What you need to know about cancer

WHAT IS CANCER?

Cancer is an uncontrolled growth of abnormal cells, which, if not diagnosed and treated in a proper way, can lead to tissue damage, metastasis, and ultimately death.

The most common cancers in Russia, 2019

There are over 100 types of cancer. In Russia the most common cancers of them are:

13,1%
skin cancer
15%
skin cancer including melanoma
11,6%
breast cancer
9,6%
tracheal, bronchus, and lung cancer
7,1%
colon cancer
7,1%
prostate cancer
5,7%
stomach cancer
5%
rectal, rectosigmoid junction and anus cancer
4,8%
lymphoid and hematopoietic tissue cancer
4,2%
uterine body cancer
3,9%
kidney cancer
3,1%
pancreatic cancer
2,7%
cervical cancer
2,7%
bladder cancer
2,2%
ovarian cancer

The most common types of cancer

In males

16,3%
tracheal, bronchus, and lung cancer
15,7%
prostate cancer
10,6%
skin cancer
12,2%
melanoma

In females

21,2%
breast cancer
15,2%
skin cancer
17,2%
melanoma
7,8%
uterine body cancer
5%
cervical cancer

In children

45,3%
lymphoid and hematopoietic tissue cancer
15,5%
brain and other central nervous system cancers
6,3%%
kidney cancer

Symptoms

The typical symptoms of cancer will differ depending on the type and stage of the disease, but the most common include

  • fatigue,
  • weight loss,
  • pain,
  • skin changes,
  • seals,
  • disfunction of the internal organs,
  • unusual bleeding,
  • persistent cough,
  • fever, etc.

Risk factors

Heredity

The presence of breast, ovarian, colon, prostate, skin cancer cases among close relatives, etc.

Infections

H. pylori, Epstein-Barr virus, HPV, hepatitis B and C viruses

Environmental factors

Air pollution, exposure to ionizing radiation and UV rays, exposure to chemical or toxic substances, etc.

Lifestyle

Smoking, drinking alcohol, malnutrition, obesity, physical inactivity, etc.

Elderly age

9 out of 10 cancers are diagnosed in people aged 45 and older

5 out of 10 cancers occur in people over 70

Causes

For cancerogenesis the cell must accumulate several breakdowns (mutations) in its DNA as a result of errors in division. Normally, the immune system recognizes and kills cells that differ from normal, but disturbances in the functioning of this system (stress, old age, immunodeficiency, etc.) can lead to the development of a cancer.

In different types of tissues, mutations of different driver genes will lead to malignant cell transformation.
Moreover, in different people with the same type of tumor, the set of affected genes may differ.
The search for genetic triggers that led to malignant transformation of cells is the basis of the selection of targeted therapy and personalized medicine.

Formation of cancer

WHAT ARE THE DIFFERENT TYPES OF CANCER?

There are over 100 types of cancer

however, the NCI (National Cancer Institute) lists several general categories

Lymphoma and myeloma

cancer that initiates in the the immune system cells. Multiple myeloma (MM) and lymphoma are both types that affect cells in a human blood. MM is a cancer of the plasma cells while lymphoma is a cancer of the lymphocytes. There are T-cell lymphomas, B-cell lymphomas, Hodgkin’s lymphomas, non-Hodgkin’s lymphomas, and lymphoproliferative lymphomas.

Leukemia (Leukemia)

cancer that starts in blood-forming tissue, such as the bone marrow, and causes large numbers of abnormal blood cells to form and circulate. There are lymphoblastic leukemias (ALL and CLL), myelogenous leukemias (AML and CML), T-cell leukemia and hairy cell leukemia.

Carcinoma

cancer that starts in the cells that line organs: the skin, lungs, colon, pancreas, ovaries. There are epithelial, squamous and basal cell carcinomas, melanomas, papillomas and adenomas.

Sarcoma

cancer that starts in bones, cartilage, adipose tissue, muscle, blood vessels, or other connective or supportive tissues — "bone, soft tissue cancer". Osteosarcoma, synovial sarcoma, liposarcoma, angiosarcoma, rhabdosarcoma and fibrosarcoma.

Сentral nervous system cancer

cancer that starts in tissues of the brain and spinal cord—gliomas, meningiomas, pituitary adenomas, vestibular schwannomas, primary CNS lymphomas, and neuroectodermal tumors.

The types listed above do not include metastatic tumor cells.

The reason is metastatic cells usually originate from the cell type named above, but end up in tissue from which they did not originally develop. Therefore, if the term "metastatic cancer" is used, then for greater accuracy it should include the tissue from which the tumor arises.

For example, a patient may say about having or being diagnosed with "metastatic cancer", but a more accurate statement is "metastatic (breast, lung, colon, or other type) cancer that has spread to the organ in which it was detected"

Another example: a doctor describing a man whose cancer has spread to the bones would say that he has metastatic prostate cancer in the bone.

This is not "bone cancer", which would be cancer that started in the bone cells. Metastatic prostate cancer in the bone is treated in a different way than lung cancer in the bone.

Localizations

  • Head and neck
  • Esophagus
  • Kidneys
  • Prostate
  • Liver and bile ducts
  • Lungs
  • Stomach
  • Skin
  • Bladder
  • Female reproductive organs
    • Cervix
    • Endometrium
    • Ovaries / fallopian tubes
FORMS OF CANCER

Hereditary forms of cancer

Hereditary cancers are associated with genetic alterations that have arisen in germ cells or have been inherited and the presence of which causes an increased risk of malignant tumors.

For example, the association between a pathogenic genetic variant and cancer development is well-studied for the following genes:

BRCA1 and BRCA2
Breast and ovarian cancer (in women); prostate cancer (in men); pancreas cancer
MSH2 and MLH1
Colon cancer; ovarian and endometrial cancer (in women)
RB1
Retinoblastoma; osteosarcoma; lymphocytic leukemia; small cell lung cancer; mammary gland cancer; genital tumors
CDKN2A /p16
Melanoma; mesothelioma; glioblastoma
WT1
Nephroblastoma
VHL
CNS hemangioblastomas; kidney carcinomas
APC
Hepatocellular carcinoma, thyroid tumors, medulloblastomas, fibromas
PTEN
Mammary gland cancer; prostate cancer; ovarian cancer; endometrial cancer; thyroid cancer
ATM
T‑cell leukemia; B‑lymphoma; medulloblastoma; gliomas

A Brief Comparison of Molecular Methods in Oncology

Molecular genetic methods are primarily used in oncology for diagnosis clarification, disease prognosis, and for selection of the most effective therapy (including targeted cancer therapy)

Next-generation sequencing (NGS)

is the most advanced and promising method that allows performing whole genome, whole exome, and targeted sequencing. Sequencing multiple DNA fragments occurs in parallel, providing high information content at a relatively high speed. NGS can simultaneously assess the presence of various genetic abnormalities in DNA and RNA molecules, such as hotspot mutations (mutations with increased frequency in the population), single nucleotide variants (SNV), copy number variations (CNV), small insertions, deletions, and gene fusions.

Oncofocus is an excellent example of an NGS assay used in cancer laboratory diagnostics.

«Oncofocus is a targeted next-generation sequencing (NGS), a multi-biomarker assay based on the Ion Torrent platform that detects variants across 52 cancer-relevant genes.

1000
different variants are detected by Oncofocus test

Pros

  • A universal method that is able to detect a wide range of mutations
  • Allows to perform diagnostics without prior hypothesis
  • Multiple candidate genes can be analyzed simultaneously
  • Only requires 10 ng of DNA or RNA
  • One of the most sensitive methods

Cons

  • High cost
  • The method is used to diagnose only solid tumors

Other molecular genetic methods used in oncology

FISH — fluorescent in situ hybridization

FISH (fluorescent in situ hybridization) — allows you to determine the exact location of the nucleotide sequences on the DNA or RNA, visualizing them with complementary fluorescent DNA probes. FISH detects chromosomal rearrangements (deletions, duplications, translocations, inversions). In oncology, it is most applicable to clarify the diagnosis and to determine tumor status when selecting therapy.

Detects chromosomal aberrations: deletions, duplications, translocations, inversions

Pros

  • Fast results

Cons

  • Expedient to use when a mutation in a particular chromosome is suspected (cannot serve as a screening test)
  • Requires confirmation of tumor molecular profile by other methods
  • Unable to detect intra-chromosomal aberrations, i.e. most abberation types
  • False positive results are possible (1-5%)
  • High cost
  • Detects chromosomal aberrations: deletions, duplications, translocations, inversions

arrayCGH — comparative genomic hybridization on microarrays

arrayCGH (comparative genomic hybridization on microarrays) is a method that detects unbalanced chromosomal rearrangements (deletions and duplications) of the entire genome. During the analysis, test and control DNA are labeled with different fluorescent dyes, mixed and hybridized on microarrays with DNA probes, quantitatively comparing the intensity of fluorescence.

Pros

  • Allows to analyze the presence of pathogenic variants in the whole genome simultaneously

Cons

  • Indicates only the presence of a variant and requires additional methods for clarification
  • Unable to detect balanced chromosomal rearrangements and point nucleotide variants (replacements, deletions, insertions)
  • Demanding to the incoming DNA concentration
  • High cost

PCR — Polymerase Chain Reaction

PCR (polymerase chain reaction) is a simple and effective laboratory diagnostic method that allows multiple copies of specific DNA or RNA fragments to be multiplied for qualitative or quantitative assessment of the fragment sought. In oncology, it can be used to detect single-nucleotide genetic variants (allele-specific PCR) or microRNA. More often, however, PCR is part of more sophisticated diagnostic methods, such as sequencing. In addition, PCR is widely used to detect the presence of potentially carcinogenic pathogens (HPV types 16 and 18, EBV infections, HBV and HCV, retroviruses, etc.).

Detects the presence of potentially carcinogenic pathogens HPV types 16 and 18, EBV infection, HBV and HCV, retroviruses, etc.

Pros

  • Relatively inexpensive
  • Accessible
  • Enables detection of potentially carcinogenic viral and bacterial DNA/RNA agents
  • Allows use of any biomaterial containing DNA or RNA

Cons

  • False positive results may occur
  • In diagnostic laboratories the analysis is usually limited to searching for the most common mutations in a given population
  • For best performance, it must be combined with other methods

Treatment

In cases where a malignant tumor is not operable, the patient receives combined treatment:

Combination of

  • surgery,
  • chemotherapy,
  • radiotherapy,
  • immunotherapy or targeted therapy.

Meanwhile, immunotherapy and targeted drugs are the most effective and, at the same time, safe method for healthy tissues.

Their use is based on the search for molecular biological markers of diagnosed cancer for the subsequent preparation of an effective treatment plan.