ring differentiation,  or medullary growth pattern  Any patient with >10 cumulative colon adenomas * Revised Bethesda criteria in supplemental slides.
  13. 13. + Lynch Syndrome: Frequent colonoscopy is protective for a colon cancer diagnosis (but does not prevent all cases) Järvinen HJ, Gastroenterology 2000. 90 Lynch syndrome patients 44 Colonoscopy (every 3 years) 46 No colonoscopy 15 years Outcome Colonoscopy No colonoscopy Colon cancer dx 8 (18%) 19 (41%) Colon cancer deaths 0 4 Total deaths 4 (9%) 12(26%)
  14. 14. + Lynch syndrome polyps are often flat and difficult to detect. Indigo carmine chromoendoscopy 45 year old female Lynch syndrome patient (MLH1): Ascending colon polyp before injection with saline.
  15. 15. + Overlooked polyps. Indigo carmine chromoendoscopy 45 year old female Lynch syndrome patient (MLH1): Ascending colon polyp after injection with saline.
  16. 16. + 2014 NCCN recommends all patients with colon cancer be screened for Lynch syndrome by tumor testing. Protocol screen testing on tumors Immunohistochemistry (4 Lynch syndrome genes) Genetic testing on blood (germline) Colon cancer patients MCF 154 22 4 10 14 LS ptsIdentify family members
  17. 17. + How do I refer a patient for genetic evaluation?
  18. 18. + www.nsgc.org
  19. 19. +
  20. 20. Genetic Counseling as a medical speciality Under Graduate 4 years + Post Graduate 2 years Specialty n Internists 189,587 Family medicine specialists 114,000 GI 12,398 Genetic counselors 2,573 Medical geneticists 1,509 (all time)
  21. 21. + NEXT GENeration Sequencing Name for numerous technologies used for high through put relatively low cost DNA sequencing  Illumina – HiSeq  Ion torrent Conceivable to sequence 1 DNA base, but usually used for panels of genes Ion torrent
  22. 22. + BRCA1 BRCA2 ATM BARD1 MSH2 MSH6 MLH1 Some of the genes included on Next Generation panels for breast cancer PALB2 NF1 CHEK2 CDH1 TP53 RAD50 PMS2
  23. 23. + Case presentation: Family with breast cancer, but no BRCA1/2 mutation 30 62 40 22 2 Changes to medical care: Consider prophylactic mastectomy of females Pancreas cancer screening 22
  24. 24. + What genetic tests I can perform as a non geneticist?
  25. 25. + Genetic tests commonly ordered.  Would not recommend ordering any Next Gen testing: Billing and interpretation too complex.  Hemochromatosis HFE gene test  Indication: Elevated ferritin  Factor V Leiden in PTE  16% One copy: Recurrence risk VTE OR 1.56  ?1-2% Two copies: Recurrence risk VTE OR 2.56  At this time no convincing evidence testing changes should change duration of therapy.  No randomized controlled trials have shown any benefit to testing. Testing for Inherited Thrombophilia.Thrombosis and Hemostasis 2014.
  26. 26. + The new standard for genetic testing: Randomized double blind controlled trials. Discovery Medicine 2013. 51 patients with depression 26 Treatment guided by pharmacogenetics 25 Treatment as usual
  27. 27. + Summary  Cancer Family History should include cancer diagnosis and age of diagnosis.  Which patients should be referred for genetic counseling?  All breast, colon and endometrial cancer patients diagnosed under the age of 50.  All ovarian and male breast cancer patients regardless of age.  Newsflash: Screening of all colon cancers for Lynch syndrome is recommended and being implemented.  How to refer: Directory of genetic counselors at www.nsgc.org.  Genetic testing is maturing. The efficacy of genetic tests are being evaluated by DB RCTs. DRJ: I predict with further development of Next Generation sequencing DB RCTs will show utility in genetic testing in common diseases.
  28. 28. + The End
  29. 29. + Supplemental slides Douglas Riegert-Johnson, MD
  30. 30. + Revised Bethesda Criteria  1.Colorectal cancer diagnosed under the age of 50 years of age.  2. Presence of synchronous, metachron ous colorectal, or other HNPCC- associated tumors * , regardless of age.  3. Colorectal cancer with the MSI-H † histology € diagnosed in a patient who is less than 60 years of age.  4. Colorectal cancer diagnosed with one or more first-degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed under age 50 years.  5. Colorectal cancer diagnosed in two or more first or second degree relatives with HNPCC-related tumor, regardless of age. Used to identify colorectal cancers for Lynch syndrome tumor testing.
  31. 31. + Revised Bethesda Critieria  * Hereditary Nonpolyposis Colorectal Cancer (HNPCC)-related tumors include colorectal, endometrial, stomach, ovarian, pancreas, bladder, ureter and renal pelvis, biliary tract, brain (usually glioblastoma as seen in Turcot Syndrome), sebaceous gland adenomas and keratoacanthomas in Muir-Torre syndrome, and carcinoma of the small bowel.  † MSI-H = high microsatellite in stability in tumors refers to  changes in two or more of the five NCI-recommended panels of microsatellite markers. MSI-L = low microsatellite instability in tumors refers to changes in only one of the five NCI-recommended panels of microsatellite markers.  € Presence of tumor infiltrating lymphocytes, Crohn's-like lymphocytic reaction, mucinous/signet ring differentiation, or medullary growth pattern. There was no consensus on whether to include the age criteria  in point (3) above; participants voted to keep age 60 years in the guidelines. Continued
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