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Genetic and Molecular Epidemiology. Bio364 Special Thanks to Emily Chen, Ph.D. Department Of Pharmacological Sciences. Lecture . Breast Cancer Statistics Breast Cancer Subtypes & Potential Risk Factors Breast Cancer Susceptibility Genes Breast Cancer Prognosis. - PowerPoint PPT Presentation
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Genetic and Molecular Epidemiology
Bio364
Special Thanks to Emily Chen, Ph.D.
Department Of Pharmacological Sciences
Lecture • Breast Cancer Statistics • Breast Cancer Subtypes & Potential Risk
Factors• Breast Cancer Susceptibility Genes• Breast Cancer Prognosis
2011 ESTIMATED US CANCER DEATHS
* Cancer Statistics 2011, American Cancer Society
FEMALE BREAST CANCER INCIDENCE RATES* BY RACE & ETHNICITY, US, 1975-2007
*Rates are age-adjusted to the 2000 US standard populationData source: Surveillance, Epidemiology, and End Results (SEER) Program, 1975-2007, Division of Cancer Control and Population Science, National Cancer Institute, 2011. Data for whites and blacks are from the SEER 9 registries. Data for other race/ethnicities are from the SEER13 registries.
Lecture • Breast Cancer Statistics • Breast Cancer Subtypes & Potential Risk
Factors• Breast Cancer Susceptibility Genes• Breast Cancer Prognosis
PROGRESSION OF BREAST CANCER
Histologic Subtypes By Percentage Of Cases1. Infiltrating ductal carcinoma (IDC): the most commonly diagnosed breast tumor;
metastatic (lymphatics); account for 75% of breast cancers 2. Ductal carcinoma in situ (DCIS): most common type of
non-invasive breast cancer3. Lobular carcinoma in situ (LCIS): 2.8 per 100,000
women; high incidence in women aged 40-50 years 4. Infiltrating lobular carcinoma (ILC): <15% of
invasive breast cancers5. Medullary carcinoma: ~ 5% ; generally occurs in
younger women6. Mucinous (colloid) carcinom: <5% of invasive breast
cancer cases7. Papillary carcinoma: older women (>60 years); 1-2% of
all breast cancers8. Metaplastic breast cancer: <1% ; older women (>60
years); higher incidence in African American Women
INTRINSIC SUBTYPES OF BREAST CANCER
HER2+ (ER-)• Less common, highly
aggressive subtype• High grade histology• Risk at young age (<40)
greater than luminal subtypes
• African American ethnicity maybe a risk factor
• Outcome improved with HER2
Basal-Like (Triple Negative, cytokeratin 5/6+ &/or EGFR+)• Aggressive subtype• High grade histology, and
high mitotic rate• Risk at younger age (<40)• More likely preenopausal
African American Women
Luminal B(ER+ &/or PR+, HER+)• Similar to Luminal A• More frequently ER+/PR-• Worse outcome than
Luminal A
Luminal A(ER+ &/or PR+, HER-)• Most common subtype• Less aggressive• Lower histological grade• Good prognosis• Hormone responsive• Associated with increasing
age
ESTABLISHED RISK FACTORS FOR BREAST CANCER
Table Source: American Cancer Society. Breast Cancer Facts & Figures 2009-2010. Atlanta.
ANATOMY OF A GENE
DNA
Transcription Start site
EXONSINTRONS
PROMOTER
RNA
Translation start site
Stop codon
GENETIC LINKS TO BREAST CANCER
Epidemiologic studies have clearly established the role of family history as an important risk factor for both breast and ovarian cancer.
The search for genes associated with hereditary susceptibility to breast cancer has been facilitated by studies of large kindreds with multiple affected individuals, and has led to the identification of several susceptibility genes
Penetrance of Mutations - Estimates of penetrance by age 70 years for BRCA1 and BRCA2 mutations show a large range, from 40% to 87% for breast cancer
FOR YOUR INFORMATION ONLY, THIS WILL NOT BE ON THE EXAM
SUMMARY OF SIX BREAST CANCER SUSCEPTIBILITY GENES
GenePop’n carrier frequency Risk of BC by 70 yrs (95%
CI)
BRCA1 1 in 860 65% (44-78%)BRCA2 1 in 740 45% (31-56%)CHEK2 1 in 90 11% (9-14%)ATM 1 in 100 23% (13-39%)TP53 1 in 5,000 50-60% by 45 yrsPTEN 1 in 250,000 30-50%
From Thompson & Easton. 2004. J Mammary Gland Biol Neoplasia 9:221.
FOR YOUR INFORMATION ONLY, THIS WILL NOT BE ON THE EXAM
BREAST CANCER METASTASIS – TISSUE TROPISM
Cell 127, November 17, 2006