Comprehensive Cancer Susceptibility Testing
(BRCA 1 and 2 testing)

What is BRCA 1 and 2 testing?

Genetic and Lifetime Risks

The 46 genes analyzed by this testing fall into three groups: high risk, moderate risk, and new risk.

・High Risk Genes

Those with pathological mutations in high-risk genes have disease risks related to those genes at least four times greater than the general populations. Mutations on in high-risk genes lead to increased risk of developing cancer or tumors at an early age or developing multiple cancers throughout life.
High-risk genes include BRCA1, BRCA2 (BRCA-related breast or ovarian cancer syndrome); CDH1 (hereditary diffuse gastric cancer syndrome); EPCAM, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome); PALB2; PTEN (Cauden syndrome) Includes PTEN Hamatoma Tumor Syndrome); TP53 (Li-Fraumeni Syndrome).

Figure 1: Lifetime risk of breast and ovarian cancer in the presence of pathogenic mutations in high-risk genes

・Moderate Risk Genes

Mutations in moderate-risk genes lead to the person being two to four times more likely to develop cancer in their lifetime than in the general population.

・New Risk Genes

These are genes newly associated with the risk of cancer, whose exact role and results are not yet well-understood or fully studied.

In addition to Table 1, the Comprehensive Cancer Panel also tests the following genes: APC, AXIN2, BMPR1A, CDK4, CDKN2A, MUTYH, POLD1, POLE, SCG5 / GREM1, SMAD4, STK11, VHL.

Table 1: Lifetime risk of cancer (tumor) linked to genes associated with hereditary breast and ovarian cancer

Gene Lifetime Cancer and/or Tumor Risks
High Risk Genes BRCA1 Female breast (57-87%), Ovarian (24-54%), Prostate, Male breast, Pancreatic, Fallopian tube, Primary peritoneal, Endometrial
BRCA2 Female breast (41-84%), Prostate (20-34%), Ovarian (11-27%), Pancreatic, Male breast, Melanoma, Fallopian tube, Primary peritoneal, Endometrial
CDH1 Gastric cancer (40-83%), Female breast (39-52%), Colon

EPCAM,
MLH1,
MSH2,
MSH6,

PMS2

Colorectal (11-80%), Endometrial (12-61%), Ovarian (1-24%), Gastric (<1-20%), Urinary tract (1-10%), Pancreatic, Biliary tract, Small bowel, Brain, Sebaceous tumors

Tumor spectrum is representative of Lynch syndrome; data are limited with regard to the association of certain cancers with pathogenic variants in MSH6, PMS2 and EPCAM

PALB2 Female breast (25-58%), Male breast, Pancreatic, Ovarian
PTEN Thyroid (3-38%), Endometrial (5-28%), Colon, Renal, Melanoma, Gastrointestinal polyps
TP53

Female breast, Sarcoma-bone and soft tissue, Brain, Hematologic malignancies, Adrenocortical carcinoma, among others.
Overall risk for cancer: nearly 100% in females, 73% in males.

Moderate-Risk Genes ATM Female breast, Colon, Pancreatic
BRIP1 Ovarian, Female breast
CHEK2 Female breast, Male breast, Colon, Prostate, Thyroid, Endometrial, Ovarian
RAD51C Ovarian, Female breast
RAD51D Ovarian, Female breast
Newer-Risk Genes BARD1 Female breast, Ovarian
FANCC Female breast
NBN Female breast, Melanoma, Non-Hodgkin lymphoma

Sample Submission

The test will be performed from DNA from a buccal swab. A questionnaire, consent and request form needs to be filled out.

Results

It takes around 2~4 weeks for the results to come back. Most of the test results fall into 4 categories:

  1. Positive (pathogenic variant)
  2. Likely pathogenic variant
  3. Negative
  4. VUS-Variant of uncertain significance

Medical Management based on Genetic Test Results

Depending on your results, you will receive medical management for early detection or risk reduction. Medical management includes enhanced screening, risk reducing surgery and occasionally risk reducing medicine. The recommended screening would include MRI, mammogram, ultrasound, endoscopy, and biopsy, etc.

Limitations of the test

Even if you take this comprehensive test, there are lots of different types of cancers and you may still develop cancer in the future. In most cases, the risk for cancer is not expected to be greater than the general population with negative test results. Sometimes the result interpretation may be limited, if the gene is described as moderate-risk or newer-risk. Even with a negative result sometimes there are other genes that can explain the familial cancer, or areas of a gene that were not examined in the initial test. A genetic specialist or other healthcare provider can determine if further genetic testing is appropriate.

Merits of the Test

Usually most positive or likely pathogenic test results, first-degree relatives (parents, siblings, and children) have a 50% chance of having the same variant. Please remember that for most of these genes, not all people who inherit a pathogenic or likely pathogenic variant will develop cancer and/or tumours, however the chance is increased above that of the general population. In some cases, certain genes may also be associated with an autosomal recessive condition. Knowledge of a positive result provides valuable information to patients, healthcare providers, and family members, reduce risk or improve early detection. Also, testing family members may be appropriate and can allow for more accurate predictions of their cancer and/or tumour risks.

Cost

¥240,000 (With Tax:¥264,000)

An appointment is necessary for the test, so please ask the staff.
❈Price is subject to change without notice.