Yes, cancer is a genetic disease. It is caused by changes in genes that control the way cells grow and multiply. Cells are the building blocks of your body. Each cell has a copy of your genes, which act like an instruction manual.

Genes are sections of DNA that carry instructions to make a protein or several proteins. Scientists have found hundreds of DNA and genetic changes (also called variants, mutations, or alterations) that help cancer form, grow, and spread.

Cancer-related genetic changes can occur because:

• random mistakes in our DNA happen as our cells multiply
• our DNA is altered by carcinogens in our environment, such as chemicals in tobacco smoke, UV rays from the sun, and the human papillomavirus (HPV)
• they were inherited from one of our parents

DNA changes, whether caused by a random mistake or by a carcinogen, can happen throughout our lives and even in the womb. While most genetic changes aren’t harmful on their own, an accumulation of genetic changes over many years can turn healthy cells into cancerous cells. The vast majority of cancers occur by chance as a result of this process over time.

An oncogene is a mutated gene that has the potential to cause cancer. Before an oncogene becomes mutated, it is called a proto-oncogene, and it plays a role in regulating normal cell division. Cancer can arise when a proto-oncogene is mutated, changing it into an oncogene and causing the cell to divide and multiply uncontrollably. Some oncogenes work like an accelerator pedal in a car, pushing a cell to divide again and again. Others work like a faulty brake in a car parked on a hill, also causing the cell to divide unchecked.

The name of oncogene suggests it is a gene that can cause cancer. Initially, oncogenes were identified in viruses, which could cause cancers in animals. Later, it was found that oncogenes can be mutated copies of certain normal cellular genes also called proto-oncogenes. Intact proto-oncogenes play important functions, regulating normal cellular growth, division, and apoptosis, which is the name for programmed or controlled cell death. Oncogenes or mutated copies of the proto-oncogenes may lead to uncontrolled cell growth and the escape from cell death, which may result in cancer development.

Paul P. Liu, M.D., Ph.D., Senior Investigator, Translational and Functional Genomics Branch

A tumor suppressor gene encodes a protein that acts to regulate cell division, keeping it in check. When a tumor suppressor gene is inactivated by a mutation, the protein it encodes is not produced or does not function properly, and as a result, uncontrolled cell division may occur. Such mutations may contribute to the development of a cancer.

Tumor Suppressor Gene. Tumor suppressor genes are present in all cells in our body. When they are switched on, they prevent ourselves from growing and dividing. You can think of them as being like the brakes of a car. However, when a tumor suppressor gene is switched off, either because the cell mistakenly deletes it or mutates it, the brake is released and the cell may start to grow and divide uncontrollably and potentially drive the cell to turn into a cancer cell.

Daphne W. Bell, Ph.D., Senior Investigator, Cancer Genetics and Comparative Genomics Branch

How Cancer Begins

Cancer begins when a cell undergoes a mutation, that is, one or more of its genes is damaged or lost. Mutations can occur when a cell is reproducing, but it's not easy for a cell to become cancerous. About six different mutations have to happen before the cell becomes a cancer cell. And, if a cell carries a mutation, it usually either destroys itself or is recognized as being abnormal by the immune system and killed. This is why cancer usually occurs in older people: there has been more time for exposure to carcinogens and for chance mutations to occur.

Genes at Risk

There are three different types of genes that can have an important part in making a cell turn malignant:

• Oncogenes ("cancer genes") encourage the cell to multiply. Normally, in adults, cells divide only rarely, for instance to replace cells damaged by a wound. If these genes become abnormal, however, they can instruct the cell to multiply without stopping, protect it against programmed cell death, and give it the ability to live in diverse tissues.
• Tumor-suppressor genes tell the cell to stop multiplying. If a tumor-suppressor gene is damaged, the cell won't receive the instruction to stop doubling and will multiply without stopping. This infinite lifespan is one of the hallmarks of a cancer cell. The best-known tumor-suppressor gene is called p53. p53 is damaged or missing in most human cancers.
• DNA repair genes repair damage to the DNA of other cells' genes. If the repair genes themselves are damaged, other mutations aren't repaired and the abnormal cell copies its mutations into its daughter cells.

How Genes Are Damaged

Genes become damaged in several ways:

• Damage due to free radicals produced in the normal process of metabolism
• Exposure to carcinogens, such as radiation, chemicals, tobacco, and infectious agents
• Random errors in DNA replication
• Inherited mutated gene

Genetic Predisposition

People who are said to have a genetic predisposition to certain types of cancer have a greater chance of developing that cancer than other people. This is because they were born with one of the mutations that can lead to a cell becoming cancerous. They may never develop that cancer, because the further mutations that cause the cancer may never take place. But they are at higher risk, because fewer mutations need to take place in their genes for the disease to arise.

A tumor marker is anything present in or produced by cancer cells or other cells of the body in response to cancer or certain benign (noncancerous) conditions that provides information about a cancer, such as how aggressive it is, whether it can be treated with a targeted therapy, or whether it is responding to treatment.

Listed below are tumor markers that are in common use, mainly to determine treatment or to help make a diagnosis of cancer. New tumor markers frequently become available and may not be reflected on this list.

This list does not include the many tumor markers that are tested by immunophenotyping and immunohistochemistry to help diagnose cancer and to distinguish between different types of cancer. Some tumor markers listed below are targets for targeted therapy in multiple cancers but serve as tumor markers for only a subset of cancers.

ALK gene rearrangements and overexpression

Cancer types or cancer-like conditions: Non-small cell lung cancer, anaplastic large cell lymphoma, histiocytoses
What's analyzed: Tumor
How used: To help determine treatment and prognosis

Alpha-fetoprotein (AFP)

Cancer types: Liver cancer and germ cell tumors
What's analyzed: Blood
How used: To help diagnose liver cancer and follow response to treatment; to assess stage, prognosis, and response to treatment of germ cell tumors

B-cell immunoglobulin gene rearrangement

Cancer type: B-cell lymphoma
What's analyzed: Blood, bone marrow, or tumor tissue
How used: To help in diagnosis, to evaluate effectiveness of treatment, and to check for recurrence

BCL2 gene rearrangement

Cancer types: Lymphomas, leukemias
What’s analyzed: Blood, bone marrow, or tumor tissue
How used: For diagnosis and planning therapy

Beta-2-microglobulin (B2M)

Cancer types: Multiple myeloma, chronic lymphocytic leukemia, and some lymphomas
What's analyzed: Blood, urine, or cerebrospinal fluid
How used: To determine prognosis and follow response to treatment

Beta-human chorionic gonadotropin (Beta-hCG)

Cancer types: Choriocarcinoma and germ cell tumors
What's analyzed: Urine or blood
How used: To assess stage, prognosis, and response to treatment

Bladder Tumor Antigen (BTA)

Cancer types: Bladder cancer and cancer of the kidney or ureter
What's analyzed: Urine
How used: As surveillance with cytology and cystoscopy of patients already known to have bladder cancer

BRCA1 and BRCA2 gene mutations

Cancer types: Ovarian and breast cancers
What's analyzed: Blood and/or tumor
How used: To help determine treatment

BCR-ABL fusion gene (Philadelphia chromosome)

Cancer types: Chronic myeloid leukemia, acute lymphoblastic leukemia, and acute myelogenous leukemia
What's analyzed: Blood or bone marrow
How used: To confirm diagnosis, predict response to targeted therapy, help determine treatment, and monitor disease status

BRAF V600 mutations

Cancer types or cancer-like conditions: Cutaneous melanoma, Erdheim-Chester disease, Langerhans cell histiocytosis, colorectal cancer, and non-small cell lung cancer
What's analyzed: Tumor
How used: To help determine treatment

C-kit/CD117

Cancer types: Gastrointestinal stromal tumor, mucosal melanoma, acute myeloid leukemia, and mast cell disease
What's analyzed: Tumor, blood, or bone marrow
How used: To help in diagnosis and to help determine treatment

CA15-3/CA27.29

Cancer type:Breast cancer
What's analyzed:Blood
How used:To assess whether treatment is working or if the cancer has recurred

CA19-9

Cancer types: Pancreatic, gallbladder, bile duct, and gastric cancers
What's analyzed:Blood
How used:To assess whether treatment is working

CA-125

Cancer type: Ovarian cancer
What's analyzed: Blood
How used:To help in diagnosis, assessment of response to treatment, and evaluation of recurrence

CA 27.29

Cancer type: Breast cancer
What's analyzed:Blood
How used:To detect metastasis or recurrence

Calcitonin

Cancer type:Medullary thyroid cancer
What's analyzed:Blood
How used:To aid in diagnosis, check whether treatment is working, and assess recurrence

Carcinoembryonic antigen (CEA)

Cancer types:Colorectal cancer and some other cancers
What's analyzed:Blood
How used: To keep track of how well cancer treatments are working and check if cancer has come back or spread

CD19

Cancer types:B-cell lymphomas and leukemias
What's analyzed:Blood and bone marrow
How used:To help in diagnosis and to help determine treatment

CD20

Cancer type:Non-Hodgkin lymphoma
What's analyzed:Blood
How used: To help determine treatment

CD22

Cancer types:B-cell lymphomas and leukemias
What's analyzed: Blood and bone marrow
How used:To help in diagnosis and to help determine treatment

CD25

Cancer type:Non-Hodgkin (T-cell) lymphoma
What's analyzed: Blood
How used:To help determine treatment

CD30

Cancer types:Classic Hodgkin lymphoma, B-cell and T-cell lymphomas
What's analyzed:Tumor
How used:To help determine treatment

CD33

Cancer type:Acute myeloid leukemia
What's analyzed:Blood
How used:To help determine treatment

Chromogranin A (CgA)

Cancer type: Neuroendocrine tumors
What's analyzed:Blood
How used: To help in diagnosis, assessment of treatment response, and evaluation of recurrence

Chromosome 17p deletion

Cancer type: Chronic lymphocytic leukemia
What's analyzed: Blood
How used:To help determine treatment

Chromosomes 3, 7, 17, and 9p21

Cancer type:Bladder cancer
What's analyzed:Urine
How used:To help in monitoring for tumor recurrence

Circulating tumor cells of epithelial origin (CELLSEARCH)

Cancer types:Metastatic breast, prostate, and colorectal cancers
What's analyzed: Blood
How used:To inform clinical decision making, and to assess prognosis

Cytokeratin fragment 21-1

Cancer type:Lung cancer
What's analyzed:Blood
How used:To help in monitoring for recurrence

Cyclin D1 (CCND1) gene rearrangement or expression

Cancer types:Lymphoma, myeloma
What’s analyzed:Tumor
How used:To help in diagnosis

Des-gamma-carboxy prothrombin (DCP)

Cancer type:Hepatocellular carcinoma
What's analyzed:Blood
How used:To monitor the effectiveness of treatment and to detect recurrence

DPD gene mutation

Cancer types:Breast, colorectal, gastric, and pancreatic cancers
What's analyzed: Blood
How used: To predict the risk of a toxic reaction to 5-fluorouracil therapy

EGFR gene mutation

Cancer type:Non-small cell lung cancer
What's analyzed:Tumor
How used: To help determine treatment and prognosis

Estrogen receptor (ER)/progesterone receptor (PR)

Cancer type:Breast cancer
What's analyzed:Tumor
How used: To help determine treatment

FGFR2 and FGFR3 gene mutations

Cancer type: Bladder cancer
What's analyzed:Tumor
How used:To help determine treatment

Fibrin/fibrinogen

Cancer type:Bladder cancer
What's analyzed:Urine
How used:To monitor progression and response to treatment

FLT3 gene mutations

Cancer type:Acute myeloid leukemia
What's analyzed:Blood
How used: To help determine treatment

Gastrin

Cancer type:Gastrin-producing tumor (gastrinoma)
What's analyzed:Blood
How used:To help in diagnosis, to monitor the effectiveness of treatment, and to detect recurrence

HE4

Cancer type: Ovarian cancer
What's analyzed: Blood
How used:To plan cancer treatment, assess disease progression, and monitor for recurrence

HER2/neu gene amplification or protein overexpression

Cancer types:Breast, ovarian, bladder, pancreatic, and stomach cancers
What's analyzed:Tumor
How used:To help determine treatment

5-HIAA

Cancer type:Carcinoid tumors
What's analyzed:Urine
How used:To help in diagnosis and to monitor disease

IDH1 and IDH2 gene mutations

Cancer type:Acute myeloid leukemia
What's analyzed:Bone marrow and blood
How used:To help determine treatment

Immunoglobulins

Cancer types:Multiple myeloma and Waldenström macroglobulinemia
What's analyzed: Blood and urine
How used:To help diagnose disease, assess response to treatment, and look for recurrence

IRF4 gene rearrangement

Cancer types:Lymphoma
What’s analyzed:Tumor
How used:To help in diagnosis

JAK2 gene mutation

Cancer type:Certain types of leukemia
What's analyzed:Blood and bone marrow
How used:To help in diagnosis

KRAS gene mutation

Cancer types:Colorectal cancer and non-small cell lung cancer
What's analyzed: Tumor
How used:To help determine treatment

Lactate dehydrogenase

Cancer types:Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma
What's analyzed:Blood
How used:To assess stage, prognosis, and response to treatment

Microsatellite instability (MSI) and/or mismatch repair deficient (dMMR)

Cancer types: Colorectal cancer and other solid tumors
What's analyzed: Tumor
How used: To guide treatment and to identify those at high risk of certain cancer-predisposing syndromes

MYC gene expression

Cancer types:Lymphomas, leukemias
What’s analyzed:Tumor
How used:To help in diagnosis and to help determine treatment

MYD88 gene mutation

Cancer types:Lymphoma, Waldenström macroglobulinemia
What’s analyzed: Tumor
How used:To help in diagnosis and to help determine treatment

Myeloperoxidase (MPO)

Cancer type: Leukemia
What’s analyzed: Blood
How used:To help in diagnosis

Neuron-specific enolase (NSE)

Cancer types: Small cell lung cancer and neuroblastoma
What's analyzed:Blood
How used: To help in diagnosis and to assess response to treatment

NTRK gene fusion

Cancer type:Any solid tumor
What’s analyzed:Tumor
How used:To help determine treatment

Nuclear matrix protein 22

Cancer type: Bladder cancer
What's analyzed: Urine
How used:To monitor response to treatment

PCA3 mRNA

Cancer type: Prostate cancer
What's analyzed:Urine (collected after digital rectal exam)
How used:To determine need for repeat biopsy after negative biopsy

PML/RARα fusion gene

Cancer type: Acute promyelocytic leukemia (APL)
What's analyzed: Blood and bone marrow
How used:To diagnose APL, to predict response to all-trans-retinoic acid or arsenic trioxide therapy, to assess effectiveness of therapy, to monitor minimal residual disease, and to predict early relapse

Prostatic Acid Phosphatase (PAP)

Cancer type:Metastatic prostate cancer
What's analyzed:Blood
How used: To help in diagnosing poorly differentiated carcinomas

Programmed death ligand 1 (PD-L1)

Cancer types: Non-small cell lung cancer, liver cancer, stomach cancer, gastroesophageal junction cancer, classical Hodgkin lymphoma, and other aggressive lymphoma subtypes
What's analyzed:Tumor
How used: To help determine treatment

Prostate-specific antigen (PSA)

Cancer type: Prostate cancer
What's analyzed:Blood
How used: To help in diagnosis, to assess response to treatment, and to look for recurrence

ROS1 gene rearrangement

Cancer type: Non-small cell lung cancer
What's analyzed:Tumor
How used:To help determine treatment

Soluble mesothelin-related peptides (SMRP)

Cancer type:Mesothelioma
What's analyzed:Blood
How used: To monitor progression or recurrence

Somatostatin receptor

Cancer type:Neuroendocrine tumors affecting the pancreas or gastrointestinal tract (GEP-NETs)
What's analyzed:Tumor (by diagnostic imaging)
How used:To help determine treatment

T-cell receptor gene rearrangement

Cancer type:T-cell lymphoma
What's analyzed:Bone marrow, tissue, body fluid, blood
How used: To help in diagnosis; sometimes to detect and evaluate residual disease

Terminal transferase (TdT)

Cancer types: Leukemia, lymphoma
What’s analyzed: Tumor, blood
How used:To help in diagnosis

Thiopurine S-methyltransferase (TPMT) enzyme activity or TPMT genetic test

Cancer type:Acute lymphoblastic leukemia
What's analyzed: Blood and buccal (cheek) swab
How used: To predict the risk of severe bone marrow toxicity (myelosuppression) with thiopurine treatment

Thyroglobulin

Cancer type:Thyroid cancer
What's analyzed:Blood
How used:To evaluate response to treatment and to look for recurrence

UGT1A1*28 variant homozygosity

Cancer type:Colorectal cancer
What's analyzed: Blood and buccal (cheek) swab
How used:To predict toxicity from irinotecan therapy

Urine catecholamines: VMA and HVA

Cancer type: Neuroblastoma
What's analyzed:Urine
How used:To help in diagnosis

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1)

Cancer type:Breast cancer
What's analyzed:Tumor
How used:To determine aggressiveness of cancer and guide treatment

FoundationOne CDx (F1CDx) genomic test

Cancer type:Any solid tumor
What's analyzed: Tumor, blood
How used: As a companion diagnostic test to determine treatment

Guardant360 CDx genomic test

Cancer type: Any solid tumor
What’s analyzed: Blood
How used: As a companion diagnostic test to determine treatment and for general tumor mutation profiling

5-Protein signature (OVA1)

Cancer type:Ovarian cancer
What's analyzed:Blood
How used:To pre-operatively assess pelvic mass for suspected ovarian cancer

17-Gene signature (Oncotype DX GPS test)

Cancer type:Prostate cancer
What's analyzed:Tumor
How used:To predict the aggressiveness of prostate cancer and to help manage treatment

21-Gene signature (Oncotype DX)

Cancer type:Breast cancer
What's analyzed: Tumor
How used:To evaluate risk of distant recurrence and to help plan treatment

46-Gene signature (Prolaris)

Cancer type:Prostate cancer
What's analyzed:Tumor
How used:To predict the aggressiveness of prostate cancer and to help manage treatment

70-Gene signature (Mammaprint)

Cancer type:Breast cancer
What's analyzed: Tumor
How used:To evaluate risk of recurrence