A Novel Molecular Approach to Blood DNA Screening for Cancer: Specificity Assessment (The NOMAD Study)

PRIMARY OBJECTIVES:

I. To assess blood level distributions of candidate methylated DNA tumor markers across a cohort of patients without known cancer or precancer and, thereby, to estimate specificity cutoffs across a range of percentiles.

II. To evaluate the effects on marker levels (or test specificity) of selected demographic, exposure, medication, and chronic disease covariates.

III. To build a biospecimen archive to facilitate assessment of clinical specificity in future molecular blood test studies or appraisal of test refinements.

IV. Assess feasibility for detection of cancer using urine samples to assay MDMs, RNA or protein in cell free or extra-cellular vesicles.

V. Assess feasibility for detection of cancer using saliva to assay MDMs, RNA or protein in cell free or extra-cellular vesicles.

Inclusion criteria

• 10,000 patients without a known internal (non-cutaneous) cancer or a history of an internal cancer

• To balance age, rough recruitment goals will be set for the following subsets: 18-39 years, 40-49 years , 50-59 years , 60-69 years , 70-79 years , and >= 80 years
• To balance sex, roughly half of the participants recruited within each age subset will be women
• Roughly half of all participants will have had a colonoscopy or colon x-ray within the past 5 years, or Cologuard® test in the last 3 years which were negative for cancer and precancerous lesions
• Roughly half of all participants will have had a chest x-ray within the past 5 years which was negative for cancer
• Roughly half of women participants will have had a mammography in the past 5 years which was negative for cancer
• An attempt will be made to recruit minimums (parentheses) of the following subsets: men with normal Prostate-specific antigen (PSA) level (200); diabetes mellitus (200); connective tissue diseases like rheumatoid arthritis, systemic lupus erythematosus, and scleroderma (100); chronic obstructive lung disease (100); inflammatory bowel disease or cirrhosis (100), and pancreatitis (100)
• To assess the effects of other common covariates, specific recruitment targets will not be set. Rather, data obtained on all participants will include BMI, smoking (past/present), alcohol consumption, pregnant status (women), and selected medications (steroidal and non-steroidal anti-inflammatory drugs, statins, anti-hypertensives, and anti-depressants)

Exclusion criteria

• Patients has a past or current diagnosis of invasive cancer (this does not include basal cell or squamous cell skin cancers)
• Patient has had a solid organ transplant
• Inability to give informed consent

URINE EXCLUSIONS

• Patient has transurethral instrumentation (cystoscopy, placement of urinary catheter) within the 7 days prior to sample collection
• Patient has chronic indwelling urinary catheter
• Patient has had a urinary tract infection within the 14 days prior to sample collection

SALIVA EXCLUSIONS

• Patient has known clinically significant xerostomia
• Patient has known recent (within 30 days prior to collection) active upper respiratory tract infection or anogenital infection