MiraKind is conducting research studies to learn more about how lifestyle and environmental factors may impact cancer risk for individuals with the KRAS-variant, an inherited gene mutation associated with an increased risk of breast,1 ovarian,2,3 lung,4 as well as others cancers,5,6 and multiple cancers in the same individual.7,8 If your patient enrolls in a MiraKind study and elects to receive their KRAS-variant results, we will report the results directly to their physician of choice so that you and your patient can use the information to guide their healthcare decisions.
What can the KRAS-variant tell me about my patient’s health?
Women with a family history of breast or ovarian cancer who test positive for the KRAS-variant are at an increased risk of cancer and thus should be considered for advanced cancer screening such as MRI per the American Cancer Society and U.S. Preventive Services Task Force’s guidelines.
It is important to note that up to half of patients who qualify for BRCA testing and are negative based on family history have the KRAS-variant. In addition, KRAS-variant families may present with cancers other than just breast or ovarian, and are less likely to have early onset cancers. Because of this unique profile, many KRAS-variant individuals fall “under the radar” of qualifying for more advanced screening options despite being at increased risk of cancer. Though the KRAS-variant is not yet included in screening guidelines, a positive test result may serve as an important flag to get women evaluated for more advanced screening options.
For cancer survivors, the KRAS-variant is a strong predictor of a second, independent cancer,8,9 highlighting the need to follow such patients very closely.
In addition to advanced breast and gynecological screening, data has shown that estrogen withdrawal appears to be a risk for cancer development for women with the KRAS-variant.8 Thus, women undergoing oophorectomy, or peri-menopausal women considering the use of hormone replacement therapy, may benefit from being tested for the KRAS-variant as continuing estrogen may be beneficial.
Lastly, the KRAS-variant has been shown to be a strong predictive biomarker of response to cancer treatment across numerous cancer types, including colon cancer,9-23 head and neck cancer,24-26 ovarian cancer,2,3 and NSCLC.27,28 If you are considering different chemotherapeutic agents for a patient, knowing their KRAS-variant status can be useful to help illuminate the best choice. The following articles provide more information about the role of the KRAS-variant in predicting treatment response to various cancers, and more information about trials can be found at our sister organization, MiraDx.
How can I learn more about the KRAS-variant?
We welcome the opportunity to work with physicians who are interested in learning more about our research, in collaborating on a study, and/or in better understanding the health implications for patients who test positive for this marker. If you would like a MiraKind physician or representative to contact you, please contact us.
If you are a potential MiraKind participant, please feel free to pass on the below page to your physician, for them to learn more about this marker.
- 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.
- Caiola E, Rulli E, Fruscio R, Buda A, Broggini M, Marabese M. (2012). KRas-LCS6 polymorphism does not impact on outcomes in ovarian cancer. Am J Cancer Res. 2012;2(3):298-308. Epub 2012 Apr 21.
- 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.
- Graziano F, Canestrari E, Loupakis F, Ruzzo A, Galluccio N, Santini D, Rocchi M, Vincenzi B, Salvatore L, Cremolini C, Spoto C, Catalano V, D’Emidio S, Giordani P, Tonini G, Falcone A, Magnani M. (2010). Genetic modulation of the Let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan. Pharmacogenomics J. 2010 Oct;10(5):458-64. doi: 10.1038/tpj.2010.9. Epub 2010 Feb 23.
- Zhang W, Winder T, Ning Y, Pohl A, Yang D, Kahn M, Lurje G, Labonte MJ, Wilson PM, Gordon MA, Hu-Lieskovan S, Mauro DJ, Langer C, Rowinsky EK, Lenz HJ. (2011). A let-7 microRNA-binding site polymorphism in 3′-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy. Ann Oncol. 2011 Jan;22(1):104-9. doi: 10.1093/annonc/mdq315. Epub 2010 Jul 5.
- Ruzzo A, Canestrari E, Galluccio N, Santini D, Vincenzi B, Tonini G, Magnani M, Graziano F. Role of KRAS let-7 LCS6 SNP in metastatic colorectal cancer patients. Ann Oncol. 2011 Jan;22(1):234-5. doi: 10.1093/annonc/mdq472. Epub 2010 Oct 6.
- Zhang W, Labonte MJ, Lenz HJ. (20111). KRAS let-7 LCS6 SNP predicts cetuximab efficacy in KRASwt metastatic colorectal cancer patients: Does treatment combination partner matter? Ann Oncol. 2011 Feb;22(2):484-5. doi: 10.1093/annonc/mdq704. Epub 2011 Jan 28.
- Smits KM, Paranjape T, Nallur S, Wouters KA, Weijenberg MP, Schouten LJ, van den Brandt PA, Bosman FT, Weidhaas JB, van Engeland M. (2011). A let-7 microRNA SNP in the KRAS 3’UTR is prognostic in early-stage colorectal cancer. Clin Cancer Res. 2011 Dec 15;17(24):7723-31. doi: 10.1158/1078-0432.CCR-11-0990. Epub 2011 Oct 12.
- Ruzzo A, Graziano F, Vincenzi B, Canestrari E, Perrone G, Galluccio N, Catalano V, Loupakis F, Rabitti C, Santini D, Tonini G, Fiorentini G, Rossi D, Falcone A, Magnani M. (2012). High let-7a microRNA levels in KRAS-mutated colorectal carcinomas may rescue anti-EGFR therapy effects in patients with chemotherapy-refractory metastatic disease. Oncologist. 2012;17(6):823-9. doi: 10.1634/theoncologist.2012-0081. Epub 2012 May 14.
- Ryan BM, Robles AI, Harris CC. (2012). KRAS-LCS6 genotype as a prognostic marker in early-stage CRC–letter. Clin Cancer Res. 2012 Jun 15;18(12):3487-8; author reply 3489. doi: 10.1158/1078-0432.CCR-12-0250. Epub 2012 Jun 5.
- Kjersem JB, Ikdahl T, Guren T, Skovlund E, Sorbye H, Hamfjord J, Pfeiffer P, Glimelius B, Kersten C, Solvang H, Tveit KM, Kure EH. (2012). Let-7 miRNA-binding site polymorphism in the KRAS 3’UTR; colorectal cancer screening population prevalence and influence on clinical outcome in patients with metastatic colorectal cancer treated with 5-fluorouracil and oxaliplatin +/- cetuximab. BMC Cancer. 2012 Nov 20;12:534. doi: 10.1186/1471-2407-12-534.
- Sebio A, Paré L, Páez D, Salazar J, González A, Sala N, del Río E, Martín-Richard M, Tobeña M, Barnadas A, Baiget M. (2013). The LCS6 polymorphism in the binding site of let-7 microRNA to the KRAS 3′-untranslated region: its role in the efficacy of anti-EGFR-based therapy in metastatic colorectal cancer patients. Pharmacogenet Genomics. 2013 Mar;23(3):142-7. doi: 10.1097/FPC.0b013e32835d9b0b.
- Sha D, Lee AM, Shi Q, Alberts SR, Sargent DJ, Sinicrope FA, Diasio RB. (2014). Association study of the let-7 miRNA-complementary site variant in the 3′ untranslated region of the KRAS gene in stage III colon cancer (NCCTG N0147 Clinical Trial). Clin Cancer Res. 2014 Jun 15;20(12):3319-27. doi: 10.1158/1078-0432.CCR-14-0069. Epub 2014 Apr 11.
- Langevin SM, Christensen BC. (2014). Let-7 microRNA-binding-site polymorphism in the 3’UTR of KRAS and colorectal cancer outcome: a systematic review and meta-analysis. Cancer Med. 2014 Oct;3(5):1385-95. doi: 10.1002/cam4.279. Epub 2014 Jun 2. Review.
- Saridaki Z, Weidhaas JB, Lenz HJ, Laurent-Puig P, Jacobs B, De Schutter J, De Roock W, Salzman DW, Zhang W, Yang D, Pilati C, Bouché O, Piessevaux H, Tejpar S. (2014). A let-7 microRNA-binding site polymorphism in KRAS predicts improved outcome in patients with metastatic colorectal cancer treated with salvage cetuximab/panitumumab monotherapy. Clin Cancer Res. 2014 Sep 1;20(17):4499-510. doi: 10.1158/1078-0432.CCR-14-0348.
- Sclafani F, Chau I, Cunningham D, Peckitt C, Lampis A, Hahne JC, Braconi C, Tabernero J, Glimelius B, Cervantes A, Begum R, Gonzalez De Castro D, Hulkki Wilson S, Eltahir Z, Wotherspoon A, Tait D, Brown G, Oates J, Valeri N. (2015). Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial. Ann Oncol. 2015 Sep;26(9):1936-41. doi: 10.1093/annonc/mdv285. Epub 2015 Jul 10.
- Dai Q, Wei HL, Huang J, Zhou TJ, Chai L, Yang ZH. (2016). KRAS polymorphisms are associated with survival of CRC in Chinese population. Tumour Biol. 2016
- Christensen BC, Moyer BJ, Avissar M, Ouellet LG, Plaza SL, McClean MD, Marsit CJ, Kelsey KT. (2009). A let-7 microRNA-binding site polymorphism in the KRAS 3′ UTR is associated with reduced survival in oral cancers. Carcinogenesis. 2009 Jun;30(6):1003-7. doi: 10.1093/carcin/bgp099. Epub 2009 Apr 20.
- Santiago MB, DE Lima Marson FA, Secolin R, Ribeiro JD, Lima CS, Bertuzzo CS. (2014). SLC23A2-05 (rs4987219) and KRAS-LCS6 (rs61764370) polymorphisms in patients with squamous cell carcinoma of the head and neck. Oncol Lett. 2014 Jun;7(6):1803-1811. Epub 2014 Apr 3.
- De Ruyck K, Duprez F, Ferdinande L, Mbah C, Rios-Velazquez E, Hoebers F, Praet M, Deron P, Bonte K, Speel EJ, Libbrecht L, De Neve W, Lambin P, Thierens H. (2014). A let-7 microRNA polymorphism in the KRAS 3′-UTR is prognostic in oropharyngeal cancer. Cancer Epidemiol. 2014 Oct;38(5):591-8. doi: 10.1016/j.canep.2014.07.008. Epub 2014 Aug 12.
- Chung CH, Lee JW, Slebos RJ, Howard JD, Perez J, Kang H, Fertig EJ, Considine M, Gilbert J, Murphy BA, Nallur S, Paranjape T, Jordan RC, Garcia J, Burtness B, Forastiere AA, Weidhaas JB. (2014). A 3′-UTR KRAS-variant is associated with cisplatin resistance in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann Oncol. 2014 Nov;25(11):2230-6. doi: 10.1093/annonc/mdu367. Epub 2014 Jul 31. Erratum in: Ann Oncol. 2015 May;26(5):1038-9.
- Nelson HH, Christensen BC, Plaza SL, Wiencke JK, Marsit CJ, Kelsey KT. (2009). KRAS mutation, KRAS-LCS6 polymorphism, and non-small cell lung cancer.
Lung Cancer. 2010 Jul;69(1):51-3. doi: 10.1016/j.lungcan.2009.09.008. Epub 2009 Oct 24.
- Ganzinelli M, Rulli E, Caiola E, Garassino MC, Broggini M, Copreni E, Piva S, Longo F, Labianca R, Bareggi C, Fabbri MA, Martelli O, Fagnani D, Locatelli MC, Bertolini A, Valmadre G, Pavese I, Calcagno A, Sarobba MG, Marabese M. (2015). Role of KRAS-LCS6 polymorphism in advanced NSCLC patients treated with erlotinib or docetaxel in second line treatment (TAILOR). Sci Rep. 2015 Nov 17;5:16331. doi: 10.1038/srep16331.