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

Study Overview
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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.

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

Conditions
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Cancer

Intervention / Treatment
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* Genetic: KRAS-variant and microRNA binding site mutation testing


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Family Registry<br>For individuals identified with the KRAS-variant. Patients will be prospectively followed to determine the impact of lifestyle on disease risk. | Genetic: KRAS-variant and microRNA binding site mutation testing<br>* Participant in these studies will be tested for the KRAS-variant<br>|
| KRAS-variant BRCA negative Breast Cancer<br>Women with breast cancer who are BRCA negative will be tested for the KRAS-variant, to determine the associations as well as the prevalence. | Genetic: KRAS-variant and microRNA binding site mutation testing<br>* Participant in these studies will be tested for the KRAS-variant<br>|
| Double primary breast cancer<br>Women with multiple primary breast cancer will be tested for the KRAS-variant and compared between those with this mutation and those without. | Genetic: KRAS-variant and microRNA binding site mutation testing<br>* Participant in these studies will be tested for the KRAS-variant<br>|
| Autoimmunity<br>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. | |

What is the study measuring?
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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 | 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. | 1 year | 
| Comparing the impact of interventions in KRAS-variant versus non-KRAS variant populations | 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. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The impact of lifestyle factors on cancer risk for KRAS-variant patients | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Cancer Risk, Family Breast and Ovarian Cancer, Genetic Cancer Risk, Cancer Treatment, Familial multiple primary cancer risk, Autoimmunity, Endometriosis