Different degrees of tumor and different stages exist

Both ____ and ____ important in cancer ***

Internal factors that can cause cancer:

External factors that can cause cancer:

Most cases of cancer are ***

Fewer than 10% of all tumors result from a familial disposition ***

Not all cases, whether sporadic or familial, have a genetic cause ***

Mutations of proteins in classes I-IV (growth factors, growth factor receptors, signal-transduction proteins, transcription factors) generally give rise to ________ ***

Cell-cycle control proteins (VI) mainly act as ______________, and are generally recessive. ***

Mutations in _______ greatly increase the probability of mutations in other genes

________________ that activate growth factor receptors (Ia) can also induce cancer.

_____________ stop the natural process of programmed cell death and may allow damaged cells to continue dividing.

Group of genes that cause normal cells to become cancerous when they are mutated ***

encode proteins that function to stimulate cell division, inhibit cell differentiation, and halt cell death ***

Genes that are relevant for the regulation of growth, repair, and cell survival, with malignant transformation supported through (recessive) loss-of-function mutations on both copies of the gene ***

They typically include DNA repair genes that are responsible for detecting and repairing genetic damage within a cell. ***

constant growth signal

unchecked cell growth

Tumor progression is multi-step → becomes progressively invasive as you obtain more mutations ***

multi-step

Oncogenes develop from mutations that result in a ________ ***

Most familial cancer predisposition syndromes result from mutations in tumor suppressor genes in which ________ favors development of a tumor ***

dominant at the cellular level ***

recessive at the cellular level ***

Inactivating mutations in both alleles is needed

can also be duplicated or multiplied (amplification), resulting in increased gene copy numbers and thus more gene products in the cell

The products of these genes inhibit cellular growth, proliferation, or cell cycle progression

Ensure genetic stability, for example, through DNA repair

Cancer development involves___ successive mutations that affect the two alleles of a tumor suppressor gene. ***

After gender and age, a positive family history is the strongest known predictive risk factor for breast cancer

Two of these predisposition genes were discovered in 1990 and 1994 and have been designated ____ and ____

BRCA1 is located on chromosome

BRCA2 is located on chromosome

Both BRCA genes are _________ that code for proteins involved in ___________. ***

Familial breast cancer caused by mutations in BRCA1 and BRCA2 is transmitted in an autosomal ______

BRCA1 and BRCA2 genes are truly recessive, but phenotype acts autosomal dominant

BRCA1 mutations are associated with an approximately threefold increase in the risk for ________ but very rarely lead to male breast cancer. ***

Strong association between _____ mutations and male breast cancer, with carriers facing a cumulative risk of 7% by the age of 70 years

Tumorigenesis is based on the “two-hit hypothesis"

_______ mutations show less association with prostate cancer but have been linked (in both sexes) to tumors of the pancreas, larynx, esophagus, colon, stomach, and biliary tract, and to melanomas.

a reduction of genetic variation that happens when a small group of individuals starts a new population

Proto-oncogenes: Mostly _______ mutations that cause permanent activation or altered function of the gene product

may be offered to women of specific ethnic background. It includes mutations known to be at greater frequencies because of founder effects

includes full sequence analysis of BRCA1 and BRCA2 and testing for specific large genomic rearrangements of BRCA1

BRCA1/2 and multiple, other high-risk gene mutations

Ashkenazi individuals: _____ have BRCA1 or BRCA2 mutation

General population: _______ have BRCA1 or BRCA2 mutation

-Germline mutation on chromosome 17

-Caused by mutations in the E-cadherin gene CDH1

-Premenopausal breast cancer (avg. age of onset 36 years)

-Childhood sarcoma, Brain tumors, Leukemia, Adrenocortical carcinoma

-Multiple hamartomas

-Excess of breast cancer

-Gastrointestinal malignancies

-Endometrial cancer

-Benign or malignant thyroid disease

-Lifetime risk for breast cancer between 25%-50% (Onset early, Often bilateral)

-Mutations in STK11 (tumor suppressor)

-Autosomal dominant

-Increased risk of developing cancer (GI tract, cervix, ovary and breast)

Management options for by hereditary breast/ovarian cancer patients