Curbside Consultation

Screening for Hereditary Cancer Syndromes

 


FREE PREVIEW. AAFP members and paid subscribers: Log in to get free access. All others: Purchase online access.


FREE PREVIEW. Purchase online access to read the full version of this article.

Am Fam Physician. 2015 Jan 15;91(2):125-131.

Case Scenario

My patient's wife died of pancreatic adenocarcinoma at 35 years of age. After her death, her doctor told my patient that their child might be at increased risk of developing pancreatic cancer. My patient asked if pancreatic screening and genetic testing were available for his eight-year-old daughter. He was referred to a genetic counselor specializing in cancer, who took a three-generation family history. It showed a strong family history of melanoma, suspicious for a hereditary cancer syndrome called familial atypical multiple mole melanoma (FAMMM) syndrome.

The genetic counselor recommended that my patient's brother-in-law or father-in-law (who had previously had melanoma), rather than his daughter, visit a geneticist to determine if he meets diagnostic criteria for FAMMM syndrome.

Several weeks later, the father-in-law and brother-in-law were found to meet the diagnostic criteria for FAMMM syndrome, but tested negative for a CDKN2A mutation.1 What recommendations should I make based on these results?

Commentary

Family physicians play a key role in identifying patients in need of increased cancer surveillance because of a personal or family history of cancer. How does one know if a patient warrants genetic testing for hereditary cancer predisposition? The first step is to take a family history. Consideration of increased screening recommendations, genetic counseling, or risk-reducing strategies may be warranted if there is a personal or family history of (1) cancer occurring at an unusually young age, (2) multiple primary tumors, (3) rare cancers such as male breast cancer, (4) several family members having the same or related forms of cancer, (5) criteria for genetic testing for a hereditary cancer syndrome, and (6) lack of environmental risk factors in a cancer with environmental triggers.2 The ultimate goal is to determine whether a patient has a cancer risk that necessitates changes in lifestyle and medical management.

Genetic testing is not always informative, but the family history can provide the information needed to decide if a patient needs increased screening. The American College of Medical Genetics and Genomics and the American Academy of Pediatrics recommend performing presymptomatic genetic testing in minors at risk of childhood-onset conditions and deferring genetic testing for adult-onset conditions, unless an intervention initiated in childhood may reduce morbidity or mortality.3,4

When an adult patient has an unexplained personal or family history of cancer, the best outcome is to identify a cancer-causing mutation. When a mutation is found, testing asymptomatic family members can identify “true positives” who are in need of increased screening and prevention strategies from “true negatives” who do not need increased screening. There are many reasons a patient's genetic test results can be negative, including a mutation in an as-yet-undiscovered gene, a mutation that current technology cannot detect, or a true sporadic cancer. However, when a mutation is not found, it is important to take a second look at the family history to determine whether the patient or family members meet increased screening guidelines based on family history alone.

FAMMM syndrome is an autosomal dominant disorder with increased risks of developing melanoma and pancreatic cancer. Patients who have FAMMM syndrome and a CDKN2A mutation have a 60% to 90% chance of developing melanoma by 80 years of age and a 17% chance of developing pancreatic cancer by 75 years of age.5,6 The cancer risks for patients who have FAMMM syndrome without a CDKN2A mutation are variable.7 Because the family in this case scenario met the clinical diagnostic criteria for FAMMM syndrome, all family members, first-degree relatives, and some second-degree relatives should follow FAMMM syndrome screening guidelines and should consider enrolling in a clinical research screening program.8

FAMMM syndrome screening guidelines begin at 10 years of age with a baseline total body skin examination. There is no established screening guideline for individuals at increased risk of developing pancreatic cancer. However, International Cancer of the Pancreas Screening Consortium recommends consideration of pancreatic screening in CDKN2A carriers with one first-degree relative diagnosed with pancreatic cancer by endoscopic ultrasonography or by magnetic resonance imaging/magnetic resonance cholangiopancreatography. Consensus was not reached on the age to initiate screening.9 Currently, the effectiveness of screening for pancreatic cancer has not been established. It is recommended that screening be performed as part of a research protocol and/or at a center with demonstrated expertise in pancreatic diseases and a comprehensive genetic counseling program.9

Identifying a patient who is at increased risk of developing cancer or who has a hereditary cancer syndrome helps physicians make changes to a patient's medical management that address these risks.10 Diagnosis of a hereditary cancer syndrome affects not only the patient but also the patient's family members. Policy statements, as well as other research, stipulate that physicians have a duty to inform patients about a family's cancer risk.1113

This case demonstrates that partnering with a genetic counselor can save time and improve care by identifying patients or family members who would benefit from genetic screening.14  Table 1 lists resources on genetic counseling and inherited diseases.

View/Print Table

Table 1.

Resources on Inherited Diseases and Genetic Counseling

ResourceDescription

Cancer.Net (http://www.cancer.net/navigating-cancer-care/cancer-basics/genetics)

A collection of patient-oriented information on cancer care from the American Society of Clinical Oncology and the Conquer Cancer Foundation

GeneReviews (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

Covers the diagnosis, management, and counseling of heritable diseases in a series of peer-reviewed chapters

InformedDNA (http://informeddna.com/)

For physicians in rural areas; offers individualized genetic counseling by telephone

National Society of Genetic Counselors (http://www.nsgc.org/)

Includes tools for finding local genetic counselors and recommendations for including them in practice

Table 1.

Resources on Inherited Diseases and Genetic Counseling

ResourceDescription

Cancer.Net (http://www.cancer.net/navigating-cancer-care/cancer-basics/genetics)

A collection of patient-oriented information on cancer care from the American Society of Clinical Oncology and the Conquer Cancer Foundation

GeneReviews (http://www.ncbi.nlm.nih.gov/books/NBK1116/)

Covers the diagnosis, management, and counseling of heritable diseases in a series of peer-reviewed chapters

InformedDNA (http://informeddna.com/)

For physicians in rural areas; offers individualized genetic counseling by telephone

National Society of Genetic Counselors (http://www.nsgc.org/)

Includes tools for finding local genetic counselors and recommendations for including them in practice

The authors thank Louise Amlie-Wolf, MS, CGC, and Daniel Morales for their assistance with the manuscript.

Address correspondence to Ku-Lang Chang, MD, FAAFP, at changk@shands.ufl.edu. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

REFERENCES

show all references

1. Diagnosis and treatment of early melanoma. NIH Consensus Development Conference. January 27–29, 1992. Consens Statement. 1992;10(1):1–25....

2. Bennett RL. The Practical Guide to the Genetic Family History. 2nd ed. Hoboken, N.J.: Wiley-Blackwell; 2010.

3. Committee on Bioethics, Committee on Genetics, and the American College of Medical Genetics and Genomics Social, Ethical, and Legal Issues Committee. Ethical and policy issues in genetic testing and screening of children: policy statement. Pediatrics. 2013;131(3):620–622.

4. Ross LF, et al. Technical report: ethical and policy issues in genetic testing and screening of children [published correction appears in Genet Med. 2013;15(4):321]. Genet Med. 2013;15(3):234–245.

5. Parker JF, et al. Pancreatic carcinoma surveillance in patients with familial melanoma. Arch Dermatol. 2003;139(8):1019–1025.

6. Vasen HF, et al. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer. 2000;87(6):809–811.

7. Eckerle Mize D, Bishop M, Resse E, Sluzevich J. Familial atypical multiple mole melanoma syndrome. In: Riegert-Johnson DL, Boardman LA, Hefferon T, Roberts M, eds. Cancer Syndromes [Internet]. Bethesda, Md.: National Center for Biotechnology Information; 2009.

8. Czajkowski R, et al. FAMMM syndrome: pathogenesis and management. Dermatol Surg. 2004;30(2 pt 2):291–296.

9. Canto MI, et al. International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer [published correction appears in Gut. 2014;63(1):178]. Gut. 2013;62(3):339–347.

10. Riley BD, et al. Essential elements of genetic cancer risk assessment, counseling, and testing: updated recommendations of the National Society of Genetic Counselors. J Genet Couns. 2012;21(2):151–161.

11. American Society of Clinical Oncology policy statement update: genetic testing for cancer susceptibility. J Clin Oncol. 2003;21(12):2397–2406.

12. Storm C, Agarwal R, Offit K. Ethical and legal implications of cancer genetic testing: do physicians have a duty to warn patients' relatives about possible genetic risks? J Oncol Pract. 2008;4(5):229–230.

13. American Medical Association. Opinion 2.131—Disclosure of familial risk in genetic testing. http://www.ama-assn.org/ama/pub/physician-resources/medical-ethics/code-medical-ethics/opinion2131.page. Accessed September 9, 2014.

14. Hampel H, et al. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment [published online ahead of print November 13, 2014]. Genet Med. https://www.acmg.net/docs/ACMG_Practice_Guideline_Referral_Indi-cations_for_cancer_predisposition.pdf. Accessed December 22, 2014.

Case scenarios are written to express typical situations that family physicians may encounter; authors remain anonymous. Send scenarios to afpjournal@aafp.org. Materials are edited to retain confidentiality.

This series is coordinated by Caroline Wellbery, MD, Associate Deputy Editor.

A collection of Curbside Consultation published in AFP is available at http://www.aafp.org/afp/curbside.

Please send scenarios to Caroline Wellbery, MD, at afpjournal@aafp.org. Materials are edited to retain confidentiality.



 

Copyright © 2015 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions


More in AFP


Editor's Collections


Related Content


More in Pubmed

MOST RECENT ISSUE


Oct 1, 2016

Access the latest issue of American Family Physician

Read the Issue


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article