Individuals with certain genetic mutations associated with a higher risk of disease can make medical and lifestyle decisions to mitigate that risk.
We study microRNA-disrupting mutations which function in ways distinct from other known, inherited genetic markers. Our goal is to bring this new class of genetic differences into current prevention strategies. Our first example, the KRAS-variant, is an inherited genetic mutation associated with a family history of cancer, especially breast,1 ovarian,2 lung,3 as well as other cancers,4,5 and multiple cancers in the same individual.6,7
We have done extensive work to help people with the KRAS-variant mitigate their elevated cancer risk.
The latest research indicates the KRAS-variant’s unique biology shows great potential for disease prevention because it can be influenced by certain exposures, particularly hormones. Also, the KRAS-variant is primarily associated with cancer onset at or after menopause. Understanding these two factors provides some guidance for disease risk mitigation to individuals with the KRAS-variant.
Learning whether you carry this the KRAS-Variant can help you make informed decisions about your health at many points in your life:
Determine whether higher-level breast cancer screening, such as breast MRI, is something to consider in addition to annual mammograms. If having a hysterectomy and you are peri-menopausal, discuss the pros and cons of ovary removal with follow-up hormone replacement therapy (HRT) with your physician.
Determine whether hormone replacement therapy at menopause could be protective against cancer if not otherwise contraindicated. Use the information to determine whether or not ovary removal makes sense for you at menopause.
Be aware that an increased risk of ovarian cancer increases the importance of ongoing gynecological care. Determine whether continuing on hormone replacement therapy may be beneficial.
Use your genetic information to ask for continued breast and gynecological screening. Determine whether continuing on hormone replacement therapy may be beneficial.
- 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.
- Pilarski, R., Patel, D., Weitzel, J., McVeigh, T., Dorairaj, J., Heneghan, H., Miller, N., Weidhaas, J., Kerin, M., McKenna, M., et al. (2012). A KRAS-variant is associated with risk of developing double primary breast and ovarian cancer. PLos ONE 7, e37891.
- 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.