Lecture 12 Smoking and Cancer Did you know 32 251 Americans died due to firearm injuries in 2011 55 000 American soldiers died in the Vietnam War 292 000 American soldiers died in World War 2 2 976 people died in the WTC Pentagon on 9 11 158 040 Americans will die of lung cancer this year Cigarettes kill more Americans than alcohol car accidents suicide AIDS homicide illegal drugs combined Nearly 1 of every 5 deaths is related to smoking Each year a staggering 440 000 people die in the US of tobacco use Tobacco Facts Tobacco products are the only legal consumer products that can be LETHAL when used exactly as the manufacturer intends In 2014 lung and bronchus cancer killed more people than pancreas breast and colorectal cancer Warning There is no safe tobacco product The use of any tobacco product including cigarettes cigars pipes and spit tobacco metholated low tar naturally grown or additive free can cause cancer and other adverse health effects Smoking and Cancer Risk Estimated new cases and deaths from lung cancer non small cell and small cell combined in the U S in 2015 New cases 221 200 Deaths 158 040 Lung cancer risk increases with cigarette consumption Types of Lung Cancer Non Small Cell Carcinoma 85 includes squamous adenocarcinoma and large cell carcinoma Of these adenocarcinoma has superseded squamous as the most common type If detected early these may be treated surgically Lung Carcinoid Tumor 5 Grow very slowly and rarely spread Small Cell Carcinoma 15 Characterized by rapid growth and dissemination Treated with chemotherapy and radiation therapy Non Small Cell Lung Cancer NSCL Adenocarcinoma usually develops on the outer boundaries of the lungs and is more commonly found in women than in men Cause of 40 of lung cancers in US Non Small Cell Lung Cancers Squamous Cell Carcinoma Commonly starts in the bronchi and may not spread as rapidly as other lung cancers 30 Large Cell Carcinoma Is ant lung tumor that cannot be classified Cause of 15 of all lung cancer in UA Lung Cancer Lung cancer starts in the lungs as a growth of abnormal cells and often metastasizes spreading to other organs in the body It is the leading cause of cancer related deaths Here are the main risk factors types detection methods and treatments Lung cancer most commonly spreads to brain lymph nodes lymphatic system adrenal glands liver and bones Common risk factors for lung cancer may include a cumulative combination of exposure to tobacco smoke asbestos radon or other pollutants Small Cell Lung Cancer 13 of cases Stages Limited Stage Only occurs in one lung Extensive Stage Has metastasized outside lung tissue or in distant organs Non Small Cell Lung Cancer 87 of cases Spreads slowly Stages Occult Cancer cells in sputum but no tumors in lung Stage 0 Cancer cells in innermost lining of lung Stages 1A 1B Tumor is isolated in the lung or cancer has spread to the lung s main airways or inner lining Stage 2A 2B Cancer has spread to nearby lymph nodes chest wall diaphragm membrane around the heart lining between the lungs or the main airway Stages 3A AB Cancer has spread to additional lymph nodes further spread to chest wall diaphragm membrane around the heart lining between the lungs or and main airway It may have spread to the aorta heart trachea sternum or esophagus for the first time or lung may have collapsed or become inflamed 4A 4B Malignant growths in more than one lobe of one lung in both lungs or cancers has spread to other organs Small Cell Carcinoma of the Lung Smoking tobacco is the major risk factor for developing small cell lung cancer Also called oat cell carcinoma can create its own hormones which alter body chemistry Without treatment small cell carcinoma of the lung has the most aggressive clinical course of any type of pulmonary tumor with median survival from diagnosis of only 2 to 4 months Has greater tendency to be widely disseminated by the time of diagnosis but is much more responsive to chemotherapy and irradiation Tobacco smoke Cancer How How Tobacco smoke is made up of more than 7 000 chemicals including over 70 known to cause cancer carcinogens Epigenetics methylations turns off genes acting together in some way Carcinogens binds directly to DNA Chromosomal instability P53 90 of SCLC RB 90 of SCLC too rare in NSCLA alteration chromosome 3 90 and 70 SCLC and NSCLC RAS family oncogenes The Smoking Gun Linking Cigarettes to Cancer 1 Burning tars in cigarettes create the chemical benzo pyrene which is absorbed by lung tissue suppressing gene P53 2 Within the cell s nucleus bp is modified to BPDE and binds to the tumor 3 BPDE causes mutations at three specific hot spots on the P53 gene resulting in unrestricted cell division cancer Within a lung cell benzopyrene is converted to an epoxide The epoxide reacts readily with guanine G positions of the DNA helix If not corrected by the cell s DNA repair mechanism this guanine addict is misread as a thymine by the DNA polymerase that copies chromosomes during replication Ultimately the original G C base pair may be replaced by a T A base pair a mutation called a transversion Cultured cells treated with benzopyrene shows the same spectrum of G T transversions as found in the k ras and p53 gene of smokers These mutational hot spots map well to the guanine binding sites of benzopyrene expoxide Benzopyrene can produce the major known activing mutation in the 12th codon of the K ras gene an oncogene Mutations of p53 and K ras in Lung Cancer P53 Guardian of the genome tumors The highest rate for any cancer A tumor suppressor gene it acts like brakes on cell division it prevents the cell cycle from progressing If DNA damage or mutations are present Mutations in p53 gene are found in 70 of lung P53 acts as a checkpoint into the critical synthesis S Mitosis M Phase After receiving information from DNA repair systems p53 can signal the cell to stop dividing allowing time for a mutation to be repaired before it is passed on to daughter cells The K ras gene codes a tumor activator K ras acts like a gas pedal on cell division The K ras protein resides on the inner side of the cell membrane where it shuttles growth signals from cell surface to the nucleus K ras An Oncogene Mutation in K ras gene result in a K ras protein that is essentially stuck in an on position perpetuating a signaling cascade in the absence of any real signal from a growth factor Facts about Addiction to Nicotine Nicotine is the tobacco plant s natural protection from being eaten
View Full Document
Unlocking...