Clinical Validation of the Role of microRNA Binding Site Mutations in Cancer Risk, Prevention and Treatment
January 21, 2025 updated by: MiraKind
The investigators will recruit and enroll individuals that may have the KRAS-variant or other microRNA binding site mutations to join registry studies.
The investigators will allow individuals to obtain their results through a physician at the completion of the studies.
The investigators current focus is cancer and autoimmunity.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
The investigators have identified germ-line microRNA binding site mutations that predict an increased risk of cancer, endometriosis and associated infertility, and unique tumor biology and response to treatment.
The goal of this protocol is to further determine the mechanisms of these mutations, such as the KRAS-variant, and their associations with human health, such as cancer.
The investigators will collect saliva samples from individual patients who are eligible and choose to enroll in these studies, to test for the KRAS-variant and/or other mutations under study.
With specific permission, the investigators will keep excess DNA to further investigate and discover additional similar mutations.
The investigators purpose is to have participants answer questionnaires about lifestyle factors in an ongoing manner, to understand the impact of different factors on cancer risk for patients with these mutations.
Study Type
Observational
Enrollment (Estimated)
15000
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Joanne Weidhaas, MDPhD
- Phone Number: 203-671-1308
- Email: joanne@mirakind.org
Study Contact Backup
- Name: Joanne Weidhaas
- Phone Number: 424-387-8100
- Email: Joanne@miradx.com
Study Locations
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California
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Los Angeles, California, United States, 90025
- Recruiting
- MiraKind
-
Contact:
- Joanne Weidhaas, MDPhD
- Phone Number: 203-671-1308
- Email: joanne@mirakind.org
-
Contact:
- Joanne Weidhaas
- Phone Number: 424-387-8100
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Sampling Method
Non-Probability Sample
Study Population
Breast and ovarian cancer patients and the family members of those that have the KRAS-variant from primarily the US.
Those with Autoimmunity.
Description
Inclusion Criteria:
- Personal or family history of cancer
- Personal history of endometriosis, or autoimmunity
Exclusion Criteria:
- Younger than 18
- Non-english speaking and unable to understand and sign the consent
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Family Registry
For individuals identified with the KRAS-variant.
Patients will be prospectively followed to determine the impact of lifestyle on disease risk.
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Participant in these studies will be tested for the KRAS-variant
|
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Double primary breast cancer
Women with multiple primary breast cancer will be tested for the KRAS-variant and compared between those with this mutation and those without.
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Participant in these studies will be tested for the KRAS-variant
|
|
Autoimmunity
We have shown that the KRAS-variant and other members of this genetic class of mutations associate with altered immunity, leading to immunosuppression as well as autoimmunity.
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Participant in these studies will be tested for the KRAS-variant
|
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Cancer patients receiving certain treatments
We have found that microRNA binding site mutations are predictive biomarkers of outcomes from cancer therapy, including response and toxicity.
We will enroll patients to further study and validate these findings.
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Participant in these studies will be tested for the KRAS-variant
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Measuring the prevalence of the KRAS-variant in certain populations Prevalence of the KRAS-variant in BRCA negative breast cancer patients
Time Frame: 1 year
|
The Prevalence of the KRAS-variant will be determined in specific populations, such as women with drug resistant endometriosis, or BRCA negative breast cancer.
The prevalence will be compared to extensive data on the expected and known prevalence of the KRAS-variant in non-diseased populations.
Statistical significance will be determined by Chi-squared analysis.
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1 year
|
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Comparing the impact of interventions in KRAS-variant versus non-KRAS variant populations
Time Frame: 1 year
|
We will compare the impact of specific treatment approaches for example in women with the KRAS-variant and double primary breast cancer, versus the interventions used in non-KRAS-variant double primary breast cancer patients.
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1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
The impact of lifestyle factors on cancer risk for KRAS-variant patients
Time Frame: 10 years
|
Individuals with the KRAS-variant will be prospectively followed, and lifestyle factors will be associated with changes in health, including cancer development.
Our goal is to compare baseline characteristics between individuals with the KRAS-variant who do, versus do not, develop cancer, for example.
|
10 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Joanne Weidhaas, MDPhD, MiraKind
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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, Bouche O, Piessevaux H, Tejpar S. 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):4499-4510. doi: 10.1158/1078-0432.CCR-14-0348.
- Pilarski R, Patel DA, Weitzel J, McVeigh T, Dorairaj JJ, Heneghan HM, Miller N, Weidhaas JB, Kerin MJ, McKenna M, Wu X, Hildebrandt M, Zelterman D, Sand S, Shulman LP. The KRAS-variant is associated with risk of developing double primary breast and ovarian cancer. PLoS One. 2012;7(5):e37891. doi: 10.1371/journal.pone.0037891. Epub 2012 May 25.
- Grechukhina O, Petracco R, Popkhadze S, Massasa E, Paranjape T, Chan E, Flores I, Weidhaas JB, Taylor HS. A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis. EMBO Mol Med. 2012 Mar;4(3):206-17. doi: 10.1002/emmm.201100200. Epub 2012 Feb 3.
- Ratner ES, Keane FK, Lindner R, Tassi RA, Paranjape T, Glasgow M, Nallur S, Deng Y, Lu L, Steele L, Sand S, Muller RU, Bignotti E, Bellone S, Boeke M, Yao X, Pecorelli S, Ravaggi A, Katsaros D, Zelterman D, Cristea MC, Yu H, Rutherford TJ, Weitzel JN, Neuhausen SL, Schwartz PE, Slack FJ, Santin AD, Weidhaas JB. A KRAS variant is a biomarker of poor outcome, platinum chemotherapy resistance and a potential target for therapy in ovarian cancer. Oncogene. 2012 Oct 18;31(42):4559-66. doi: 10.1038/onc.2011.539. Epub 2011 Dec 5.
- Lee LJ, Ratner E, Uduman M, Winter K, Boeke M, Greven KM, King S, Burke TW, Underhill K, Kim H, Boulware RJ, Yu H, Parkash V, Lu L, Gaffney D, Dicker AP, Weidhaas J. The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905. PLoS One. 2014 Apr 14;9(4):e94167. doi: 10.1371/journal.pone.0094167. eCollection 2014.
- Smits KM, Paranjape T, Nallur S, Wouters KA, Weijenberg MP, Schouten LJ, van den Brandt PA, Bosman FT, Weidhaas JB, van Engeland M. 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.
- Paranjape T, Heneghan H, Lindner R, Keane FK, Hoffman A, Hollestelle A, Dorairaj J, Geyda K, Pelletier C, Nallur S, Martens JW, Hooning MJ, Kerin M, Zelterman D, Zhu Y, Tuck D, Harris L, Miller N, Slack F, Weidhaas J. A 3'-untranslated region KRAS variant and triple-negative breast cancer: a case-control and genetic analysis. Lancet Oncol. 2011 Apr;12(4):377-86. doi: 10.1016/S1470-2045(11)70044-4. Epub 2011 Mar 22. Erratum In: Lancet Oncol. 2011 Jun;12(6):522.
- Hollestelle A, Pelletier C, Hooning M, Crepin E, Schutte M, Look M, Collee JM, Nieuwlaat A, Dorssers LC, Seynaeve C, Aulchenko YS, Martens JW, van den Ouweland AM, Weidhaas JB. Prevalence of the variant allele rs61764370 T>G in the 3'UTR of KRAS among Dutch BRCA1, BRCA2 and non-BRCA1/BRCA2 breast cancer families. Breast Cancer Res Treat. 2011 Jul;128(1):79-84. doi: 10.1007/s10549-010-1080-z. Epub 2010 Jul 30.
- Ratner E, Lu L, Boeke M, Barnett R, Nallur S, Chin LJ, Pelletier C, Blitzblau R, Tassi R, Paranjape T, Hui P, Godwin AK, Yu H, Risch H, Rutherford T, Schwartz P, Santin A, Matloff E, Zelterman D, Slack FJ, Weidhaas JB. A KRAS-variant in ovarian cancer acts as a genetic marker of cancer risk. Cancer Res. 2010 Aug 15;70(16):6509-15. doi: 10.1158/0008-5472.CAN-10-0689. Epub 2010 Jul 20.
- Chin LJ, Ratner E, Leng S, Zhai R, Nallur S, Babar I, Muller RU, Straka E, Su L, Burki EA, Crowell RE, Patel R, Kulkarni T, Homer R, Zelterman D, Kidd KK, Zhu Y, Christiani DC, Belinsky SA, Slack FJ, Weidhaas JB. A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. Cancer Res. 2008 Oct 15;68(20):8535-40. doi: 10.1158/0008-5472.CAN-08-2129.
- 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. 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):2230-2236. doi: 10.1093/annonc/mdu367. Epub 2014 Jul 31. Erratum In: Ann Oncol. 2015 May;26(5):1038-1039. doi: 10.1093/annonc/mdv140.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2014
Primary Completion (Estimated)
December 1, 2030
Study Completion (Estimated)
September 1, 2035
Study Registration Dates
First Submitted
September 25, 2014
First Submitted That Met QC Criteria
September 26, 2014
First Posted (Estimated)
October 1, 2014
Study Record Updates
Last Update Posted (Actual)
March 25, 2025
Last Update Submitted That Met QC Criteria
January 21, 2025
Last Verified
January 1, 2025
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- Pro00009633
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