GRAIL is using deep sequencing of circulating cell-free nucleic acids (cfNAs) to develop assays to detect cancer early in blood. The purpose of this study is to collect biological samples from participants with a new diagnosis of cancer (blood and tumor tissue) and from participants who do not have a diagnosis of cancer (blood) in order to characterize the population heterogeneity in cancer and non-cancer participants and to develop models for distinguishing cancer from non-cancer.

This is a prospective, multi-center, observational study with collection of de-identified biospecimens and clinical data from at least 15,000 participants from clinical networks in the United States and Canada. The study will enroll approximately 10,500 cancer participants (CANCER arm) and approximately 4,500 representative participants without a clinical diagnosis of cancer (NON-CANCER arm). Clinical information, demographics, and medical data relevant to cancer status are collected from all participants and their medical record at baseline (time of biospecimen collection), and subsequently from the medical record at intermittent future time points, at least annually for up to 5 years.

Inclusion Criteria for Non-Cancer Arm Participants:

• Age 20 years or older
• Able to provide a written informed consent

Exclusion Criteria for Non-Cancer Arm Participants:

• Known current or prior diagnosis of cancer except non-melanoma skin cancer
• Oral or IV corticosteroid use in past 14 days prior to blood draw
• Pregnancy (by self-report)
• Current febrile illness
• Acute exacerbation or flare of an inflammatory condition requiring escalation in medical therapy within 14 days prior to blood draw.
• Recipient of organ transplant or prior non-autologous (allogeneic) bone marrow or stem cell transplant
• Poor health status or unfit to tolerate blood draw

Inclusion Criteria for Cancer Arm Participants:

• Age 20 years or older
• Able to provide a written informed consent

Have either of the following:

A. Confirmed cancer diagnosis (any stage I-IV, as well as carcinoma in situ (CIS) within 90 days prior to or up to 42 days after study blood draw, based upon assessment of a pathological specimen

OR

B. A high suspicion for a cancer diagnosis by clinical and/or radiological assessment, with planned biopsy or surgical resection to establish a definitive diagnosis within 6 weeks (42 days) after study blood draw

Exclusion Criteria for Cancer Arm Participants:

• Known prior diagnosis of cancer except non-melanoma skin cancer
• Currently receiving, or ever received, any of the following therapies to treat their current cancer: surgical management of the cancer beyond that required to establish the cancer diagnosis; local, regional or systemic chemotherapy including chemoembolization; targeted therapy, immunotherapy including cancer vaccines; hormone therapy; or radiation therapy
• Pregnancy (by self-report)
• Current febrile illness
• Acute exacerbation or flare of an inflammatory condition requiring escalation in medical therapy within 14 days prior to blood draw.
• Recipient of organ transplant or prior non-autologous (allogeneic) bone marrow or stem cell transplant
• Poor health status or unfit to tolerate blood draw

Eligible study participants will be recruited from participating medical centers in a ratio of 3 non-cancer participants for every 7 cancer participants within each individual research center. Non-cancer subject recruitment will be monitored to achieve demographic characteristics (eg, age, gender, ethnicity, smoking status) reflective of those of the cancer participants.