Hereditary diffuse gastric cancer: updated clinical practice guidelines

abstract – A brief summary of a paper (research article, thesis, review, in-depth analysis of a particular subject, etc.) and is often used to help the reader quickly ascertain the paper’s purpose.

bilateral LBC – Independent cancers in both breasts. The cancer in one breast hasn’t spread from the other.

CDH1 gene – The human genome is made up of 20,000 genes, each encoding a different protein that carries out one or more of the jobs a cell needs to live and grow. CDH1 is one of those genes, and encodes a protein called E-cadherin. The role of E-cadherin is to hold cells together, helping to build tissues and organs.

cleft lip/palate – Openings or splits in the upper lip, the roof of the mouth (palate) or both. Cleft lip and cleft palate result when facial structures that are developing in an unborn baby don’t close completely.

diffuse gastric cancer (DGC) – Also known as signet ring cell adenocarcinoma or linitis plastica, DGC grows rapidly in the lining of the stomach wall. These aggressive cancer cells do not form a mass; rather they are diffused (scattered widely or thinly) in the lining of the stomach wall.

familial cancer – Cancer that occurs in families more often than would be expected by chance. These cancers often occur at an early age, and may indicate the presence of a gene mutation that increases the risk of cancer. They may also be a sign of shared environmental or lifestyle factors.

first-degree relative – The parents, siblings, or children of an individual.

germline mutation – A germline mutation is a genetic variant that is present in a body’s germ cells (reproductive cells: sperm or egg) that becomes incorporated into the DNA of every cell in the body of the offspring. Germline mutations can be passed on from a parent to their offspring at the time of conception. Understanding a somatic mutation may help in understanding differences between hereditary gene mutations and non-hereditary mutations. A somatic mutation can occur in any of the cells of the body (skin, breast, stomach, liver, muscle, etc.) except the germ cells (sperm and egg) and therefore are not passed on to offspring. An alteration in DNA occurs after conception. These alterations can (but do not always) cause cancer or other diseases. Sporadic cancers (i.e. non-hereditary) are caused by somatic mutations in a cell where the cancer starts.

histopathological – The area of pathology that deals with the structure of diseased or abnormal tissue. Pathology is the scientific study of disease and its causes, processes, development and consequences.

linkage analysis – A technique used to find genes associated with particular traits or illnesses. If two genes sit near each other in the genome, they will be ‘linked’. That is, if someone inherits one of the genes, it is highly likely they will inherit the other one too. Linkage analysis relies on a genetic map, which is a large collection of markers with known locations in the genome. In the analysis, researchers look for a marker which happens to always occur in people from a family with the trait or disease. If they find one, they know the trait or disease gene (a normal gene, but with a mutation in it that affects its function) is very close to that marker. Since the location of that marker is known, its a small additional step to then find the gene you are after.

lobular breast cancer (LBC) – Cancer that begins in the lobules (milk glands) of the breast.

mortality – Mortality is another term for death. A mortality rate is the number of deaths due to a disease divided by the total population.

multidisciplinary – Combining or involving more than one field of study or area of specialty.

pathogenic – Causing or capable of causing disease.

precursor lesion – A cluster of abnormal cells that have not yet become cancerous. In situ lesions are an example of a precursor lesion. This refers to cells that are abnormal looking but have not moved from their normal cellular location. Stage T1a is the earliest stage of cancer in which abnormal cells have begun to move into the stomach’s underlying layers. Stage 1a cancers are sometimes also called precursor lesions because they are very slow growing and do not readily invade into deeper layers.

prophylactic total gastrectomy (PGT) – Preventive complete surgical removal of the entire stomach.

sporadic – Appearing in scattered or isolated instances.

screening – Individuals having endoscopy who do not know their mutation status, or those who do not have a proven pathogenic CDH1 mutation undergo screening.

second-degree relative – The aunts, uncles, grandparents, grandchildren, nieces, nephews, or half-siblings of an individual.

signet ring cell carcinoma – Also known as Diffuse Gastric Cancer (DGC) an aggressive type of cancer cell usually found in glandular cells that line the stomach or other digestive organs. The cells resemble signet rings (a finger ring with a small seal) when examined under a microscope.

surveillance – Individuals having endoscopy who are mutation-positive undergo surveillance.

VUS (Variant of Uncertain Significance) mutation – A VUS is a germline mutation with unclear effect, meaning that it is unclear whether or not the DNA change actually increases disease risk.