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

Обзор

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.

Подробное описание

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.

Вмешательства

• Генная терапия KRAS-variant and microRNA binding site mutation testing
  Participant in these studies will be tested for the KRAS-variant

Первичные конечные точки

• Measuring the prevalence of the KRAS-variant in certain populations Prevalence of the KRAS-variant in BRCA negative breast cancer patients [Срок оценки: 1 year]
• Comparing the impact of interventions in KRAS-variant versus non-KRAS variant populations [Срок оценки: 1 year]

Вторичные конечные точки (1)

• The impact of lifestyle factors on cancer risk for KRAS-variant patients [Срок оценки: 10 years]

Критерии участия

Критерии включения

• Personal or family history of cancer
• Personal history of endometriosis, or autoimmunity

Критерии исключения

• Younger than 18
• Non-english speaking and unable to understand and sign the consent

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• MiraKind — Los Angeles

Публикации

• 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: 10.1158/10 PMID 25183481
• 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. E PMID 25081901
• 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. PMID 22662244
• 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. PMID 22307873
• 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 p PMID 22139083
• 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. PMID 24732316
• 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. PMID 21994416
• 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. PMID 21435948

Идентификаторы

NCT: NCT02253251 · Pro00009633

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗