Lynch Syndrome (HNPCC), MAP

Etiology and Clinical Features of Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) and MYH-associated polyposis (MAP)

Lynch syndrome, also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC), is the most common of the hereditary colon cancer syndromes and is believed to account for 3% to 5% of all colorectal cancers.40 Henry T. Lynch, M.D., described the features of this syndrome in 1966 while conducting familial colorectal cancer studies.41 A variety of names followed, but the term Lynch syndrome was first used in 1984 to help clarify the disease and to honor Dr Lynch’s work.41

It is now known that Lynch syndrome results from an inherited mutation in one of the mismatch repair (MMR) genes. Normally, MMR genes produce proteins that identify and correct base-pairing mismatches that can occur during DNA replication. Consequently, a mutation that inactivates an MMR gene leads to accumulation of other mutations which significantly increases the likelihood of developing cancer. Mutations that disrupt the function of MMR genes (mutations in MLH1MSH2, MSH6, EPCAM and PMS2) have been linked to Lynch syndrome.42,43

It has been known that germline mutations in MLH1, MSH2 and MSH6 account for the majority of detected mutations in families with Lynch syndrome.44  More recently it has been discovered that PMS2 and EPCAM also play an important role in Lynch syndrome.

As one of the four primary mismatch repair genes associated with Lynch syndrome, the functional importance of PMS2 has been clear, but its total contribution to Lynch syndrome was historically considered to be quite low.  More recent studies suggest that the prevalence of PMS2 mutations is comparable to MSH6, with as much as 15% of all Lynch syndrome attributable to PMS2.

The EPCAM gene is a recently discovered contributor to Lynch syndrome, accounting for an estimated 1-3% of all detectable Lynch syndrome mutations.  Studies indicate that large deletions in the end of this gene, which is located directly “upstream” of MSH2, can lead to a loss of MSH2 expression and result in Lynch syndrome.

MYH-associated polyposis (MAP) is caused by mutations in the mutY homolog (MYH) gene.  MAP is inherited in an autosomal recessive manner.  Individuals with MAP have mutations in both of their MYH genes (one from each parent, often referred to as “biallelic MYH mutations”).  Patients often have no family history of colon cancer or polyps in parents (although siblings may be affected).83  The MYH gene is an important part of the base excision repair (BER) pathway, which allows for repair of DNA mutations caused by oxidative damage to cells. MAP is believed to account for approximately 1% of all colorectal cancers. MAP can cause patients to develop colorectal cancer even in the absence of colon polyposis.280

Individuals with Lynch syndrome have an increased risk of colorectal cancer – at least 25% by age 50 and up to 82% by age 70 and a risk of up to 90% to develop some type of cancer.47,48 The risk for certain other cancers, primarily endometrial (up to 71%), ovarian (up to 12%) and gastric (up to 13%) is also increased in Lynch syndrome.  Mutation carriers previously diagnosed with cancer also have a significantly increased risk of developing a second primary (new) cancer of up to 50% within 15 years of the first diagnosis.49 Patients who have MYH¬-associated polyposis (MAP) have up to an 80% risk of developing colorectal cancer.281

Genetic testing identifies patients who have germline mutations in the genes responsible for Lynch syndrome and MAP.  This information is useful when developing risk-reducing strategies for these patients.

 

The results of the COLARIS® test enable the development of a patient-specific medical management roadmap to significantly reduce the risk of cancer.  COLARIS will help you to:

  • Target increased surveillance and other interventions specifically to individuals with a Lynch syndrome or MYH-associated polyposis mutation(s)—maximizing patient care and increasing clinical efficiency
  • Improve patient compliance with tailored screening recommendations and preventive measures
  • Significantly improve outcomes and reduce medical costs through prevention, earlier diagnosis and treatment of cancer, should it develop
  • Counsel patients and family members on the underlying cause of cancer in their family
  • Avoid unnecessary interventions for family members who do not test positive for the mutation(s) known to be in the family
Medical Management Strategies that May Reduce the Risk of Cancer

Once a diagnosis of Lynch syndrome is confirmed, the following medical management options may help reduce cancer risk or detect cancer at an earlier, more treatable stage or even prevent it.*†

Lynch syndrome Management

Colon Cancer

Surveillance for Colorectal Cancer

  • Colonoscopy every 1-2 years beginning between age 20 and 25, OR 10 years before the earliest age of a patient’s family member diagnosed with colorectal cancer – whichever comes first50
  • Consider annual colonoscopy after age 4051,52,53
  • For MSH6 mutation carriers consider initiating colonscopy screending at age 30 – 35 or 10 years before the earliest age of a patient’s family member diagnosed with colorectal cancer.  This is due to the later average age of onset in MSH6 mutation carriers50

Surgical Management of Colorectal Cancer

  • If colon cancer is diagnosed (or more than one advanced adenoma is found) in a patient with Lynch syndrome, total colectomy with ileorectal anastomosis OR hemicolectomy is an option50,54
  • In patients unwilling or unable to undergo periodic colonscopy screening, prophylactic total colectomy with ileorectal anastomosis may be an option based on carrier status alone50,51,54

Endometrial and Ovarian Cancer

Surveillance for Endometrial and Ovarian Cancer

  • Consideration of referral to a gynecologic oncologist to discuss screening options with can include gynecologic exam, transvaginal ultrasound, endometrial aspiration and CA-125 every year, beginning between age 25 and 3550,51,52,55,56

Surgical Management ofEndometrial and Ovarian Cancer

  • Prophylactic total abdominal hysterectomy and bilateral salpingo-oophorectomy is a risk reducing option for women who have completed childbearing
    • May also be considered at time of colon surgery if postmenopausal or childbearing is complete50

Surveillance for Other Lynch Syndrome-Related Cancers

  • For gastric and duodenal cancer: Consider upper GI endoscopy (wide side viewing scope) at age 25 – 30 years and repeat every 1 to 3 years depending on findings
  • For urothelial cancer: Consider urinalysis on an annual basis
  • For CNS cancer: Physical examination on an annual basis

MYH-Associated Polyposis (MAP) Management:

  • For patients who have MAP, medical society management recommendations include colonoscopies every 1-2 years starting at age 25-30, upper endoscopies every 3-5 years starting at age 30-35, and surgical considerations. The most appropriate medical management will vary based upon your patient’s clinical presentation.282 
  • For MYH mutation carriers (1 mutation), medical management should be determined by clinical findings and personal and family history of colorectal polyps and/or cancer. Current data are limited but suggest that any increase in risk, if present, is likely to be small.283

The following table is based on regularly updated data representing the observations of deleterious mutations in the MLH1 and MSH2 genes by Myriad Genetic Laboratories, Inc. through our clinical testing service. Prevalence data for MSH6 mutations, which account for 10% to 15% of detectable mutations in HNPCC, are not yet available. These data were obtained from a routine laboratory requisition form and have not been independently verified. Data obtained through testing performed under specific research protocols and data for whom relevant information was not provided are excluded from this tabulation. Personal History categories will be added as data becomes available. Please contact clinresearch@myriad.com or call 800-469-7423 with any questions/comments.

MLH1 and MSH2 Prevalence Table

The Prevalence of Deleterious Mutations in MLH1 or MSH2 (N=3410)

Family History (Includes at least one first or second degree relative)

Personal History No Affected Relatives ≥ 1 Relative Affected
Colorectal Cancer < 50 7.2% 27.5%
Colorectal Cancer ≥ 50 4.4% 14.1%
Endometrial Cancer < 50 7.0%* 29.9%
Other Lynch Syndrome Cancer 3.6%** 14.3%
>1 Lynch Syndrome Cancer 8.8% 45.8%

*Estimate calculated according to PREMM12 model; Myriad’s N < 25
**Myriad’s N < 50

Listed below are examples of the possible test results for COLARIS® genetic testing.

COLARIS Positive Sample Report
Example of a patient that is positive for a MSH2 mutation
COLARIS Negative Sample Report
Example of a patient with no mutation detected
COLARIS Variant of Uncertain Significance (VUS) Sample Report
Example of a patient with no clinically significant mutation identified

Guidelines for Letters of Medical Necessity (LMNs)

A healthcare provider may include a LMN with a pre-authorization request, claim submission, or appeal to facilitate the insurance review process for the benefit of the patient. Our experience with insurance companies is such that we encourage healthcare providers to cover as many of the following points as possible that are applicable to the patient:

  • Explanation that the requested genetic test has been ordered by a physician
  • Explanation of the medical necessity for the test requested
  • If family history is cited, give as much family history as possible, including specifics about relationship to patient, cancer site, age of cancer diagnosis (alternatively, a detailed three-generation pedigree that contains this information could be attached and referred to in the body of the letter)
  • Patient’s diagnosis and prognosis, including age of onset and specific location of cancer
  • Explanation that the genetic test is recognized as appropriate for inclusion in this patient’s treatment regimen
  • Treatment plan, including specific statements about anticipated impact of the genetic test on the medical management of patient.

We remind you to read through the entire letter to make sure it makes sense for each patient. Please call 800-469-7423 if Myriad Customer Service may provide further assistance or answer questions.

Tips for Saving and Modifiying Sample LMNs:

This is a Microsoft Word document that is saved as “read-only” to preserve the original wording. To customize, simply use the “save as” command from the “File” menu, which will prompt you to rename the document to something besides the original name. Your newly named document is no longer “read-only” and can be modified as you wish.

COLARIS AP® Sample Family Letters

The following letters are examples of what your patients can write and send to their relatives with a copy of their COLARIS AP® test results.

How is the COLARIS test performed?

There are now two ways to obtain a sample from the patient for analysis. A small amount of blood can be drawn, or an oral sample can be taken using a buccal rinse. A sample is sent to Myriad Genetic Laboratories, Inc for DNA sequencing analysis of MLH1, MSH2, MSH6, PMS2 and MYH. COLARIS can also detect large rearrangements in MLH1, MSH2, MSH6, EPCAM, PMS2 and MYH that will not be identified by gene sequencing.

How long does it take for COLARIS test results?

Results take up to 21 days after insurance approval and are sent to the ordering healthcare provider or to a designated “mail to” provider identified on the test request form.

Will a patient's health insurance cover the test?

Most health insurance plans pay for COLARIS. Patients typically pay co-insurance of less than 10% of the test price. Myriad will notify you before processing your test if you total financial responsibility exceeds $375 (or $15 per month when utilizing our interest-free 25-month payment plan) for any reason, including co-insurance, deductible, or non-covered services. Call Myriad at 800-469-7423 for more details.

Can a health insurance provider discriminate against a patient based on COLARIS results?

Federal and state governments recognize the value of genetic information to patients and doctors and have put specific legal protections in place. The Genetic Information Nondiscrimination Act or GINA adds additional protection to existing legal protections that are in place at both the federal and state levels. GINA is a federal law that protects Americans from being treated unfairly based on differences in their DNA. GINA prevents discrimination from health insurers and employers. Health insurers are prohibited from requesting or requiring an individual or family member to undergo a genetic test or requesting, requiring, or purchasing genetic information, nor can they use an individual’s genetic information in setting eligibility, premium or contribution amounts by group and individual health insurers. GINA also protects individuals from employers requesting, requiring, or purchasing genetic information about an individual employee or family member. In addition, the employer is prohibited from using an individual’s genetic information in employment decisions such as hiring, firing, job assignments and promotions.

The Health Insurance Portability & Accountability Act (HIPAA) recognizes genetic information as Protected Health Information (PHI) and specifies protecting its confidentiality. HIPAA further states that “genetic information shall not be treated as a pre-existing condition in the absence of a diagnosis of the condition related to such information,” e.g., a diagnosis of hereditary cancer. The Americans with Disabilities Act (ADA) provides additional protections regarding the use of genetic information by employers.

Almost all states have additional laws that protect people from various forms of health insurance and employment discrimination based on genetic information. For more information about how these laws apply to you, go to the National Human Genome Research Institute.

If a patient has already been diagnosed with cancer, what does a positive COLARIS result indicate?

Individuals with Lynch syndrome gene mutations are at greater risk for developing a new cancer, in either the colon, endometrium or other areas. Knowing a patient’s genetic status can help reduce this risk or detect another potential cancer at an early, more treatable stage. Importantly, a patient’s test results also have significant meaning for the health of his or her family members.

Will this change impact insurance coverage for COLARIS?

Coverage for the COLARISPlus test with MYH enhancements will be equivalent to the current coverage for COLARIS. PMS2 testing will be reported and billed independently. While each case is unique, PMS2 coverage is supported by most payors. If PMS2 is not a covered test, a Patient Services Coordinator will contact your patient to determine if they would still like to proceed with PMS2testing utilizing one of our payment options. Processing of the other COLARIS gene testing will not be delayed while we contact your patient.

Will the enhanced COLARIS be available through Myriad's Patient Assistance Program?

Yes, uninsured patient meeting the clinical and financial criteria will be able to get testing at no charge. The criteria are listed here.

When will the new COLARIS kits and Test Request Forms (TRFs) be distributed?

Replacements test kits shipped after mid-May 2011 will have a new kit design and will contain the new TRFs. Additionally, Myriad Sales Representatives will have supplies of new COLARIS kits and TRFs to replace existing kits in your office.

Can I order the PMS2 test if I don't have the new TRF?

Yes. Pre-2011 TRF versions specify only MLH1, MSH2 and MSH6 gene analysis for COLARIS. Only TRFs with a version date of 03-11 or newer include PMS2 as a part of COLARIS. Accordingly, if you are using an old TRF and also desire to order PMS2 testing, check “Gene Specific Testing” and clearly specify the gene testing you’re adding to the order – in this case, “PMS2 analysis.”

Are gene-specific and single-site tests still available on the new TRF?

Yes. These tests can be ordered by completing the “Single Site Testing” or “Gene Specific Testing” section beneath the comprehensive test on the new TRF. Gene-specific testing may include combinations of genes ordered concurrently or as reflex tests. Detailed explanations of all test offering appear on the back of the test request form.

How do I order only the COLARIS enhancements for a patient who tested negative prior to May 17, 2011?

For a limited time Myriad is offering a COLARIS Update test that include sequencing and large rearrangement analysis of PMS2 and large rearrangement analysis of EPCAM and MSH6 for patients who tested negative prior to May 17, 2011. To order, check the COLARIS Update box on the COLARIS TRF with a version date of 03-11 or newer.

How will the new enhancements be reported?

MSH6 and EPCAM large rearrangements will be included with the COLARIS testing results. PMS2 analysis will be reported on a separate page in the same packet if run concurrently. If PMS2 is run sequentially it will be reported separately.

How will Medicare submissions be handled? Will it affect my reporting time?

Medicare and a small number of payors PMS2 testing to be run only following a negative result for MLH1, MSH2 and MSH6. For these cases, we will run PMS2 as reflex tests, with results reported separately in approximately 28 days after receipt.

How do I order COLARIS AP® testing?

COLARIS and COLARIS AP testing are no longer offered on the same TRF. If you do not have a COLARIS AP test kit, you can write in COLARIS AP in the “other” section on the COLARIS TRF. COLARIS AP test kits may also be obtained from your Myriad Sales Representative, online or by calling 800-469-7423.

What are COLARIS[PLUS] and COLARIS AP [PLUS]

COLARISPLUS and COLARIS APPLUS are Comprehensive COLARIS and Comprehensive COLARIS AP plus MYH full sequencing and large rearrangements.

Will the price be increasing with the MYH enhancement?

No. There will be no price increase with the MYH enhancement.

Will this change impact insurance coverage for COLARIS and COLARIS AP?

No. Coverage for the COLARISPLUS and COLARIS APPLUS tests with MYH enhancements will be equivalent to the current coverage.

How will Medicare submissions be handled?

The process for Medicare submissions will not change for COLARISPLUS and COLARIS APPLUS. MYH will be run concurrently with MLH1, MSH2, MSH6, and EPCAM. PMS2 will continue to be run as a reflex test.

When will the MYH enhancement take effect?

All Comprehensive COLARIS and Comprehensive COLARIS AP orders received on or after February 6, 2013 will automatically include MYH analysis.

Will MYH analysis be run twice if I order both COLARIS[PLUS] and COLARIS AP[PLUS] testing?

No. MYH analysis will only be processed and reported once if both COLARISPLUS and COLARIS APPLUS testing are ordered, or if MYHgene analysis has been completed in the past.

How do I manage MYH-Associated Polyposis (MAP) syndrome patients?

Medical society management recommendations for MAP include colonoscopies every 1-2 years starting at age 25-30, upper endoscopies every 3-5 years starting at age 30-35, and surgical considerations. The most appropriate medical management will vary based upon your patient’s clinical presentation. View our medical management references.

How do I manage patients who received a single MYH mutation result?

Medical management should be determined by clinicalfindings and personal and family history of colorectal polyps and/or cancer. Current data are limited but suggest that any increase in risk, if present, is likely to be small (N Engl J Med 2003;348:791-799; Lancet 2003;362:39-41; J Natl Cancer Inst 2004;96:1631-1634).

Do I need to order MYH gene analysis on my patient if they had prior COLARIS or COLARIS AP testing and did not receive MYH full-sequencing and large rearrangement gene analysis?

MYH analysis should be ordered for previously tested patients at the discretion of the healthcare provider. To order MYH analysis for previously tested patients, write in “MYH analysis” in the “other” section of the COLARIS or COLARIS AP Test Request Form (TRF). MYH analysis test orders for previously tested patients will follow our normal customer service process. The cost of MYHanalysis when ordered independently is $1,340.

Will the MYH enhancements increase turn around time?

No. COLARISPLUS and COLARIS APPLUS will still be reported up to 21 days after insurance approval.

When will the new Test Request Forms (TRFs) with the COLARIS[PLUS] and COLARIS AP test offerings be distributed?

Test kits shipped after late February 2013 will contain new TRFs. However, Myriad will automatically include MYH analysis on all Comprehensive COLARIS or Comprehensive COLARIS AP orders processed on or after February 6, 2013.

How will the new enhancements be reported for COLARIS[PLUS] and COLARIS AP?

Similar to PMS2 analysis, MYH analysis will be reported on a separate page, in the same packet as COLARIS results report. MYHwill be reported on the same report for COLARIS APPLUS results.

Polyposis Syndromes (FAP, AFAP, MAP)

Etiology and Clinical Features of Adenomatous Polyposis Syndromes

The most common adenomatous polyposis conditions are thought to account for approximately 2% of all colon cancer.81,82 They can be categorized into three conditions: familial adenomatous polyposis, attentuated familial adenomatous polyposis and MYH-associated polyposis.

Classic familial adenomatous polyposis (FAP) and attentuated familial adenomatous polyposis (AFAP) are due to mutations in the adenomatous polyposis coli (APC) gene. The APC gene is a tumor suppressor gene which regulates cellular growth and proliferation. Both FAP and AFAP are inherited in an autosomal dominant manner. MYH-associated polyposis (MAP) is caused by mutations in the mutY homolog (MYH) gene. MAP is inherited in an autosomal recessive manner. Individuals with MAP have mutations in both of their MYH genes (one from each parent, often referred to as “biallelic MYH mutations”). Patients often have no family history of colon cancer or polyps in parents (although siblings may be affected).83 The MYH gene is an important part of the base excision repair (BER) pathway, which allows for repair of DNA mutations caused by oxidative damage to cells. MAP is believed to account for approximately 1% of all colorectal cancers. MAP can cause patients to develop colorectal cancer even in the absence of colon polyposis.280

When assessing hereditary cancer risk, a patient’s personal and family history is collected to investigate the risk for a polyposis syndrome. Once a patient is identified as being at increased risk for one of these syndromes, genetic test results provide the most accurate means of cancer risk assessment for a patient. It is important to note that approximately 20% to 30% of FAP cases are caused by new mutations, meaning that an APC germline mutations may be present in an individual even if it is absent in both parents.84 Also, due to the autosomal recessive inheritance pattern of MAP, many affected patients have no relatives with colorectal polyps or cancer.83 Genetic testing is the only way to identify truly at-risk family members.

Patients testing positive for an APC gene mutation have up to a 100% lifetime risk of developing colorectal cancer and a slightly increased risk for other cancers.85 Specific risk percentages for patients who have an APC mutation appear below. Patients who have MYH­-associated polyposis (MAP) have up to an 80% risk of developing colorectal cancer.281

Cancers Associated with FAP and AFAP

The results of the COLARIS AP® test enable the development of a patient-specific medical management plan to significantly reduce the risk of cancer.

COLARIS AP will help you to:

  • Target increased surveillance and other interventions specifically to individuals with the APC or MYH gene mutations—maximizing patient care and increasing clinical efficiency
  • Improve patient compliance with tailored screening recommendations and preventive measures
  • Significantly improve outcomes and reduce medical costs through early diagnosis and treatment of cancer, should it develop
    • An individual’s risk for developing colorectal cancer can be reduced by nearly 100% with appropriate preventive measures in FAP86Avoid unnecessary interventions involving family members who do not test positive for the mutation(s)
  • Counsel patients and their family members on the underlying cause of the cancer or adenomas
  • Avoid unnecessary interventions involving family members who do not test positive for the mutation(s) known to be in the family
  • Differentiate between AFAP, MAP, and Lynch syndrome

It is possible to change the outcome for patients who have adenomatous polyposis syndromes. If a COLARIS AP® test result confirms the presence of adenomatous polyposis syndromes, the following medical management options may help reduce or even eliminate the risk of cancer.

Familial Adenomatous Polyposis (FAP)

Increase Surveillance:

  • Annual flexible sigmoidoscopy beginning between ages 10 and 1287
  • Following a prophylactic subtotal colectomy, flexible sigmoidoscopy of remaining ileal pouch and rectal epithelium every 6 months to 3 years, depending on number of polyps found on previous exam88,89
  • Esophagogastroduodenoscopy (EGD) every 1 to 4 years (depending on polyp burden), beginning between age 20 and 2590
  • Annual physical exam, including palpation of the thyroid, beginning between age 10 and 1290

Chemoprevention:

  • Research to determine the effectiveness of NSAIDS in colorectal polyp development is currently being conducted
  • The FDA has approved some NSAIDS to help prevent polyp formation in the rectum after a total colectomy, but none of these drugs are proven to reduce or prevent polyps prior to surgery

Surgical Management

  • Prophylactic total colectomy is advised following development of adenomatous polyps91

Note: Screening for other FAP/AFAP-associated cancers may be considered, depending on family history.

Attenuated FAP (AFAP)

Increased Surveillance:

  • Colonoscopy every 1 to 3 years, beginning in late teens or mid-twenties92
  • Esophagogastroduodenoscopy (EGD) every 1 to 4 years (depending on polyp burden), beginning between age 20 and 2590

Surgical Management:

  • Prophylactic colectomy, though it may not be necessary for an APC-positive patient, should be considered on an individual basis87

Note: Screening for other FAP/AFAP-associated cancers may be considered, depending on family history.

MYH-Associated Polyposis (MAP):

  • For patients who have MAP, medical society management recommendations include colonoscopies every 1-2 years starting at age 25-30, upper endoscopies every 3-5 years starting at age 30-35, and surgical considerations. The most appropriate medical management will vary based upon your patient’s clinical presentation.282
  • For MYH mutation carriers (1 mutation), medical management should be determined by clinical findings and personal and family history of colorectal polyps and/or cancer. Current data are limited but suggest that any increase in risk, if present, is likely to be small.283

Listed below are examples of the possible test results for COLARIS AP® genetic testing.

Comprehensive COLARIS AP APC Analysis and MYH Mutation Panel Result
Example of a patient positive for two copies of an MYH mutation
Comprehensive COLARIS AP APC Analysis and MYH Mutation Panel Result
Example of a patient with no mutation detected
Comprehensive COLARIS AP APC Analysis and MYH Mutation Panel Result
Example of a patient positive for an APC mutation
Comprehensive COLARIS AP APC Analysis and MYH Mutation Panel Result
Example of a patient with a genetic variant of uncertain significance in the APC gene
Comprehensive COLARIS AP MYH Analysis Result
Example of a patient with no mutation detected
Comprehensive COLARIS AP MYH Analysis Result
Example of a patient positive for one MYH mutation
Single Site COLARIS AP Analysis Result
Example of a patient negative for a specific mutation in the APC gene
Single Site COLARIS AP Analysis Result
Example of a patient positive for a specific mutation in the APC gene

Guidelines for Letters of Medical Necessity (LMNs)

A healthcare provider may include a LMN with a pre-authorization request, claim submission, or appeal to facilitate the insurance review process for the benefit of the patient. Our experience with insurance companies is such that we encourage healthcare providers to cover as many of the following points as possible that are applicable to the patient:

  • Explanation that the requested genetic test has been ordered by a physician
  • Explanation of the medical necessity for the test requested
  • If family history is cited, give as much family history as possible, including specifics about relationship to patient, cancer site, age of cancer diagnosis (alternatively, a detailed three-generation pedigree that contains this information could be attached and referred to in the body of the letter)
  • Patient’s diagnosis and prognosis, including age of onset and specific location of cancer
  • Explanation that the genetic test is recognized as appropriate for inclusion in this patient’s treatment regimen
  • Treatment plan, including specific statements about anticipated impact of the genetic test on the medical management of patient.

We remind you to read through the entire letter to make sure it makes sense for each patient. Please call 800-469-7423 if Myriad Customer Service may provide further assistance or answer questions.

Tips for Saving and Modifiying Sample LMNs:

This is a Microsoft Word document that is saved as “read-only” to preserve the original wording. To customize, simply use the “save as” command from the “File” menu, which will prompt you to rename the document to something besides the original name. Your newly named document is no longer “read-only” and can be modified as you wish.

COLARIS AP® Sample Family Letters

The following letters are examples of what your patients can write and send to their relatives with a copy of their COLARIS AP® test results.

How is the COLARIS AP test performed?

A small amount of blood is drawn from the patient and sent to Myriad Genetic Laboratories, Inc. for DNA sequencing analysis of the APC and MYH genes.  COLARIS AP can also detect large rearrangements in the APC gene that will not be identified by gene sequencing.

How long does it take for COLARIS AP test results?

Results take up to 21 days after insurance approval and are sent to the provider identified as “mail to” on the Test Request Form.

Will a patient's health insurance cover the test?

Most health insurance plans pay for COLARIS. Patients typically pay co-insurance of less than 10% of the test price. Myriad will notify you before processing your test if you total financial responsibility exceeds $375 (or $15 per month when utilizing our interest-free 25-month payment plan) for any reason, including co-insurance, deductible, or non-covered services. Call Myriad at 800-469-7423 for more details.

Can a health insurance provider discriminate against a patient based on COLARIS <em>AP</em> results?

Federal and state governments recognize the value of genetic information to patients and doctors and have put specific legal protections in place. The Genetic Information Nondiscrimination Act or GINA adds additional protection to existing legal protections that are in place at both the federal and state levels. GINA is a federal law that protects Americans from being treated unfairly based on differences in their DNA. GINA prevents discrimination from health insurers and employers. Health insurers are prohibited from requesting or requiring an individual or family member to undergo a genetic test or requesting, requiring, or purchasing genetic information, nor can they use an individual’s genetic information in setting eligibility, premium or contribution amounts by group and individual health insurers. GINA also protects individuals from employers requesting, requiring, or purchasing genetic information about an individual employee or family member. In addition, the employer is prohibited from using an individual’s genetic information in employment decisions such as hiring, firing, job assignments and promotions.

The Health Insurance Portability & Accountability Act (HIPAA) recognizes genetic information as Protected Health Information (PHI) and specifies protecting its confidentiality. HIPAA further states that “genetic information shall not be treated as a pre-existing condition in the absence of a diagnosis of the condition related to such information,” e.g., a diagnosis of hereditary cancer. The Americans with Disabilities Act (ADA) provides additional protections regarding the use of genetic information by employers.

Almost all states have additional laws that protect people from various forms of health insurance and employment discrimination based on genetic information. For more information about how these laws apply to you, go to the National Human Genome Research Institute.

If a patient has already been diagnosed with FAP or AFAP, what does a positive COLARIS AP result indicate?

Individuals with an APC mutation are at a greater risk for developing a new cancer – even extracolonic cancer following a prophylactic colectomy.  Knowing a patient’s genetic status can help reduce this risk or detect another potential cancer at an earlier, more treatable stage.  Importantly, a patient’s test results also have significant meaning for the health of his or her family members, especially since FAP is characterized by juvenile onset.  In addition, patients clinically diagnosed with FAP or AFAP may have mutations in their MYH genes, leading to a condition called MAP, which presents different risks to family members.  Genetic testing cane help distinguish between MAP and FAP/AFAP in certain families.

What are COLARIS[PLUS] and COLARIS AP [PLUS]

COLARISPLUS and COLARIS APPLUS are Comprehensive COLARIS and Comprehensive COLARIS AP plus MYH full sequencing and large rearrangements.

Will the price be increasing with the MYH enhancement?

No. There will be no price increase with the MYH enhancement.

Will this change impact insurance coverage for COLARIS and COLARIS AP?

No. Coverage for the COLARISPLUS and COLARIS APPLUS tests with MYH enhancements will be equivalent to the current coverage.

How will Medicare submissions be handled?

The process for Medicare submissions will not change for COLARISPLUS and COLARIS APPLUS. MYH will be run concurrently with MLH1, MSH2, MSH6, and EPCAM. PMS2 will continue to be run as a reflex test.

When will the MYH enhancement take effect?

All Comprehensive COLARIS and Comprehensive COLARIS AP orders received on or after February 6, 2013 will automatically include MYH analysis.

Will MYH analysis be run twice if I order both COLARIS[PLUS] and COLARIS AP[PLUS] testing?

No. MYH analysis will only be processed and reported once if both COLARISPLUS and COLARIS APPLUS testing are ordered, or if MYHgene analysis has been completed in the past.

Do I need to order MYH gene analysis on my patient if they had prior COLARIS or COLARIS AP testing and did not receive MYH full-sequencing and large rearrangement gene analysis?

MYH analysis should be ordered for previously tested patients at the discretion of the healthcare provider. To order MYH analysis for previously tested patients, write in “MYH analysis” in the “other” section of the COLARIS or COLARIS AP Test Request Form (TRF). MYH analysis test orders for previously tested patients will follow our normal customer service process. The cost of MYHanalysis when ordered independently is $1,340.

How do I manage patients who received a single MYH mutation result?

Medical management should be determined by clinicalfindings and personal and family history of colorectal polyps and/or cancer. Current data are limited but suggest that any increase in risk, if present, is likely to be small (N Engl J Med 2003;348:791-799; Lancet 2003;362:39-41; J Natl Cancer Inst 2004;96:1631-1634).

Will the MYH enhancements increase turn around time?

No. COLARISPLUS and COLARIS APPLUS will still be reported up to 21 days after insurance approval.

Will the MYH enhancements increase turn around time?

No. COLARISPLUS and COLARIS APPLUS will still be reported up to 21 days after insurance approval.

When will the new Test Request Forms (TRFs) with the COLARIS[PLUS] and COLARIS AP test offerings be distributed?

Test kits shipped after late February 2013 will contain new TRFs. However, Myriad will automatically include MYH analysis on all Comprehensive COLARIS or Comprehensive COLARIS AP orders processed on or after February 6, 2013.

How will the new enhancements be reported for COLARIS[PLUS] and COLARIS AP?

Similar to PMS2 analysis, MYH analysis will be reported on a separate page, in the same packet as COLARIS results report. MYHwill be reported on the same report for COLARIS APPLUS results.