Home > Gynecology (Obstetrics) > Gynecological Examination:Comprehensive Cancer Susceptibility Testing


Gynecological Osaka (Obstetrics and Gynecology). Woman are very delicate.

Gynecological Examination

 

Comprehensive Cancer Susceptibility Testing (BRCA 1 and 2 testing)

What is BRCA 1 and 2 testing?

Most breast cancer and ovarian cancer is non-hereditary, however 10% of breast cancer and 25% of ovarian cancer is caused by a hereditary harmful change in a gene that increases the risk of developing cancer. BRCA 1 and 2 are the most known genes linked to breast cancer risk and can be inherited from either parent. The Comprehensive Common Cancer Panel analyses 46 genes including BRCA 1 and 2, but includes other pathogenic variants in other genes.

 

<Genes and Lifetime Risks>

These genes can be categorized into 3 main groups: High-Risk, Moderate-Risk and Newer-Risk.

 

•High-Risk Genes

Pathogenic variants in these genes are associated with an increased risk, more than 4-fold risk compared to the general population. Patients who have these mutations could develop cancer or tumours at a young age or have a higher risk of multiple cancers in their life time.
High-risk genes include BRCA1, BRCA2 (BRCA-Related Breast and/or Ovarian Cancer syndrome); CDH1 (Hereditary Diffuse Gastric Cancer syndrome); EPCAM, MLH1, MSH2, MSH6, PMS2 (Lynch syndrome); PALB2; PTEN (PTEN Hamartoma Tumor syndrome, including Cowden syndrome); and TP53 (Li-Fraumeni syndrome).

Figure 1: Lifetime Cancer and/or Tumor Risks for Genes Associated with Hereditary Breast and Ovarian Cancer

Figure 1: Lifetime Cancer and/or Tumor Risks for Genes Associated with Hereditary Breast and Ovarian Cancer

•Moderate-Risk Genes

These mutations in genes are associated with a 2-4 fold increase in risk of developing one or more cancers in their lifetime compared to the general population.

•Newer Risk Genes

Newly discovered gene variants associated with cancer risk have not yet been well studied but nonetheless identified. The Comprehensive Common Cancer Panel tests 46 genes: In addition, the following genes are also tested: APC, AXIN2, BMPR1A, CDK4, CDKN2A, MUTYH, POLD1, POLE, SCG5/GREM1, SMAD4, STK11, VHL.

Table 1: Lifetime Cancer and/or Tumor Risks for 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

Page Top

Sample Submission

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

Page Top

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

Page Top

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.

Page Top

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.

Page Top

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.

Page Top

Cost of the Test

¥240,000 plus tax.
An appointment is necessary for the test, so please ask the staff.

❈Price is subject to change without notice.

Page Top