Clinical Validation of the Role of microRNA Binding Site Mutations in Cancer Risk, Prevention and Treatment

NCT ID: NCT02253251

Last Updated: 2025-01-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

15000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-09-30

Study Completion Date

2035-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Family Registry

For individuals identified with the KRAS-variant. Patients will be prospectively followed to determine the impact of lifestyle on disease risk.

KRAS-variant and microRNA binding site mutation testing

Intervention Type GENETIC

Participant in these studies will be tested for the KRAS-variant

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.

KRAS-variant and microRNA binding site mutation testing

Intervention Type GENETIC

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.

KRAS-variant and microRNA binding site mutation testing

Intervention Type GENETIC

Participant in these studies will be tested for the KRAS-variant

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.

KRAS-variant and microRNA binding site mutation testing

Intervention Type GENETIC

Participant in these studies will be tested for the KRAS-variant

Interventions

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KRAS-variant and microRNA binding site mutation testing

Participant in these studies will be tested for the KRAS-variant

Intervention Type GENETIC

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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MiraKind

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joanne Weidhaas, MDPhD

Role: PRINCIPAL_INVESTIGATOR

MiraKind

Locations

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MiraKind

Los Angeles, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Joanne Weidhaas, MDPhD

Role: CONTACT

203-671-1308

Joanne Weidhaas

Role: CONTACT

424-387-8100

Facility Contacts

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Joanne Weidhaas, MDPhD

Role: primary

203-671-1308

Joanne Weidhaas

Role: backup

424-387-8100

References

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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.

Reference Type BACKGROUND
PMID: 25183481 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25081901 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22662244 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22307873 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22139083 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24732316 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21994416 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21435948 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20676756 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20647319 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18922928 (View on PubMed)

Related Links

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http://mirakind.org

non-profit running the study

Other Identifiers

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Pro00009633

Identifier Type: -

Identifier Source: org_study_id

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