7/13/16 Flashcards
I = P X A X T
I= environmental impact; p=population; a=affluence; t=technology
Growth in environ. impact = growth in population x growth in affluence x growth in technology
What are the top 5 countries in population growth in 2050?
1) India
2) China
3) USA
4) Nigeria
5) Indonesia
1969-2013: Death rate per 100,000 has decreased by ____
42.9&
Heart disease: ___ reduction
75%
Cancer: ____ reduction
17.9% reduction
Rate for COPD has increased ___ percent
100.6%
Unintentional injuries: ___ reduction
39.8%
Factors that make environmental disease hard to identify
latency, multi-factorial etiology, disease non-specificity, individual characteristics (susceptibility), dose-response relations, and mixed exposure scenarios
Biomarkers
molecular, biochemical or cellular alterations that are measurable in biological media, such as human tissues, cells, or fluids
Molecular epidemiology
incorporation of biomarkers into analytic, epidemiologic research
Molecular mechanisms
basic biological, physiological, biochemical sequence of events at the molecular and cellular levels that characterize the progression from an initiating event through clinical disease
Why do we care about molecular mechanisms?
Risk assessment - risk factors, susceptibility factors
Risk management - interventions
How big is our microbiome?
10^14-10^15 bacteria in our gut
How many cells in 1 gram of tissue?
10^9 cells
How many cells in average person?
10^13-10^14 cells
Pathways that are corrupted in cancer
Sustaining proliferative signaling Evading growth suppressors Activating invasion and metastasis Enabling replicative immortality Inducing angiogenesis Resisting cell death
Historical perspective of Cancer
1713 - Ramazzini - noted nuns had higher breast cancer incidence than other women
1761 - Hill - tobacco snuff use and nasal passage cancer
1775 - Pott - scrotal cancer in chimney sweeps
1895 - Rehn - occupation exposure to aromatic amines and bladder cancer
1915 - Ichikawa - first experimentally induced cancer
Evidence suggesting environmental agents as causes of human cancers
- cancer rates within a population change over time
- global geographic variation in incidence of specific cancers
- large differences in tumor incidence in a single country
- migrant populations assume the cancer incidence of their new environment within 1-2 generations
- twins study, environmental and cancer
Biomarkers of dose to humans: internal dose
Direct measure of toxic chemicals or their metabolites in cells, tissues, or body fluids (integrates multiple portals of entry, fluctuating exposures, relates exposure to dose)
Examples of biomarkers of internal dose
exhaled breath - volatile organic chemicals (ethanol)
blood levels - styrene, lead, cadmium, arsenic
fat concentrations - PCBs, and PBBs, DDT & TCDD
metabolites in urine - aflatoxin, benzene, arsenic
mutagen in urine - chemotherapeutic drugs, carcinogens
hair sample - arsenic
blood carboxyhemoglobin - CO
blood methemoglobinemia - organic nitrates
DNA adducts
cellular DNA: e.g. benzo[a]pyrene-DNA adducts in peripheral lymphocytes of coke oven workers; cisplatinum-DNA adducts in WBC of chemotherapy patients
Protein adducts
hemoglobin: ethylene oxide, aromatic amines, tobacco-specific nitrosamines, cisplatinum
albumin: aflatoxin B1
Cancers linked to smoking
lung, oral cavity, pharynx, larynx, esophagus, pancreas, bladders, nasal cavity, stomach, liver, kidney, ureter, cervix, myeloid leukemia
Carcinogens in tobacco smoke
PAH, nitrosamines, aromatic amines, aldehyde, phenols, volatile hydrocarbons, nitro compounds
the major addictive substance in tobacco products, but not a carcinogen
nicotine, but when nicotine is nitrosated -> converted to very potent carcinogen (NNK-nicotine-derived nitrosamino ketone)
tobacco-specific nitrosamines NNK
- formed during curing and processing of tobacco
- most abundant strong carcinogen in unburned tobacco
- present in tobacco smoke (100-400ng per cig)
- Lung is the main target of NNK
- both inhalation and skin exposures cause lung tumors
- classified as IARC Group 1 carcinogen
Second leading cause of lung cancer globally
Radon
Epigenetics
Heritable changes in gene expression that are not due to any alteration in the DNA sequence
- best known epigenetic marker - DNA methylation
Epigenetics and human disease
Epigenetics is the study of inherited changes in phenotype or gene expression caused by mechanisms other than changes int he underlying DNA sequence
