Presentation on theme: "Genetic and Molecular Epidemiology"— Presentation transcript:
1 Genetic and Molecular Epidemiology Bio364Special Thanks toEmily Chen, Ph.D.Department Of Pharmacological Sciences
2 Lecture Breast Cancer Statistics Breast Cancer Subtypes & Potential Risk FactorsBreast Cancer Susceptibility GenesBreast Cancer Prognosis
3 2011 ESTIMATED US CANCER DEATHS * Cancer Statistics 2011, American Cancer Society
4 FEMALE BREAST CANCER INCIDENCE RATES FEMALE BREAST CANCER INCIDENCE RATES* BY RACE & ETHNICITY, US,*Rates are age-adjusted to the 2000 US standard populationData source: Surveillance, Epidemiology, and End Results (SEER) Program, , Division of Cancer Control and Population Science, National Cancer Institute, Data for whites and blacks are from the SEER 9 registries. Data for other race/ethnicities are from the SEER13 registries.
5 Lecture Breast Cancer Statistics Breast Cancer Subtypes & Potential Risk FactorsBreast Cancer Susceptibility GenesBreast Cancer Prognosis
6 PROGRESSION OF BREAST CANCER Histologic Subtypes By Percentage Of CasesInfiltrating ductal carcinoma (IDC): the most commonly diagnosed breast tumor; metastatic (lymphatics); account for 75% of breast cancersDuctal carcinoma in situ (DCIS): most common type of non-invasive breast cancerLobular carcinoma in situ (LCIS): 2.8 per 100,000 women; high incidence in women aged yearsInfiltrating lobular carcinoma (ILC): <15% of invasive breast cancersMedullary carcinoma: ~ 5% ; generally occurs in younger womenMucinous (colloid) carcinom: <5% of invasive breast cancer casesPapillary carcinoma: older women (>60 years); 1-2% of all breast cancersMetaplastic breast cancer: <1% ; older women (>60 years); higher incidence in African American Women
7 INTRINSIC SUBTYPES OF BREAST CANCER Basal-Like (Triple Negative, cytokeratin 5/6+ &/or EGFR+)Aggressive subtypeHigh grade histology, and high mitotic rateRisk at younger age (<40)More likely preenopausal African American WomenLuminal A(ER+ &/or PR+, HER-)Most common subtypeLess aggressiveLower histological gradeGood prognosisHormone responsiveAssociated with increasing ageHER2+ (ER-)Less common, highly aggressive subtypeHigh grade histologyRisk at young age (<40) greater than luminal subtypesAfrican American ethnicity maybe a risk factorOutcome improved with HER2Luminal B(ER+ &/or PR+, HER+)Similar to Luminal AMore frequently ER+/PR-Worse outcome than Luminal A
8 ESTABLISHED RISK FACTORS FOR BREAST CANCER Table Source: American Cancer Society. Breast Cancer Facts & Figures Atlanta.
9 ANATOMY OF A GENE DNA RNA PROMOTER Transcription Start site EXONS INTRONSPROMOTERRNATranslation start siteStop codon
10 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 genesPenetrance 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
11 FOR YOUR INFORMATION ONLY, THIS WILL NOT BE ON THE EXAM SUMMARY OF SIX BREAST CANCER SUSCEPTIBILITY GENESGenePop’n carrier frequencyRisk of BC by 70 yrs (95% CI)BRCA11 in 86065% (44-78%)BRCA21 in 74045% (31-56%)CHEK21 in 9011% (9-14%)ATM1 in 10023% (13-39%)TP531 in 5,00050-60% by 45 yrsPTEN1 in 250,00030-50%From Thompson & Easton J Mammary Gland Biol Neoplasia 9:221.
12 FOR YOUR INFORMATION ONLY, THIS WILL NOT BE ON THE EXAM BREAST CANCER METASTASIS – TISSUE TROPISM Cell 127, November 17, 2006