What it is & What we know
The KRAS-variant is an inherited genetic mutation associated breast cancer,1 ovarian cancer,4 lung cancer,5 as well as other cancers,6,7 and multiple cancers in the same individual.8,9
Genes and Gene Mutations
Our DNA is made up of thousands of genes which contain the instructions for how to make the proteins that regulate our bodies, telling our cells when to replicate, repair themselves, and/or destroy damaged cells.
Genes behave abnormally when they have mutated in some way and therefore cannot receive or send instructions properly.
Gene mutations can either be inherited or acquired (somatic). Inherited gene mutations are passed down from your mother and/or father, and are in every cell in your body when you are born. Acquired or somatic gene mutations occur after you are born and can result from environmental or lifestyle factors such as smoking, radiation, UV exposure, diet, etc.
Cancer is a disease that results in abnormal gene function.
While it has been believed that much of the time cancer is due to chance, as only 5-10% of cancers had known hereditary causes, we believe that much more of cancer risk is passed down from your parents. Our work at MiraKind is to discover the genetic markers for many more cancers, and to use this information to define the strategies and behaviors that may help reduce cancer risk.
The KRAS-variant is a good example of a new biomarker which provides a new explanation for the genetic cause of cancer for many more families with strong cancer histories. This mutation predicts an increased risk of breast (up from 1:8 to 1:4), ovarian (up from 1:74 to 1:12), and lung cancer, as well as multiple cancers in the same individual. The KRAS-variant is found in up to 25% of cancer patients, and is in 1/17 people in the general population, making it far more common that previously known mutations associated with cancer, such as BRCA1, which is found in only 5% of breast and ovarian cancer patients, and in 1/400 people overall.
Before the KRAS-variant
After the KRAS-variant
Hereditary cancer is caused by known inherited genetic mutations such as BRCA or CHEK2; familial cancer is cancer that occurs in families more often than would be expected by chance, although there has been no known genetic mutation identified to explain it; sporadic cancer is the term used to explain cancer that occurs in people who do not have a known strong family history or a known inherited genetic difference. The KRAS-variant is emerging as a hereditary explanation for a significant proportion of both familial and sporadic cancers that were previously unexplained.
What can the KRAS-variant tell me about my health?
The KRAS-variant was discovered in 2007, and MiraKind’s research studies are helping us learn more about its implications for health and cancer risk every day. However, we have already learned some important things about how individuals with the KRAS-variant may be able to use information about their KRAS-variant status to help them make decisions about their health. Learn more about the KRAS-variant if you have a family or personal history of cancer, have tested BRCA-negative, or are peri- or menopausal.
Getting tested for the KRAS-variant provides information that you and your doctor can use to make informed decisions about your health. If you do test positive, we are here to work with you and your physician—you can learn more about what your KRAS-variant test result means for your health in Understanding Your Results. As well, MiraKind’s community is available to provide ongoing support, communication, and education to you and your family members.
Why join a study?
By joining a MiraKind study, you can play a role in helping MiraKind answer some of the most pressing questions associated with cancer risk for individuals with the KRAS-variant. We are on a mission to better understand the behaviors, environmental factors, and lifestyle choices that can influence an individual’s risk of cancer, and your participation in a study helps us get closer to finding the answers to improve health for all individuals with the KRAS-variant, as well as to understand new mutations like the KRAS-variant.
We are currently looking for women 35 years or older to further understand how hormone replacement therapy (HRT) decreases the risk of cancer in women with the KRAS-variant, and to identify other women for whom HRT may impact cancer risk.
Learn more about participating in a MiraKind study here.
- McVeigh TP, Jung SY, Kerin MJ, Salzman DW, Nallur S, Nemec AA, Dookwah M, Sadofsky J, Paranjape T, Kelly O, Chan E, Miller N, Sweeney KJ, Zelterman D, Sweasy J, Pilarski R, Telesca D, Slack FJ, Weidhaas JB. (2015). Estrogen withdrawal, increased breast cancer risk and the KRAS-variant. Cell Cycle. 2015;14(13):2091-9. doi: 10.1080/15384101.2015.1041694. Epub 2015 May 11.
- Cerne JZ, Stegel V, Gersak K, Novakovic S. (2012). KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study. BMC Cancer. 2012 Mar 22;12:105. doi: 10.1186/1471-2407-12-105.
- Cerne JZ, Pohar-Perme M, Cerkovnik P, Gersak K, Novakovic S. (2015). Functional variants in CYP1B1, KRAS and MTHFR genes are associated with shorter telomere length in postmenopausal women. Mech Ageing Dev. 2015 Jul;149:1-7. doi: 10.1016/j.mad.2015.05.003. Epub 2015 May 15.
- Paranjape, T., Heneghan, H., Lindner, R., Keane, F., Hoffman, A., Hollestelle, A., Dorairaj, J., Geyda, K., Pelletier, C., Nallur, S., et al. (2011). A 3'-untranslated region KRAS variant and triple-negative breast cancer: a case-control and genetic analysis. Lancet Oncology 12, 377-386.
- Ratner, E., Lu, L., Boeke, M., Barnett, R., Nallur, S., Chin, L., Pelletier, C., Blitzblau, R., Tassi, R., Paranjape, T., et al. (2010). A KRAS-variant in Ovarian Cancer Acts as a Genetic Marker of Cancer Risk. Cancer Research 15, 6509-6515.
- Chin, L., Ratner, E., Leng, S., Zhai, R., Nullur, S., Babar, I., Muller, R., Straka, E., Su, L., Burki, E., et al. (2008). A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. Cancer Res 68, 8535-8540.
- Kazmi HR, Chandra A, Kumar S, Satyam LK, Gupta A, Nigam J, Srivastava M, Mittal B. (2016) A let-7 microRNA binding site polymorphism in the KRAS 3’UTR is associated with increased risk and reduced survival for gallbladder cancer in North Indian population. J Cancer Res Clin Oncol. 2016 Sep 12. [Epub ahead of print]
- Gutiérrez-Malacatt H, Ayala-Sanchez M, Aquino-Ortega X, Dominguez-Rodriguez J, Martinez-Tovar A, Olarte-Carrillo I, Martinez-Hernandez A, C CC, Orozco L, Cordova EJ. (2016) The rs61764370 Functional Variant in the KRAS Oncogene is Associated with Chronic Myeloid Leukemia Risk in Women. Asian Pac J Cancer Prev. 2016;17(4):2265-70.