Familial Cancer Syndromes Overview
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Questions and Answers

What is the lifetime risk percentage for women who inherit a mutation in BRCA1?

  • 50%
  • 70%
  • 30%
  • >60% (correct)

    • What is the percentage reduction in breast cancer risk provided by risk-reducing bilateral mastectomy for BRCA1 and BRCA2 carriers?

  • >90% (correct)
  • 70%
  • 50%
  • 40%

    • Which of the following is NOT a common tumor suppressor gene associated with breast cancer?

  • TP53
  • RET (correct)
  • PTEN
  • CHEK2

    • How much does risk of developing melanoma increase when a first-degree relative is affected before 50 years of age?

    <p>6.5 times</p> Signup and view all the answers

    What is the role of BRCA1 and BRCA2 in cellular function?

    <p>Participating in DNA repair</p> Signup and view all the answers

    What percentage of melanoma cases are attributed to inherited familial forms?

    <p>5-10%</p> Signup and view all the answers

    What procedure is recommended for children who inherit a disease-causing mutation related to medullary thyroid carcinomas?

    <p>Thyroidectomy before the age of 6</p> Signup and view all the answers

    What is the function of the CDKN2A gene in relation to familial melanoma?

    <p>Tumor suppressor gene</p> Signup and view all the answers

    What is the primary function of tumor suppressor genes?

    <p>To inhibit cellular proliferation</p> Signup and view all the answers

    Which genetic alteration is required for oncogenes to promote tumorigenesis?

    <p>Gain-of-function mutations</p> Signup and view all the answers

    In the two-hit model of carcinogenesis, which scenario describes inherited retinoblastoma?

    <p>An affected individual often has an affected parent</p> Signup and view all the answers

    What distinguishes somatic mutations from germline mutations in cancer development?

    <p>Somatic mutations are not transmitted to offspring</p> Signup and view all the answers

    Which of the following is NOT typically associated with oncogenes?

    <p>Deletions of genetic material</p> Signup and view all the answers

    The TP53 gene is commonly mutated in what percentage of colorectal tumors?

    <p>40%</p> Signup and view all the answers

    What is the main difference in the occurrence of germline mutations for tumor suppressor genes compared to oncogenes?

    <p>Tumor suppressor genes commonly exhibit germline mutations leading to inherited syndromes</p> Signup and view all the answers

    Which cancer type is specifically highlighted as being associated with mutations in the TP53 gene?

    <p>Lung tumors</p> Signup and view all the answers

    What is the primary genetic requirement for inherited retinoblastoma?

    <p>Two mutations in the retinoblastoma gene</p> Signup and view all the answers

    What is the incidence rate of retinoblastoma in children?

    <p>1 in 20,000</p> Signup and view all the answers

    Which chromosome contains the RB1 gene associated with retinoblastoma?

    <p>Chromosome 13</p> Signup and view all the answers

    What is the survival rate for patients with retinoblastoma after 5 years?

    <p>95%</p> Signup and view all the answers

    What type of cancer are familial retinoblastoma patients particularly susceptible to later in life?

    <p>Soft tissue sarcomas</p> Signup and view all the answers

    In sporadic cases of retinoblastoma, how do the mutations occur?

    <p>Both mutations occur somatically.</p> Signup and view all the answers

    Which syndrome is characterized by early-onset tumors and is autosomal dominant?

    <p>Li-Fraumeni syndrome</p> Signup and view all the answers

    Which of the following is NOT a type of cancer associated with Li-Fraumeni syndrome?

    <p>Blastoma</p> Signup and view all the answers

    What is the percentage of individuals with an abnormal TP53 gene that develop invasive cancer by 70 years of age?

    <blockquote> <p>90%</p> </blockquote> Signup and view all the answers

    Which gene is primarily responsible for Familial Adenomatous Polyposis (FAP)?

    <p>APC</p> Signup and view all the answers

    What is the lifetime colorectal cancer risk for heterozygotes in Hereditary Nonpolyposis Colon Cancer (HNPCC)?

    <p>70-90%</p> Signup and view all the answers

    What percentage of HNPCC cases are caused by mutations in the MSH2 gene?

    <p>40-60%</p> Signup and view all the answers

    Which preventative measure is recommended starting at age 12 for individuals at risk of Familial Adenomatous Polyposis?

    <p>Annual colonoscopy</p> Signup and view all the answers

    What is the role of the MUTYH gene in relation to FAP?

    <p>It encodes a DNA repair protein.</p> Signup and view all the answers

    Which of the following statements about BRCA1 and BRCA2 is correct?

    <p>1-3% of all breast cancers are due to inherited mutations.</p> Signup and view all the answers

    Which type of cancer risk is associated with BRCA2 mutations in males?

    <p>Prostate cancer</p> Signup and view all the answers

    Study Notes

    Familial Cancer Syndromes

    • Familial cancer syndromes are a group of inherited disorders that can increase the risk of developing various cancers.
    • Cancer is a group of diseases characterized by uncontrolled cell growth.
    • Neoplasm is a mass of cells, or tumor, genetic and environmental factors contribute to their development.
    • Tumorigenesis is the formation of a tumor.
    • Malignant tumors invade nearby tissues and spread through metastasis.
    • Benign tumors do not invade nearby tissues or spread.
    • Cancer development involves signals, differentiation, growth, and cell division, and cell death (apoptosis).

    Cancer Causes: Genetics

    • Cancer genes can be somatic or germline.
    • Somatic cells are not inherited.
    • Germline cells are inherited and can be associated with cancer families.

    Classification of Cancer Genes

    • Tumor suppressor genes normally inhibit cellular proliferation, preventing uncontrolled cell growth.
    • Oncogenes activate proliferation, driving uncontrolled cell growth.
    • DNA repair genes fix damaged DNA, preventing mutations and cancer development..

    Oncogenes

    • Oncogenes originate from proto-oncogenes, which are involved in normal cell growth.
    • Proto-oncogenes become oncogenes through mutations.
    • Oncogenes lead to unregulated cell growth and differentiation, contributing to cancer.
    • Growth factors, growth factor receptors, signal transduction molecules, and nuclear transcription factors are involved.

    Oncogenes & TSG

    • A single mutated oncogene often suffices to trigger tumor progression.
    • Tumor suppressor genes are functionally disabled by mutations like deletions or loss-of-function mutations.
    • oncogenes are activated by mutations like gain-of-function mutations or gene amplification.

    Tumor Suppressor Genes

    • RB1, NF1, and TP53 are examples of tumor suppressor genes.

    TP53 Gene

    • Tumor protein p53 is a crucial gene, often mutated in various cancers.
    • p53 somatic mutations are found in more than 50% of human tumors, and in 70% of colorectal tumors, 40% of breast tumors and 60% of lung tumors.

    Two-Hit Model of Carcinogenesis

    • Knudson's two-hit model explains how inherited and sporadic retinoblastoma develop.
    • Inherited retinoblastoma involves an inherited germline mutation plus a somatic mutation.
    • Sporadic retinoblastoma requires two somatic mutations.

    Retinoblastoma

    • Retinoblastoma is the most prevalent childhood eye tumor (1/20,000 children.)
    • Symptoms typically appear before age 5.
    • 60% of retinoblastoma cases are due to somatic mutations, not inherited, 40% are inherited.
    • The RB1 gene is located on chromosome 13 and mutations can lead to tumors.
    • Patients with inherited retinoblastoma often have multifocal or bilateral tumors.
    • A white reflex (leukocoria) is a possible symptom.
    • 5-year survival rate is nearly 95%.
    • Patients with familial retinoblastoma may be prone to various cancers later.

    Li-Fraumeni Syndrome (LFS)

    • Autosomal dominant disorder, increasing predisposition to numerous cancers.
    • Cancers typically develop at an early age.
    • Multiple types of tumors may occur.
    • TP53 gene mutations are common in LFS.
    • Another tumor suppressor gene, CHEK2, is also associated with LFS.

    Familial Adenomatous Polyposis (FAP)

    • FAP is a rare, inherited syndrome characterized by numerous polyps in the colon.
    • Polyps typically manifest during the second decade of life.
    • Almost all (virtually 100%) with a positive family history who develop FAP will eventually develop colon cancer
    • risk doubles if a first degree relative is affected
    • APC is localized to 5q and is a tumor suppressor gene.
    • Mutations in APC are identified in FAP affected individuals. One third of FAP cases involve new APC mutations.
    • MUTYH encodes a DNA repair protein, and is associated with FAP in 10-20% of cases.

    Prevention of Familial Cancers

    • Regular screenings, like colonoscopies beginning at a young age, are crucial.
    • Nonsteroidal anti-inflammatory drugs (NSAIDs) may help reduce polyp size in some cases.

    Additional Cancers Associated with Known Syndromes

    • Syndromes like FAP and HNPCC increase the risk of other cancers like gastric, ovarian, and others to differing degrees.

    Treatments for Familial Cancers

    • Early detection is key to successful treatment, using molecular techniques to identify mutations.
    • Removal of adenomatous polyps may significantly decrease future risk.
    • Surgical resection, chemotherapy, and other treatments are often employed.

    Colon Cancer

    • APC gene mutations are present in 85% of sporadic colon cancers and are among the earliest alterations in colon cancer.
    • KRAS gene mutations are commonly seen 50% of colon tumors
    • TP53 gene mutations are seen in over 50% and occur later.
    • SMAD4 gene mutations, a tumor suppressor gene, are involved in colon cancers.

    Hereditary Nonpolyposis Colon Cancer (HNPCC)

    • Lynch syndrome is another colon cancer syndrome.
    • This is a different hereditary colon cancer syndrome from FAP (familial adenomatous polyposis)
    • It's autosomal dominant with high penetrance and a lifetime colorectal cancer risk up to 70-90%.
    • HNPCC is caused by mutations in genes like MSH2 and MLH1, crucial for DNA mismatch repair. (PMS2 and MSH6 are also involved)
    • Endometrial and ovarian cancers are also increased risks with HNPCC. The risk of endometrial cancer is 50% and ovarian cancer is 5-10% in patients with HNPCC.

    Inherited Breast Cancer

    • BRCA1 and BRCA2 are major genes linked to inherited breast cancers.
    • Lifetime risk is higher (1/8 to 1/12) when first degree relative is affected.
    • BRCA mutations (1-3%) significantly increase risk for women, and to a lesser degree men developing breast cancer.
    • Early-onset and bilateral breast cancers are more strongly associated with inherited mutations.
    • BRCA2 mutations also increase the risk of ovarian cancer (10 to 20% lifetime prevalence)

    Risk-Reducing Procedures

    • Oophorectomy reduces ovarian cancer risk by 90% and breast cancer risk slightly (50%) in some carriers.
    • Bilateral mastectomy drastically reduces breast cancer risk (up to 90%) in BRCA carriers.

    Familial Melanoma

    • Melanoma risk increases with family history suggesting genetic involvement.
    • A first-degree familial melanoma relative increases risk by twofold and significantly more if the melanoma is diagnosed before 50 years of age.
    • CDKN2A gene mutations are implicated in 10 to 40% cases of familial melanoma.

    Other Inherited Cancers

    • Various other inherited cancer syndromes, like neurofibromatosis type 2, Von Hippel-Lindau syndrome, Beckwith-Wiedemann syndrome, and others, are also recognized.

    Chromosome Instability Syndromes

    • These are a group of autosomal recessive disorders characterized by increased incidence of chromosome breaks.
    • Diseases like Ataxia-telangiectasia, Bloom syndrome, Fanconi anemia, and Xeroderma pigmentosum are included, with an increased risk for different types of cancers.
    • Certain alkylating agents (DEB, MMC) can increase the frequency of breaks in Fanconi Anemia.

    Liquid Biopsy

    • Liquid biopsies analyze blood for cancer cells (ctDNA) circulating in the blood.
    • Used to detect cancers early, monitor treatment efficacy, and identify recurrence.

    RET

    • RET is a proto-oncogene which can lead to inherited cancer syndromes, specifically affecting thyroid cancers.
    • Patients with sporadic medullary thyroid carcinoma's are advised to undergo RET gene testing.
    • ~ 1 to 7 % are found to have germline RET mutations, indicating a familial component, not sporadic.
    • prophylactic thyroidectomy is often considered.

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    Familial Cancer Syndromes PDF

    Description

    This quiz explores familial cancer syndromes and their genetic causes. It covers essential concepts such as tumorigenesis, types of tumors, and the classification of cancer genes. Test your understanding of how genetics influence cancer risk and tumor development.

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