Tests
KRAS-Variant
KRAS-Variant Test Populations
Women diagnosed with ovarian cancer*1,2
Independent of their BRCA1/BRCA2 mutational status, who:
- May wish to be tested to understand personal additional cancer risk3,4,5, and/or to understand the potential for familial genetic inheritance of risk for 1º or 2º relatives
- May wish to understand their platinum sensitivity or resistance 2
*epithelial ovarian/fallopian tube or primary peritoneal
Essential patient information: (1) ovarian cancer status including type; (2) pedigree if available; (3) BRCA1/BRCA2 test result if available, i.e. negative, positive – specify mutation or gene variant
Women who have been diagnosed with breast cancer4
Independent of their BRCA1/BRCA2 mutations status), who:
- May wish to be tested to aid in the estimation of modified personal future cancer risk5 and/or to understand the potential for familial genetic inheritance of risk for 1º or 2º relatives
Essential patient information: (1) breast cancer status including type when available; (2) pedigree if available; (3) BRCA1/BRCA2 test result if available, i.e. negative, positive – specify mutation or genetic variant
Women considered at increased risk for developing breast and/or ovarian cancer
because they have a history of endometriosis6, have had breast cancer personally4, are considering estrogen alterations such as hormone replacement therapy or anti-estrogen prevention therapy7,8, or are an unaffected 1º or 2º relative of an affected member of an HBOC family containing any of the following:
- 1 ovarian cancer in a 1º or 2º relative (as the patient would be clinically considered at risk despite limited family history)
- 1 individual with both breast cancer and ovarian cancer, or any other case of multiple primary cancer
- 2 or more individuals with breast cancer over 2 generations
Cancer patients
Individuals with primary or metastatic cancer of any type, to aid in insight into the efficacy of subsequent specific therapy.
Individuals with a Family History of Cancer
Individuals with a family history of breast, ovarian or lung cancer, or multiple primary cancer in any first or second degree relative.
NOTE: The Laboratory Director and/or Laboratory Supervisor will consult with the referring clinician and/or review all requisitions to confirm testing is being performed appropriately. In certain circumstances [i.e. small family size, families with a significantly biased number of male members] testing may be permitted as an exception to the criteria above. These criteria may be updated as additional data are obtained which better define the test populations that would benefit from KRAS-variant testing.
References:
- Ratner et al. A KRAS-variant is a biomarker of poor outcome, platinum chemotherapy resistance, and a potential target for therapy in ovarian cancer. Oncogene 2011; 1-8.
- Ratner E, Lu L, Boeke M, et al. A KRAS-variant in Ovarian Cancer Acts as a Genetic Marker of Cancer Risk. Cancer Research 2010; 15: 6509-15.
- Chin LJ, Ratner E et al. A SNP in a let-7 microRNA complementary site in the KRAS 3′ untranslated region increases non-small cell lung cancer risk. Cancer Research 2008 Oct 15; 68(20):8535-40.
- Paranjape T, Heneghan H, Lindner R, et al. A 3′-untranslated region KRAS-variant and triple-negative breast cancer: a case-control and genetic analysis. Lancet Oncology 2011.
- Pilarski et al. A KRAS-variant is Associated with Risk of Developing Double Primary Breast and Ovarian Cancer. PLos ONE; in press.
- Grechukhina et al. A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis. EMBO Molecular Medicine 2012; 4: 206-217.
- Cerne et al. KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study. BMC Cancer 2-12. 12:105.
- McVeigh et al. Estrogen Withdrawal, Increased Breast Cancer Risk, and the KRAS-variant. In press.