cancer Flashcards
what is a tumour?
a swelling of a part of the body, generally without inflammation, caused by an abnormal growth of tissue, whether benign or malignant
Benign
Benign
Localized growths of tissue
malignant
Malignant
Abnormal cells growth
Structural and functional alterations
Invasion of nearby tissues
Migrate and colonize other organs via blood and lymph
Success of therapy and survival depend on extent and control of metastases
Cells require six characteristics to become fully malignant
Production of growth signals Lack of sensitivity to antigrowth signals Resistance towards apoptosis Immortalization Stimulation of blood vessel production Ability to invade and metastasize
cancer approaches
Approaches Epidemiological approach Study designs Exposures vs outcomes Distribution
Experimental approach
Identification of carcinogens via lab testing
Experimental animals, mostly rodents-long term
No universal criteria to translate this data to cancer risk in humans
Effects of chemical agents on end-points belonging to DNA damage, mutagenicity, chromosome testing- short term
Mechanical tests
Identification of intermediate steps in compound-specific carcinogenic process
Limitations
Non-genotoxic carcinogens such as hormones and obesity with no bio-markers
Classification of carcinogenic chemicals by the IARC (International Agency for Research on Cancer
Group: 1
Evidence of carcinogenicity in humans:
-Derived from epidemiological studies; sufficient
GROUP 2A
Evidence of carcinogenicity in humans :Limited; agent is experimental carcinogen
GROUP 2B
Evidence of carcinogenicity in humans: Experimental agent; inadequate or non-existent evidence
GROUP 3
Evidence of carcinogenicity in humans
:Non-classifiable as to its carcinogenicity in humans
Group 4
Evidence of carcinogenicity in humans:
Probably non-carcinogenic to humans
Risk factors leading to cancer
- Genetic predisposition (small percentage)
- Family
2.Tobacco smoking
Single major cause of human cancer globally- 30% of all cancers in HICs; less in LMICs because later start of tobacco epidemic
3.Behavioural
Diet and obesity
Exposure to aflatoxin( produced by fungi in tropical areas)
liver cancer
High intake of red meat and processed meat colorectal cancer
Alcohol
4.Viruses
5.Bacteria
6.Parasites
7.Occupation and pollution
8.Ionizing and non-ionizing radiation
-Acute lymphocytic leukemia
Acute and chronic myeloid leukemia
Cancers of breast, lung, bone, brain, thyroid
lung cancer histology
Histology Small cell carcinoma Non-small cell Squamous cell decreasing Adenocarcinoma increasing Large cell
Staging System?
way cancer is thought to
spread
Non-Small Cell Lung Cancer:
Staging
T = Main Tumor N = Regional Nodes M = Distant Metastasis
TNM Staging: Regional Lymph Nodes
NO
No tumor spread to regional lymph
nodes
N1
Spread detected in nodes close to
the tumor
N2
Spread found in nodes in middle of
chest
TNM Staging: Primary Tumor (T)
Based on Size of Tumor - bigger more chance
of breaking off and spreading
T1 < or equal 3 cm diameter
T2 >3 m diameter
TNM Staging: Distant Metastasis
MO No spread or metastasis outside
of chest
M1 Spread or metastasis present
outside of chest, for example in brain
or bone or liver
A etiology and risk factors of lung cancer
Tobacco smoke Increases risk by 20-40 fold, even for moderate smokers Cumulative risk of lung cancer is 16% Excess risk levels off in ex-smokers Exposure to involuntary smoking increases risk among non-smokers-20% excess risk compared to unexposed non-smokers Contribution of all aspects of smoking Average consumption Duration of smoking Time since quitting Age at start Type of tobacco product Inhalation pattern
Protective factor of lung cancer
Intake of cruciferous vegetables
High content of isothiocyanates
Ionizing radiation of lung cancer
Underground miners
Atomic bomb survivors
Radiotherapy for breast cancer or ankylosing spondylitis
Annual low dose CT scan among smokers
Lung cancer prevention
Prevention
Control tobacco smoking, including involuntary
Reduction in exposure to occupational an environmental carcinogens-indoor pollution and radon
Increase consumption of fruits and vegetables
Liver cancer risk factors
Risk factors and causes
Hep B and C
Main causes of hepatocellular carcinoma (HCC)-75% of liver cancers
Risk increases with early age at infection
Presence of liver cirrhosis is a pathogenic step
Risk factors and causes
Contamination of foodstuffs with aflatoxins especially B1( mycotoxins produced by fungi Aspergillus Flavus and parasiticus)
From improper storage of cereals, peanut’s, other vegetables
Alcoholic cirrhosis-VIP
In populations with low prevalence of HBV and HCV, and low exposure to aflatoxins
Tobacco smoking
Use of oral contraceptives
Diabetes/overweight/obesity
Development of non-alcoholic fatty liver disease (NAFLD)
Excess fat accumulation in liver
Ranges from isolated hepatic steatosis to non-alcoholic steatohepatitis (NASH)
NASH is aggressive and progresses to cirrhosis and HCC
Liver cancer prevention
Prevention
HBV vaccination in perinatal period
Aflatoxin reduction in foods
Limited by logistic and economic factors
Control of transmission for HCV
Medical treatment for carriers of HCV and HBV (interferons and newer antiviral drugs)
Control of tobacco smoking and alcohol drinking
Liver cancer screening
Fetal antigen α-fetoprotein secreted by HCC and not normal liver
No evidence of impact of screening such as decreased mortality at a population level
Stomach cancer risk factors
Risk factors Helicobacter pylori High prevalence in developing countries Precancerous stages Chronic and atrophic gastritis Not sufficient cause Interaction between virulence factors and immune subversion and manipulation mechanisms 5% of all cases Tobacco smoking 10% of all cases Salt and salted foods Strong environmental influence on disease More varied affluent diet Better food conservation-refrigeration Control of H.pylori
Protective factors for stomach cancer
Protective factors
Supplements with beta-carotene, vitamin E and selenium
Prevention of stomach cancer
Prevention Decreased consumption of cured meats and salt preserved foods Eradication of H.pylori Childhood Adolescence Mother-to-child transmission
Screening of Stomach cancer
Early detection in Japan by X-ray photofluorography to identify early lesions followed by gastroscopy
Histology of Colorectal cancer
Histology
Adenocarcinoma
Preceded by adenomatous polyp
General risk factors of Colorectal cancer
Risk factors
Carriers of one adenoma larger than 1 cm
Risk increases if multiple adenomas present
Prevalence of adenomas detected during colonoscopy parallels incidence of colon cancer
Alcohol consumption
Tobacco smoking
Ulcerative colitis and Crohn’s disease
Higher for young age at diagnosis and presence of dysplasia
Diabetes
Cholecystectomy
Women: cancers of endometrium, ovary, breast-due to shared hormonal or dietary factors
Cancer of the colon
Hereditary rare conditions
First degree relative of colon cancer patients
high intake of meat and smoked, salted, or processed foods
Colorectal cancer prevention
Primary prevention Increased physical activity Avoidance of overweight and obesity Reduce alcohol intake Quitting smoking No routine recommendation of aspirin
Secondary prevention
Removal of adenomas via flexible colonoscopy
Protective factor of Colorectal cancer
Vitamin D
Aspirin
NSAIDS
Hormone therapy in menopause and other female hormones (OC)
Surveillance of colorectal cancer
Surveillance Flexible colonoscopy for adenomas Faecal occult blood Detection of adenoma Low specificity To a lesser extent-low sensitivity Sigmoidoscopy for distal colon Current recommendations Individuals over 50 Annual faecal occult blood testing OR one colonoscopic examination ( not need to be repeated for 10 years if results are normal)
genetic factors of breast cancer
Genetic factors
Carriers of mutations of several high-penetrance and low frequency genes
BRCA1, BRCA2, PTEN, TP53
High risk breast cancer
Defined as inherited breast cancer syndrome
Cumulative lifetime risk in carriers >50%, but rare in most populations except the AshKenazi Jews
Moderate risk
Group of low penetrance and low frequency DNA repair genes
Similarities and differences in risk profiles between TNBC and ER+ breast cancer
Similar risk factors
BMI
Lack of physical activity
Breast density
risk factors of Breast cancer
Causes and risk factors
Endogenous hormones
Oestradiol concentrations in post-menopausal women; not so distinct in pre-menopausal
Gender
Less than 1% occur in men
Risk factors: conditions involving high oestrogen levels
Gonadal dysfunction
Alcohol abuse
Obesity
Genetics: BRCA2 mutations more common than BRCA1 in male familial breast cancers
Little evidence for geographic and interracial variations
Fibrocystic disease and fibroadenoma
Not pre-neoplastic
Share with breast cancer epithelial proliferation, linked to hormonal alterations
History of breast cancer in a first degree relative
Role of family history related to low penetrance genes associated with hormonal metabolism and regulation, and DNA damage and repair
Nulliparity
TNBC triple negative: Decreased risk
ER+: Increased risk
Number of deaths
TNBC triple negative: Positively associated
ER+: Inversely associated
Age at mernache and menopause
TNBC triple negative: No association
ER+: Modestely association
Tobacco
TNBC triple negative: No association
ER+: Risk factor
Alcohol
TNBC triple negative: Protective
ER+ : Risk factor
Breast cancer prevention
Primary
Control of weight gain especially in post menopausal women
Secondary Mammography Effective in patients >50 years. Not well demonstrated for <50 Breast self examination No proven reduction in mortality
Protective factors of breast cancer
Protective factors
Physical exercise
Esophageal cancer histology
high risk areas
Squamous cell carcinoma (SqCC)
Decreasing incidence
Adenocarcinoma of lower oesophagus
On the rise
Esophageal cancer prevention
Prevention SqCC Avoidance of smoking Reduction in alcohol drinking Improved diet Increased consumption of fresh fruits and vegetables Adenocarcinoma Avoidance of smoking Control of obesity Increased physical activity Treatment of reflux
Adenocarcinoma of esophageal cancer
Adenocarcinoma
Lower third of oesophagus
Increasing incidence among white people and high social classes
Preneoplastic
Barret’s oesophagus-columnar metaplasia of epithelium
Main risk factor: persistent reflux oesophagitis
Overwight
Lack of physical activity
Tobacco smoking
Salty foods
Protective factor: high intake of fruits and vegetables
Esophageal risks and causes
Risk factors and causes 90% SqCC from tobacco smoking and alcohol drinking in HICs Smoking Quitting smoking reduces the risk Smoking black tobacco, high-tar, hand-rolled cigarettes, pipes, chewing tobacco Snuff use Genetic factors Genes responsible for keratosis palmaris and plantaris(tylosis) Mycotoxins and N-nitroso compounds Eating Bracken fern Ionizing radiation Radiotherapy for breast cancer
Other Risk factors and causes of esophageal cancer
Risk factors and causes
Diet rich in foods from animal origin and poor in vitamins and fibre
Low intake of fresh fruits and vegetables
Low intake of fish
High intake of red meat and processed meat
Plummer-Vinson syndrome
Sideropenic dysphagia
Deficit of iron, riboflavin, and other vitamins
Coeliac disease
Nutritional deficiencies
Family history of oesophageal cancer
Normal characteristics of benign
Normal characteristics Amenable to surgery Minor symptoms Fatal Compression Difficult area for surgery Production of hormones
