Adenomatous Polyposis Coli (APC)
Located on chromosome 5; the APC gene is considered a "gatekeeper" gene, and the loss of APC is among the earliest events in the chromosomal instability (CIN) colorectal tumor pathway. The important role of APC in predisposition to colorectal tumors is supported by the association of APC germline mutations with familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP).

Adenomatous Polyposis Syndromes (APS)
A term that collectively refers to the hereditary cancer syndromes that involve adenomatous colon polyps: familial adenomatous polyposis (FAP), attenuated FAP, and MYH-associated polyposis (MAP).

Allele
One version of a gene at a given location (locus) along a chromosome.

Amsterdam Criteria
The research criteria for defining HNPCC families were established by the International Collaborative Group (ICG) meeting in Amsterdam in 1990.

1. One member diagnosed with colorectal cancer before age 50.
2. Two affected generations.
3. Three affected relatives, 1 of them a first-degree relative of the other 2.
4. Familial adenomatous polyposis should be excluded.
5. Tumors should be verified by pathological examination.

Amsterdam Criteria II

1. There should be at least 3 relatives with an HNPCC-associated cancer (colorectal cancer, cancer of the endometrium, small bowel, ureter, or renal pelvis).
2. One should be a first-degree relative of the other 2.
3. At least 2 successive generations should be affected.
4. At least 1 should be diagnosed before age 50.
5. Familial adenomatous polyposis should be excluded in the colorectal cancer cases.
6. Tumors should be verified by pathological examination.

Ashkenazi Jewish
The Eastern European Jewish population primarily from Germany, Poland, Lithuania, Ukraine and Russia, as opposed to the Sephardic Jewish population primarily from Spain, parts of France, Italy, and North Africa. The majority of Jewish individuals in the United States are of Ashkenazi descent.

Attenuated Familial Adenomatous Polyposis
Attenuated FAP (AFAP) is characterized by a significant risk for colon cancer, but fewer colonic adenomatous polyps (average of 30) than seen in classic FAP. Polyps tend to be found more proximally in the colon than in classic FAP. The average age of colon cancer diagnosis in individuals with AFAP is age 50-55 years, which is 10-15 years later than that observed in classic FAP, but younger than that of individuals in the general population with sporadically occurring colon cancer. The American Gastroenterological Association recommends genetic testing once an individual reaches 20 or more cumulative polyps however AFAP has been diagnosed in patients with fewer than 20 polyps.

Autosomal Dominant
A pattern of Mendelian inheritance whereby an affected individual possesses one copy of a mutant allele and one normal allele. (In contrast, recessive diseases require that the individual have two copies of the mutant allele.) Individuals with autosomal dominant diseases have a 50-50 chance of passing the mutant allele and hence the disorder onto their children.

Autosomal Recessive
Describes a trait or disorder requiring the presence of two copies of a gene mutation at a particular locus in order to express observable phenotype; specifically refers to genes on one of the 22 pairs of autosomes (non-sex chromosomes).

Biallelic
A term used when referring to both copies of one gene (i.e. one inherited from the mother and one from the father).

Biallelic Damage
Damage to both maternal and paternal copies of a gene.

BRCA1
A tumor suppressor gene located on chromosome 17. When mutated the BRCA1 (BR for Breast, CA for Cancer) gene is one of the genes responsible for hereditary breast and ovarian cancer.

BRCA2
A tumor suppressor gene located on chromosome 13. When mutated the BRCA2 (BR for Breast, CA for Cancer) gene is one of the genes responsible for hereditary breast and ovarian cancer.

Chemoprevention
The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer.

Chromosomes
One of the threadlike "packages" of genes and other DNA in the nucleus of a cell. Different kinds of organisms have different numbers of chromosomes. Humans have 23 pairs of chromosomes, 46 in all: 44 autosomes and two sex chromosomes. Each parent contributes one chromosome to each pair, so children get half of their chromosomes from their mothers and half from their fathers.

Colectomy
The surgical removal of the colon. A total colectomy is the surgical removal of the colon and rectum. A subtotal colectomy is the surgical removal of the colon or portions of the colon only (not the rectum).

Colonoscopy
An examination of the inside of the colon using a thin, lighted tube (called a colonoscope) inserted into the rectum. If abnormal areas are seen, tissue can be removed and examined under a microscope to determine whether disease is present.

Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE)
CHRPE are discrete, flat, pigmented lesions of the retina that do not cause clinical problems. It is thought that CHRPE are present at birth. Observation of multiple or bilateral CHRPE may be an indication that an at-risk family member has inherited FAP, whereas isolated or unilateral lesions may be seen in the general population. Visualization of CHRPE may require examination of the ocular fundus with an indirect ophthalmoscope through a dilated pupil.

De novo Mutation
An alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents or in the fertilized egg itself. De novo mutations seen in FAP/AFAP have a 1 in 2 chance of being passed onto the carrier's offspring. Approximately 20%-30% of FAP mutations are considered de novo.

Deoxyribonucleic Acid (DNA)
DNA is a molecule that makes up chromosomes. It is composed of four units (called bases) that are designated A, T, G, and C. The sequence of the bases spell out instructions for making all of the proteins in an organism. The instruction set for each individual protein is a gene. A change in one of the DNA letters making up a gene is a mutation. In some cases, these mutations can alter the protein instructions and lead to disease. Each individual passes their chromosomes on to their children, and therefore pass down the DNA instructions. It is these instructions that cause certain traits, such as eye or hair color, to be inherited.

Desmoid Tumors
Proliferative, locally invasive, nonmetastasizing, fibromatous tumors in a collagen matrix. Although they do not metastasize, they can grow very aggressively and be life threatening. Studies have found that 10% of FAP patients develop desmoids.

Disease-Causing Mutation
A permanent structural alteration in DNA. These alterations can cause or predispose an individual to a specific disease.

DNA Replication
The process by which the DNA double helix unwinds and makes an exact copy of itself.

DNA Sequencing
Determining the exact order of the base pairs in a segment of DNA.

Exon
The region of a gene that contains the code for producing the gene's protein. Each exon codes for a specific portion of the complete protein. In some species (including humans), a gene's exons are separated by long regions of DNA (called introns or sometimes "junk DNA") that have no apparent function.

Familial Adenomatous Polyposis (FAP)
A colon cancer predisposition syndrome in which hundreds to thousands of adenomatous colonic polyps develop, beginning at a mean age of 16 years (range 7-36 years). By age 35 years, 95% of individuals with FAP have polyps. Without colectomy, colon cancer is inevitable. The mean age of colon cancer in untreated individuals is 39 years (range 34-43 years). Extracolonic manifestations are variably present and include polyps of the gastric fundus and duodenum, osteomas, dental anomalies, congenital hypertrophy of the retina pigment epithelium (CHRPE), soft tissue tumors, desmoid tumors, and associated cancers.

First degree relative
A relative who is a person's biological mother, father, full sibling, or child. Step parents, step children, or half siblings are not first degree relatives.

Flexible Sigmoidoscopy
An internal examination of the rectum and distal sigmoid colon using a type of small camera (flexible sigmoidoscope). Approximately 40%-50% of the colon is visualized during a flexible sigmoidoscopy.

Gene
The basic unit of heredity, consisting of a segment of DNA arranged in a linear manner along a chromosome. A gene codes for a specific protein or segment of protein leading to a particular characteristic or function.

Genetic Code
The instructions in a gene that tell the cell how to make a specific protein. A, T, G, and C are the "letters" of the DNA code; they stand for the chemicals adenine, thymine, guanine, and cytosine, respectively, that make up the nucleotide bases of DNA. Each gene's code combines the four chemicals in various ways to spell out 3-letter "words" that specify which amino acid is needed at every step in making a protein.

Genetic Counseling
A short-term educational counseling process for individuals and families who have a genetic disease or who are at risk for such a disease. Genetic counseling provides patients with information about their condition and helps them make informed decisions.

Genetic Discrimination
Unique treatment of an individual or members of that individual's family solely because of real or perceived differences from the ‘normal’ genome of that individual.

Genome
The entire DNA contained in an organism or a cell, which includes both the chromosomes within the nucleus and the DNA in mitochondria.

Hereditary
Transmission from parent to child of information contained in the genes.

Hereditary Mutation
A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation.

Hereditary Nonpolyposis Colon Cancer (HNPCC)
An inherited disorder in which affected individuals have a higher-than-normal chance of developing colorectal cancer and certain other types of cancer, often before the age of 50. Also called Lynch syndrome.

HNPCC-Related Cancers
Other primary cancers included in HNPCC are cancers of the endometrium, ovary, stomach, ureter/renal pelvis, brain, biliary tract, pancreas, small bowel, and sebaceous adenomas. The risk of these cancers in individuals with HNPCC is elevated above that of the general public.

Informed Consent
Permission given by an individual to proceed with a specific test or procedure, with an understanding of the risks, benefits, limitations, and potential implications of the procedure itself and its results.

Inherited
Transmission of a trait through genes from parents to offspring.

Metachronous
Multiple separate occurrences, such as multiple primary cancers developing at intervals.

Microsatellite Instability (MSI)
The presence of a discrepancy between the sizes of microsatellites in DNA from tumor tissue compared to non-tumor tissue from the same person, often resulting from mutations in a gene in the DNA mismatch repair pathway (MMR) that would normally correct these errors.

Microsatellites
Repetitive segments of DNA two to five nucleotides in length (dinucleotide/trinucleotide/tetranucleotide/pentanucleotid e repeats), scattered throughout the genome in non-coding regions between genes or within genes (introns). These regions are inherently unstable and susceptible to mutations.

Mismatch Repair Mechanism (MMR)
The DNA 'proof-reading' system controlled by certain genes that identifies, excises, and corrects errors in the pairing of the bases during DNA replication. Mutations in the genes responsible for this mechanism can lead to certain genetic diseases and some forms of cancer.

MLH1
Located on chromosome 3p21, the primary function of the MLH1 (mutL homolog 1) gene is mismatch repair during DNA replication. When mutated, the MLH1 gene is one of the genes responsible for hereditary nonpolyposis colorectal cancer.

MSH2
Located on chromosome 2p16, the primary function of the MSH2 (mutS homolog 2) gene is mismatch repair during DNA replication. When mutated, the MSH2 gene is one of the genes responsible for hereditary nonpolyposis colorectal cancer.

MSH6
Located on chromosome 2p16, the primary function of MSH6 (mutL homolog 6) gene is mismatch repair during DNA replication. When mutated, the MSH6 gene is one of the genes responsible for hereditary nonpolyposis colorectal cancer.

Mutation
A permanent structural alteration in DNA. In most cases, DNA changes either have no effect or may be disease-causing.

MYH
Located on chromosome 1p34, the primary function of MYH (mutY homolog) gene is base excision repair. When biallelic mutations are present, the MYH gene is associated with polyposis.

MYH-Associated Polyposis (MAP)
An inherited condition resulting in the formation of multiple adenomatous polyps in the colon. MAP has been diagnosed in patients with very few polyps, as well as those with closer to 1000 polyps.

Osteomas
Bony growths found most commonly on the skull and mandible; however, they may occur in any bone of the body and can be associated with FAP. Osteomas do not usually cause clinical problems and do not become malignant. Osteomas may appear in children with FAP prior to the development of colonic polyps.

p16
A tumor suppressor gene that regulates cellular proliferation and growth by acting as a cyclin-dependent kinase 4 (CDK4) inhibitor. The p16 gene is located on chromosome 9p21.

Pedigree
A graphic representation of a family tree, often showing a particular disease state.

Polymorphism
(synonym: polymorphism allele) Natural variations in a gene, DNA sequence, or chromosome that have no adverse effects on the individual and occur with fairly high frequency in the general population.

Pre-Symptomatic
The stage prior to an individual presenting with symptoms that are clinically relevant to the disease in question.

Prophylactic Bilateral Mastectomy
The removal of breast tissue prior to the detection of disease. Both subcutaneous mastectomy and simple (total) mastectomy have been used for prophylaxis. Only 90% to 95% of breast tissue is removed with subcutaneous mastectomy. In a total or simple mastectomy, removal of the nipple-areolar complex increases the proportion of breast tissue removed compared to subcutaneous mastectomy. However, some breast tissue is usually left behind with both procedures.

Prophylactic Bilateral Oophorectomy
Surgical removal of the ovaries prior to the detection of disease.

Selective Estrogen Receptor Modulator (SERM)
A drug that acts like estrogen on some tissues but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs.

Sequence Analysis
Process by which the nucleotide sequence is determined for a segment of DNA.

Serum CA-125
A blood test that measures the level of CA-125, a substance found in blood, other body fluids and some tissues. Increased levels of CA-125 may be a sign of ovarian cancer.

Siblings
Brothers and/ or sisters of an individual.

Sporadic Cancer
Cancer occurring in individuals without a family history of cancer or in individuals who do not carry a high-risk mutation.

Synchronous
Multiple primary cancers occurring simultaneously.

Transvaginal (Endovaginal) Ultrasound
High-resolution images of the uterus and ovaries; may be used to screen for endometrial or ovarian cancer.

Tumor Suppressor Gene
A protective gene that normally limits the growth of tumors. When a tumor suppressor gene is mutated, it may fail to keep a cancer from growing. BRCA1 and BRCA2 are tumor suppressor genes.

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