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General Information:

Breast cancer is one of the leading causes of premature deaths in women. Epidemiological studies show that in 36% of women diagnosed with breast cancer, especially under 30 years of age, the cancer may be associated with a genetic disorder. This situation increases the chances of early diagnosis of breast cancer clinically and increases the likelihood of treatment.

In breast cancer, the major genes that are thought to be caused about 5-10% by inherited factors are BRCA1, BRCA2. It is known that mutations in these genes with tumor suppression features are responsible for about 40% of inherited breast cancers.

  • Life-long risk of developing breast cancer in women is 1/8; ovarian cancer development risk is 1/70.
  • 5-10% of breast and ovarian cancers are familial.
Who should have mutation screening in BRCA1 and BRCA2 gene?
  • Women who are diagnosed with breast or ovarian cancer (to provide genetic counseling to the family)
  • Women who are diagnosed with ovarian cancer, whose first or second degree relatives have history of breast or ovarian cancer,
  • Women who are diagnosed with breast cancer before 50 years of age,
  • Women who have a history of ovarian cancer in their first or second degree relatives, or who have a male relative diagnosed with breast cancer,
  • Women with mutation in the BRCA1 or BRCA2 gene in their first or second degree relatives should have this screening done.

Women carrying the BRCA mutation were found to be associated with a 2.7 to 6.4 times increased life-long risk of breast cancer, and an increased risk of over-cancer at 9.3 to 35.3 times, compared to women at average risk.

  • The tumor suppressor genes, BRCA1 is located in the 17q21 region and the BRCA2 gene is localized in the 13q12.3 region. There genes are also responsible for DNA repair. Mutations detected on both genes lead to inherited breast cancer
  • BRCA1 and BRCA2 genes are responsible for 84% of inherited breast cancer and 90% of inherited ovarian cancer.
  • The life-long risk of developing breast cancer in a woman carrying a mutation in the BRCA1 gene is 50-80%
  • The life-long risk of developing breast cancer in a woman carrying a mutation in the BRCA2 gene is 50%.
  • The BRCA1 mutation increases the lifetime risk of ovarian cancer in women by 20-50%.
  • The BRCA2 gene mutation increases the life-long risk of ovarian cancer in women by 10-20%.
  • Breast cancer occurs in 6% of men with BRCA2 gene mutation
  • Over 1600 mutations for the BRCA1 gene and over 1800 mutations for the BRCA2 gene have been reported.
  • In women with mutations in the BRCA1 and BRCA2 genes, the risk of breast cancer is reduced by 90% with bilateral prophylactic mastectomy, while the risk of ovarian cancer is reduced by 90% and breast cancer by 50% with prophylactic oophorectomy.
  • With sequence analysis done in cancer patients using the Affymetrix GeneChip BRCA1-BRCA2 Resequencing Arrays, reported mutations can be identified for these genes responsible for breast cancer.
  • Genes, other than BRCA1 and BRCA2 genes, that have been reported to have effect in breast cancer can also be analyzed within the Affymetrix GeneChip BRCA1-BRCA2 Resequencing Arrays. These are;
  • TP53 (tumor protein p53)
  • PALB2 (partner and localizer of BRCA2)
  • CHEK2 [CHK2 checkpoint homolog (S. pombe)]
  • ATM (ataxia telangiectasia mutated)
  • PTEN (phosphatase and tensin homolog) genes.
  • In addition to early diagnosis of familial breast cancer being quickly and reliably possible with these Arrays, the possibility of early treatment of breast cancer also increases; and with the detected mutations in familial breast and/or ovarian cancers, it is possible to scan these mutations faster in other family members.
  • At the same time, detected mutations may form a basis for preimplantation genetic diagnosis.
Warnings and Ethics
  • This test should only be performed on the above indications
  • • Each individual has the right to have genetic testing for breast cancer, but they must be informed about hereditary cancers and about their responsibilities in sharing genetic results with their relatives at risk.
  • The penetration of the gene / genes to be screened for breast cancers and environmental factors must be taken into consideration. For this reason, the patient should be given genetic counselling before and after the test.
October 29, 2017 Genel
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