Hereditary breast–ovarian cancer syndromes (HBOC) are

cancer syndrome A hereditary cancer syndrome (familial/family cancer syndrome, inherited cancer syndrome, cancer predisposition syndrome, cancer syndrome, etc.) is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affec ...

s that produce higher than normal levels of

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

and additional cancers in genetically related

families Family (from ) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). It forms the basis for social order. Ideally, families offer predictability, structure, and safety as ...

(either one individual had both, or several individuals in the pedigree had one or the other disease). It accounts for 90% of the hereditary cancers. The hereditary factors may be proven or suspected to cause the pattern of breast and ovarian cancer occurrences in the family. The name HBOC may be misleading because it implies that this genetic susceptibility to cancer is mainly in women. In reality, both sexes have the same rates of gene mutations and HBOC can predispose to other cancers including prostate cancer and pancreatic cancer. For this reason, the term "King syndrome" has recently come into use. The new name references Mary-Claire King who identified the genes ''BRCA1'' and ''BRCA2''. Most hereditary breast-ovarian cancer syndromes are inherited in an autosomal dominant pattern. Biallelic and homozygous inheritance of defective alleles that confer this syndrome is usually an embryonically lethal condition; live cases usually experience a severe form of

Fanconi anemia Fanconi anemia (FA) is a rare, autosomal recessive genetic disease characterized by aplastic anemia, congenital defects, endocrinological abnormalities, and an increased incidence of developing cancer. The study of Fanconi anemia has improve ...

Causes

BRCA1 and BRCA2 mutations and absolute cancer risk

A number of

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s are associated with HBOC. The most common of the known causes of HBOC are: *

BRCA mutation A ''BRCA'' mutation is a mutation in either of the ''BRCA1'' and ''BRCA2'' genes, which are tumour suppressor genes. Hundreds of different types of mutations in these genes have been identified, some of which have been determined to be harmful, ...

s: Harmful mutations in the ''

BRCA1 Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the ''BRCA1'' () gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. ''BRCA1'' is a ...

'' and ''

BRCA2 ''BRCA2'' and BRCA2 () are human genes and their protein products, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associate ...

'' genes can produce very high rates of breast and ovarian cancer, as well as increased rates of other cancers. Mutations in ''BRCA1'' are associated with a 39-46% risk of ovarian cancer and mutations in ''BRCA2'' are associated with a 10-27% risk of ovarian cancer. Other identified genes include: * ''

MLH1 DNA mismatch repair protein Mlh1 or MutL protein homolog 1 is a protein that in humans is encoded by the ''MLH1'' gene located on chromosome 3. The gene is commonly associated with hereditary nonpolyposis colorectal cancer. Orthologs of human ...

'', ''

MSH2 DNA mismatch repair protein Msh2 also known as MutS homolog 2 or MSH2 is a protein that in humans is encoded by the ''MSH2'' gene, which is located on chromosome 2. MSH2 is a tumor suppressor gene and more specifically a caretaker gene that codes ...

'', '' MSH6'', '' PMS2'': mutations in genes that lead to

Lynch Syndrome Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary predisposition to colon cancer. HNPCC includes (and was once synonymous with) Lynch syndrome, an autosomal dominant genetic condition that is associated with a high risk of colon ...

put individuals at risk for ovarian cancer. * ''

TP53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

'': Mutations cause Li-Fraumeni syndrome. It produces particularly high rates of breast cancer among younger women with mutated genes, and despite being rare, 4% of women with breast cancer under age 30 have a mutation in this gene. * '' PTEN'': Mutations cause Cowden syndrome, which produces

hamartoma A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended fr ...

s (benign polyps) in the colon, skin growths, and other

clinical sign Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

s, as well as an increased risk for many cancers. * '' CDH1'': Mutations are associated with lobular breast cancer and

gastric cancer Stomach cancer, also known as gastric cancer, is a malignant tumor of the stomach. It is a cancer that develops in the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes ...

. * ''

STK11 Serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the ''STK11'' gene. Expression Testosterone and DHT treatment of murine 3T3-L1 or hum ...

'': Mutations produce

Peutz–Jeghers syndrome Peutz–Jeghers syndrome (often abbreviated PJS) is an dominance (genetics), autosomal dominant genetic disorder characterized by the development of benign hamartomatous Polyp (medicine), polyps in the human gastrointestinal tract, gastrointestinal ...

. It is extremely rare, and creates a predisposition to breast cancer, intestinal cancer, and

pancreatic cancer Pancreatic cancer arises when cell (biology), cells in the pancreas, a glandular organ behind the stomach, begin to multiply out of control and form a Neoplasm, mass. These cancerous cells have the malignant, ability to invade other parts of ...

. * ''

CHEK2 CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. Mutations to the CHEK2 gene have been link ...

'': Approximately one out of 40 northern Europeans have a mutation in this gene, making it a common mutation. It is also one of the most frequently mutated genes after BRCA among Hispanics in the United States. Considered a moderate-risk mutation, it may double or triple the carrier's

lifetime risk In epidemiology, incidence reflects the number of new cases of a given medical condition in a population within a specified period of time. Incidence proportion Incidence proportion (IP), also known as cumulative incidence, is defined as the p ...

of breast cancer, and also increase the risk of

colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...

and

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

. * '' ATM'': Mutations cause ataxia telangectasia; female carriers have approximately double the normal risk of developing breast cancer. * ''

PALB2 Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the ''PALB2'' gene. Function This gene encodes a protein that functions in genome maintenance (DNA repair#Double-strand breaks, double ...

'': Studies vary in their estimate of the risk from mutations in this gene and the frequency of mutations in this gene may be different among different populations. It may be moderate risk, or as high as ''BRCA2''. For many of these genes, inheriting both defective alleles usually result in an embryonically lethal phenotype. Live cases suffer from a severe form of

Fanconi Anemia Fanconi anemia (FA) is a rare, autosomal recessive genetic disease characterized by aplastic anemia, congenital defects, endocrinological abnormalities, and an increased incidence of developing cancer. The study of Fanconi anemia has improve ...

; biallelic mutations of BRCA1 lead to Fanconi anemia complementation group S, and biallelic mutations of BRCA2 lead to complementation group D1. Approximately 45% of HBOC cases involve unidentified genes, or multiple genes.

Diagnosis

Prevention

People with ''BRCA1'' and ''BRCA2'' mutations are recommended to have a

transvaginal ultrasound Vaginal ultrasonography is a medical ultrasonography that applies an ultrasound transducer (or "probe") in the vagina to visualize organs within the pelvic cavity. It is also called transvaginal ultrasonography because the ultrasound waves go ''a ...

1-2 times per year. Screening with

CA-125 Mucin-16 (MUC-16) also known as Ovarian cancer-related tumor marker CA125 is a protein that in humans is encoded by the ''MUC16'' gene. MUC-16 is a member of the mucin family glycoproteins. MUC-16 has found application as a tumor marker or biom ...

is also recommended. Prophylactic

salpingo-oophorectomy In medicine, salpingo-oophorectomy is the removal of an ovary and its fallopian tube. This procedure is most frequently associated with prophylactic surgery in response to the discovery of a BRCA mutation, particularly those of the normally tumo ...

(removal of the ovaries and

fallopian tubes The fallopian tubes, also known as uterine tubes, oviducts or salpinges (: salpinx), are paired tubular sex organs in the human female body that stretch from the ovaries to the uterus. The fallopian tubes are part of the female reproductive sy ...

to prevent cancer) is recommended at age 35-40 for people with ''BRCA1'' mutations and at age 40-45 for people with ''BRCA2'' mutations. An increasing number women who test positive for faulty BRCA1 or BRCA2 genes choose to have risk-reducing surgery. At the same time the average waiting time for undergoing the procedure is two-years which is much longer than recommended.

References

External links

{{DEFAULTSORT:Hereditary Breast-Ovarian Cancer Syndrome Ovarian cancer Breast cancer Hereditary cancers Rare cancers Syndromes affecting the breast Syndromes in females