Breast cancer (Breast cancer) - Genes ATM, BARD1, BRCA1, BRCA2, BRIP1, CASP8, CDH1, CHEK2, CTLA4, CYP19A1, FGFR2, H19, LSP1, MAP3K1, MRE11A, NBN, PALB2, PTEN, RAD51, RAD51C, STK11 , TERT, TOX3, TP53, XRCC2 and XRCC3.

Breast cancer is a disease in which certain cells of the breast become abnormal and multiply uncontrollably to form a tumor. Although breast cancer is much more common in women, this cancer can also develop in men. The most common form of breast cancer starts in the cells lining the milk ducts (ductal cancer). Other forms of breast cancer starts in the milk - producing glands (lobular cancer) or other parts of the breast. Most men have little or no lobular tissue, lobular cancer in men is rare.

In its early stages, breast cancer is painless or obvious manifestation of symptoms. As the cancer progresses, the signs and symptoms may include a lump or thickening in or near the breast, a change in the size or shape of the breast, nipple discharge, pain or retraction, skin irritation, dimpling or peeling. However, these changes can occur as part of many different disorders. Having one or more of these symptoms does not mean that a person has breast cancer. In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If breast cancer spreads, cancer cells appear more frequently in the bones, liver, lungs or brain. A small percentage of all breast cancers are grouped into families. Inherited cancers are associated with inherited genetic mutations. The hereditary breast cancers tend to occur prior to sporadic cases and are more likely to involve both breasts.

Some breast cancers are grouped into families are associated with inherited mutations in certain particular genes, such as BRCA1 (breast cancer 1) gene or BRCA2 (breast cancer 2) gene. These genes are described as "high penetrance" because they are associated with a high risk of developing breast, ovarian cancer, and several other cancers in women who have mutations. Males with mutations in these genes also have an increased risk of various cancers, including breast cancer. The proteins encoded from the BRCA1 and BRCA2 genes are involved in DNA binding damaged, which helps to maintain the stability of the genetic information of a cell. These genes are described as tumor suppressors as they help to control the cells grow and divide too fast or uncontrolled.

A significantly increased risk of breast cancer is also a feature of several rare genetic syndromes. These include Cowden syndrome, which is often due to mutations in PTEN (phosphatase and tensin homolog); Hereditary diffuse gastric cancer due to mutations in CDH1 (Cadherin 1); the Li-Fraumeni syndrome, which usually develops as a result of mutations in the TP53 (tumor protein p53); and Peutz-Jeghers syndrome, often due to mutations in STK11 (Serine / threonine kinase 11). The encoded proteins from these genes act as tumor suppressors. Mutations in any of these genes may allow cells to grow and divide unchecked, leading to the development of a cancerous tumor. Like BRCA1 and BRCA2 genes, these genes are considered "high penetrance" because mutations greatly increase the likelihood of developing cancer in people. In addition to breast cancer, mutations in these genes increase the risk of several other cancers during the life of a person.

Mutations in other genes dozen been studied as possible risk factors for breast cancer. These genes are described as "low penetrance" or "moderate penetrance" because the changes in each of these genes appear to contribute less to the total risk of breast cancer. This genes include: (ATM serine / threonine kinase, 11q22-q23), BARD1 (BRCA1 associated RING domain 1, 2q35), BRIP1 (BRCA1 interacting protein C-terminal helicase 1, 17q22.2), CASP8 (caspase 8 2q33 -q34), CHEK2 (checkpoint kinase 2, 22q12.1), CTLA4 (cytotoxic T-lymphocyte associated protein 4, 2q33), CYP19A1 (cytochrome P450 family subfamily A member 19 1, 15q21.1), FGFR2 (fibroblast growth factor receptor 2, 10q26), H19 (H19, imprinted maternally Expressed transcript, 11p15.5), LSP1 (lymphocyte-specific protein 1, 11p15.5), MAP3K1 (mitogen-activated protein kinase kinase kinase 1, 5q11.2), MRE11A ( MRE11 homolog A, double strand break repair nuclease, 11q21), NBN (Nibrin, 8q21), PALB2 (partner and localizer of BRCA2, 16p12.2), RAD51 (RAD51 recombinase, 15q15.1), RAD51C (RAD51 paralog C, 17q22 ), TERT (telomerase reverse transcriptase, 5p15.33), TOX3 (TOX high mobility group box family member 3, 16q12.1), XRCC2 ( X-ray repair complementing defective repair in Chinese hamster cells 2, 7q36.1) and XRCC3 (X-ray repair complementing defective repair in Chinese hamster cells 3, 14q32.3). Some of these genes encode the synthesis of proteins that interact with proteins encoded from genes BRCA1 or BRCA2. Others act through different pathways. It is believed that the combined influence of variations in these genes can significantly affect the risk of developing breast cancer.

In many families, genetic changes associated with hereditary breast cancer are unknown. Identifying additional genetic risk factors for breast cancer is an active area of medical research. In addition to genetic changes they have been identified many personal and environmental factors that contribute to the risk of developing breast cancer. These factors include gender, age, ethnicity, prior history of breast cancer, changes in breast tissue, and hormonal and reproductive factors. A history of breast cancer in closely related members of the family is also an important risk factor, especially if the cancer occurred in early adulthood.

The BRCA1 (breast cancer 1) gene, located on the long arm of chromosome 17 (17q21), it belongs to a class of genes called tumor suppressor genes. This gene encodes a protein involved directly in the repair of damaged DNA. At the core of many types of normal cells, the BRCA1 protein interacts with other proteins, including proteins encoded from the genes RAD51 and BARD1, to repair DNA breaks. The BRCA1 protein plays a role in maintaining the stability of the genetic information of a cell. Probably the BRCA1 protein also regulates the activity of other genes and plays a critical role in embryonic development. To perform these functions, the protein interacts with many other proteins, including tumor suppressors and other proteins that regulate cell division. They have identified more than 1,000 mutations in the BRCA1 gene associated with increased risk of breast cancer in women. Most of these mutations lead to encoding an abnormally short version of the BRCA1 protein or prevent encoding any protein from a gene copy. Other mutations change amino acids in the protein or remove large segments of DNA of the BRCA1 gene. It is likely that a defective BRCA1 protein is unable to assist in the repair of damaged DNA or correct mutations that occur in other genes. As these defects accumulate, they may allow cells to grow and divide without control and form a tumor.

BRCA2 (breast cancer 2) gene, located on the long arm of chromosome 13 (13q12.3), belongs to a class of genes called tumor suppressor genes. This gene encodes a protein that is directly involved in the repair of damaged DNA. At the core of many cell types, the BRCA2 protein interacts with other proteins, including proteins encoded from the genes RAD51 and PALB2, to repair DNA breaks. By contributing in DNA repair, the BRCA2 protein plays a role in maintaining the stability of the genetic information of a cell. BRCA2 is likely that the protein may have additional functions within cells. For example, the protein can help regulate cytokinesis. They have identified more than 800 mutations in the BRCA2 gene, many of which are associated with an increased risk of breast cancer. Some mutations inserted or deleted nucleotides in the gene. Most of these genetic changes interrupt the protein coding from a copy of the gene in each cell, which results in an abnormally small, non - functional version of the BRCA2 protein. It is likely that the defective protein is unable to assist in the repair of damaged DNA or correct mutations that occur in other genes. As these defects accumulate, they may allow cells to grow and divide without control and form a tumor.

CDH1 (Cadherin 1), located on the long arm of chromosome 16 (16q22.1), encodes a protein called epithelial cadherin or E-cadherin. This protein lies within the membrane surrounding epithelial cells. E-cadherin belongs to a family of proteins called cadherins whose function is to help cell adhesion to form organized tissue. In addition to its role in cell adhesion, E-cadherin is involved in the transmission of chemical signals within cells, control of cell maturation and cell movement, and regulation of the activity of certain genes. E-cadherin also acts as a tumor suppressor protein. Inherited mutations of CDH1 increase the risk of lobular breast cancer. Studies have shown that often somatic mutations in the CDH1 gene occur in cases of lobular breast cancer in women with no family history of the disease. Some of these genetic changes occur within the gene itself, while others inactivate a region near the DNA that controls gene activity. It is likely that loss of E-cadherin can allow cells to grow and divide uncontrollably. Lack of this protein, which is essential for cell adhesion, can also make it easier for cancer cells shed from a primary tumor and spread to other parts of the body.

STK11 (Serine / threonine kinase 11), located on the short arm of chromosome 19 (19p13.3), encoding a tumor suppressor enzyme called serine / threonine kinase 11. In addition to its role in regulating cell division, this enzyme helps certain cell types to its polarization. It also contributes to the determination of the amount of energy you use a cell. This kinase also promotes apoptosis. Through a combination of these mechanisms, the serine / threonine kinase 11 helps preventing tumors, especially in the gastrointestinal tract, pancreas, cervix, ovaries and breast. The serine / threonine kinase 11 is required for normal development before birth. Changes in the STK11 gene increase the risk of developing breast cancer. These mutations represent inherited only a small fraction of all cases of breast cancer.

TP53 (tumor protein p53), located on the short arm of chromosome 17 (17p13.1), encodes a protein called p53. This protein acts as a tumor suppressor. The p53 protein is found in the nuclei of cells throughout the body, where it binds directly to DNA. When DNA in a cell is damaged, this protein plays a critical role in determining whether the DNA will be repaired or damaged cell undergoes apoptosis. If DNA can be repaired, p53 activates other genes to repair the damage. If the DNA can not be repaired, this protein prevents the cell from dividing and induces apoptosis. Heritable changes in TP53 greatly increase the risk of developing breast cancer as part of a syndrome rare cancer called the Li-Fraumeni syndrome. It is believed that these inherited mutations represent less than 1% of all cases of breast cancer. Many of these mutations change amino acids in the protein p53, which results in a nonfunctional version of this protein. Defective protein accumulates in the cells and can not regulate growth and cell division. In some cases of breast cancer, a copy of the TP53 gene is lost and the remaining copy has a mutation that prevents the cell encode any protein p53. Without this protein, DNA cells divide in an uncontrolled manner, leading to a cancerous tumor. Mutations in the TP53 gene are associated with larger tumors and more advanced than breast cancers TP53 mutations without disease.

Most cases of breast cancer are not inherited. These cancers are associated with genetic changes that occur only in cells of breast cancer and occur during the life of a person. In hereditary breast cancer, how the risk of cancer is inherited it depends on the implicated gene. For example, mutations in the BRCA1 and BRCA2 genes are inherited in an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to increase the chances of developing cancer. In other cases, inheritance risk of breast cancer is unclear. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer.

Tests performed in IVAMI: in IVAMI perform the detection of mutations associated with breast cancer, using the complete PCR amplification of the exons of the BRCA1, BRCA2, CDH1, STK11 and TP53 genes, or many others who have linked ( see in the text), respectively, and subsequent sequencing. We recommend starting the study by the BRCA1 and BRCA2 are responsible for most cases of breast cancer genes. For the H19 gene that is not transcribed, we would analyze the sequence of 2,000 bp for genetic alterations.

Samples recommended: for tests to determine the predisposition to the development of breast cancer, blood is recommended extracted with EDTA for separating blood leukocytes, or impregnated card sample dried blood (IVAMI may mail the card to deposit the sample blood). In the case of cancer it has developed, sending biopsy is recommended if it were a non - hereditary somatic mutation.