Hereditary predisposition to colorectal cancer

Oncology – Hereditary predisposition
to colorectal cancer (HNPCC)

Live better, live longer

Colorectal cancer (CRC) affects 1 in 20 people during their lifetime. An estimated 25% of all CRC cases present a familial clustering of the disease suggesting a contribution of genetic factors among other risk factors, while approximately 5% of all CRC cases are purely hereditary.

Hereditary non-polyposis colorectal cancer, also known as Lynch syndrome (LS) accounts for the majority of these hereditary CRC cases (2-3% of overall CRC cases).

But diagnostic criteria are complex and several studies have reported a lack of sensitivity and specificity for the Amsterdam criteria and the revised Bethesda guidelines, which are typically used for the identification of LS patients. In addition, heterogeneous and overlapping phenotypes make it difficult to distinguish from other type of hereditary CRCs and decide which genes should be analyzed first.

Our next generation sequencing panel for CRC therefore aims at facilitating patient referral for molecular screening, while keeping costs at a reasonable level.

How does it work ?

Stage 1: Patient identification – Discussion of personnal and family history Eplanation of genetic testing options
Stage 2: Sample submission -The patient’s sample and necessary paperwork are sent to the laboratory
Stage 3: Genetic testing – At the laboratory, genetic testing for most genes includes next-generation sequencing and/or exon aray analysis
Stage 4: Genetic test results – Contains information on the results of the genetic test and available medical management options. The final report is sent to the ordering Incorpore specialist
Stage 5: Post-test discussion – Incorpore specialist discusses the test resutls, medical management options, and implication for family members with the patient

To whom it is recommended?

The CRC gene panel is recommended for patient whose diagnosis and/or family history is indicative of a suspicion of hereditary CRC. Such indications include :

Early age of cancer onset:

Patient diagnosed with CRC or endometrial cancer at an age < 50
Patient diagnosed with CRC at an age < 60 and MSI-H histology

Patient presenting multiple cumulative polyps:

>10 colorectal adenomatous polyps
Multiple gastrointestinal hamartomatous polyps

Patient with multiple related primary CRCs or other associated LS cancers

Patient fulfilling the revised Bethesda guidelines or from a family meeting the Amsterdam II criteria

Family history:

Patient with a family history of hereditary CRC, with or without a known mutation
Multiple close family members with CRC or other associated LS cancers

Test benefit

Targeted risk management & treatment guidance
The subsequent identification of affected relatives in families where a disease causing mutation has already been found. This would allow an earlier management of at-risk family members.

Risk Management

Management options include:

For Lynch Syndrome

Surveillance

Colon & rectum: Colonoscopy every 1-2 year(s), starting at age 20-25
Endometrium & ovary: Gynecologic cancer screening
Others:
› Esophagogastroduodenoscopy (EGD) including side-viewing examination every 1-2 year(s), starting at age 30-35
› Annual urinalysis starting at age 30-35
› Annual physical exam including screening for skin cancers

Prophylactic Surgical Options

Prophylactic colectomy in young CRC patients
Prophylactic hysterectomy and/or bilateral salpingo-oophorectomy, after childbearing is completed

For Familial Adenomatous Polyposis (FAP)

Surveillance

Colon & rectum: Colonoscopy every 1-2 year(s), starting at age 10-12
Others:
› EGD including side-viewing examination every 1-3 years, starting when colorectal polyposis is diagnosed or at age 20-25
› Annual physical exam including cervical ultrasonography, starting at age 25-30

Prophylactic Surgical Options

Prophylactic colectomy when polyps become unmanageable

For attenuated Familial Adenomatous Polyposis (aFAP)

Surveillance

Colon & rectum: Colonoscopy every 2 years, starting at age 18-20
Others:
› EGD including side-viewing examination every 1-3 years, starting when colorectal polyposis is diagnosed or at age 20-25
› Annual physical exam including cervical ultrasonography, starting at age 25-30

Prophylactic Surgical Options

Prophylactic colectomy when polyps become unmanageable

For MUTYH-Associated Polyposis

Surveillance

Colon & rectum: Colonoscopy every 2 years, starting at age 18-20
Others:
› EGD including side-viewing examination every 1-3 year(s), starting at age 20-25

Prophylactic Surgical Options

Prophylactic colectomy when polyps become unmanageable

For Peutz-Jeghers syndrome

Surveillance

Colon & rectum: Colonoscopy every 2-3 years, starting with symptoms or in late teens
Others:
› EGD including side-viewing examination every 2-3 years, starting at age 10
› Magnetic resonance cholangiopancreatography and/or endoscopic ultrasound of the pancreas every 1–2 years starting at age 30
› Annual mammogram and breast MRI starting at age 25
› Clinical breast exam starting at age 25
› Annual pelvic examination, Pap smear and transvaginal ultrasound starting at age 18 years
› Annual testicular exam starting at age 10

For Juvenile Polyposis syndrome

Surveillance

Colon & rectum: Colonoscopy every 2-3 years, starting with symptoms or in late teens
Others:
› Esophagogastroduodenoscopy every 1-3 years

What is investigated?

Panel composition

Cost: CHF 5’000

Technical Details

Methodology

Targeted capture of all coding exons and exon-intron boundaries followed by NGS.
Deletion and duplication assessed by MLPA (Multiplex ligation-dependent probe amplification)

TAT

5-6 weeks in average. Urgent testing is available upon request.

Oncology – Hereditary predisposition to colorectal cancer (HNPCC)

How does it work ?

To whom it is recommended?

What is investigated?

Technical Details

Oncology – Hereditary predisposition
to colorectal cancer (HNPCC)