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Pre-Cancerous Pre-Cancerous Lesions: Red Flags Lesions: Red Flags for future Cancers for future Cancers
Gerardo H. Cornelio.MD, FPCP, Gerardo H. Cornelio.MD, FPCP, FPSMO, FPSOFPSMO, FPSO
Magnitude of Cancer Magnitude of Cancer ProblemProblem
in the Philippinesin the PhilippinesINCIDENCEINCIDENCE 3rd in incidence after communicable & 3rd in incidence after communicable &
cardiovascular diseasescardiovascular diseases 1 out of 1,000 Filipinos has cancer1 out of 1,000 Filipinos has cancer 114:103 Females to Males, Filipino114:103 Females to Males, Filipino Incidence rates increase w/ Age:Incidence rates increase w/ Age:
0-14 yr.: 3.6% of cancers0-14 yr.: 3.6% of cancers >35 yr.: 91% of cancers>35 yr.: 91% of cancers >=50 yr.: 76% of cancers>=50 yr.: 76% of cancers
THE TEN LEADING CANCER THE TEN LEADING CANCER SITES IN THE PHILIPPINESSITES IN THE PHILIPPINES
0.00%
2.00%
4.00%
6.00%
8.00%
10.00%
12.00%
14.00%
16.00% LungBreastLiverCervix LeukemiasColonThyroidStomachNasopharynxLymphomas
Philippine Cancer Facts and Estimates, 1998
ESTIMATED LEADING ESTIMATED LEADING CAUSES OF CANCER CAUSES OF CANCER
DEATHSDEATHS
01,0002,0003,0004,0005,0006,0007,0008,0009,000
10,000
# OF CASES
CANCER SITES
LUNG
LIVER
BREAST
CERVIX
COLON
STOMACH
PANCREAS
PROSTATE
RECTUM
Philippine Cancer Facts and Estimates, 1998
TEN LEADING CANCER SITES TEN LEADING CANCER SITES IN MALES IN MALES
LUNG(1)
LIVER(2)
ORAL(10)
RECTUM(9)
LYMPHOMA (8)
NASOPAHRYNX(7)
STOMACH(6)
COLON(5)
LEUKEMIA(4)
PROSTATE (3)
Philippine Cancer Facts and Estimates, 1998
TEN LEADING CANCER SITES TEN LEADING CANCER SITES IN WOMEN IN WOMEN
BREAST(1)
UTERUS(10)STOMACH(9)
LIVER(8)
COLON(7) LEUKEMIAS(6)
OVARY(5)
THYROID(4)
LUNG(3)
CERVIX(2)
Philippine Cancer Facts and Estimates, 1998
What are the Top TenWhat are the Top Ten Cancers in the Philippines? Cancers in the Philippines?Male Female Child
Lung Breast Leukemia (ALL)
Liver Cervix Lymphoma (NHL)
Stomach Lung Brain/ Spinal (Medullablastoma;Astrocytoma)
Colon Ovary Retinoblastoma
Rectum Stomach Bone (Osteosarcoma)
NasopharynxLeukemiaOral cavityPancreas
NHL
LiverThyroid
Oral cavityColon
Rectum
STS (Rhabdo-myosarcoma)Kidney (Wilm’s)Gonadal GCTEpithelioma
CANCERCANCER
MANAGEMENT
Environment
Genetics
Clinical Manifestations
Metastasis
Anaplasia
Proliferation
DIAGNOSISBiopsy
StagingPreventive
Curative
Supportive
THE NINE WARNING THE NINE WARNING SIGNSSIGNS
C
A
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U
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•Change in bowel or bladder habits.
•A sore that does not heal.
•Unusual bleeding or discharge.
•Thickening of a lump in breast or elsewhere.
•Indigestion or difficulty in swallowing.
•Obvious change in a wart or mole.
•Nagging cough or hoarseness.
•Unexplained anemia.
•Sudden, unexplained weight loss.
CANCER CELLS AND CANCER CELLS AND NORMAL CELLSNORMAL CELLS
CANCER CELLS AND CANCER CELLS AND NORMAL CELLSNORMAL CELLS
CANCER CELLSCANCER CELLS NORMAL CELLSNORMAL CELLS
Loss of contact inhibitionLoss of contact inhibition
Increase in growth factor secretionIncrease in growth factor secretion
Increase in oncogene expressionIncrease in oncogene expression
Loss of tumor suppressor genesLoss of tumor suppressor genes
Oncogene expression is rareOncogene expression is rare
Intermittent or co-ordinatedIntermittent or co-ordinatedgrowth factor secretiongrowth factor secretion
Presence of tumor suppressorPresence of tumor suppressorgenesgenes
NormalNormalcellcell
FewFewmitosesmitoses
FrequentFrequentmitosesmitoses
NucleusNucleus
Blood vesselBlood vessel
AbnormalAbnormalheterogeneous cellsheterogeneous cells
Cancer GenesCancer Genes
Proto-oncogenesProto-oncogenes – normally promote – normally promote normal cell growth; mutations normal cell growth; mutations convert them to oncogenes.convert them to oncogenes.
Tumor suppressor genesTumor suppressor genes – normally – normally restrain cell growth; loss of function restrain cell growth; loss of function results in unregulated growth.results in unregulated growth.
DNA repair genesDNA repair genes – when faulty, – when faulty, result in an accumulated rate of result in an accumulated rate of mutations.mutations.
ONCOGENESONCOGENESONCOGENE FUNCTION ASSOCIATED HUMAN CANCER
SIS Platelet-derived growth factorERB1 Epidermal growth factorFMS CSF-1 receptorKIT Stem cell growth factor receptorMET Hepatic growth factor receptor Papillary renal cancerHER2/ NEU/ ERBB2 Heregulin receptor Cancer of breast, ovary, bladder; glioblastomaRET Neurotrophic growth receptor Medullary thyroid cancerTRKA Nerve growth factor receptorERBA Thyroid hormone receptor (nuclear)RAS (H,K,N) GTPase Cancer of lung, pancreas, bladder, colon, rectumBCR-ABL Cytoplasmic tyrosine kinase Chronic myelogenous leukemiaRAF Cytoplasmic tyrosine kinaseSRC Cytoplasmic tyrosine kinase
FOS Transcription factorJUN Transcription factorMYC (c,L,N) Transcription factor Burkitt’s lymphoma, neuroblastoma, lung
cancerBCL6 Transcription factor Large cell lymphomaBCL2 Anti-apoptosis Prostate cancer, lymphoma
CARCINOGENSCARCINOGENS Occupation related causesOccupation related causes Lifestyle related causesLifestyle related causes
TobaccoTobacco DietDiet Sexual practicesSexual practices
Multifactorial causesMultifactorial causes Viral carcinogensViral carcinogens Chemical carcinogensChemical carcinogens Ionizing radiationIonizing radiation
Occupational Risk Occupational Risk FactorsFactors
EtiologyEtiologyArsenicArsenic
AsbestosAsbestos
BenzeneBenzene
BenzedineBenzedine
Chromium cpdsChromium cpds
Radiation (mining)Radiation (mining)
Mustard gasMustard gas
Polycyclic hydrocarbonsPolycyclic hydrocarbons
Vinyl ChlorideVinyl Chloride
Site of MalignancySite of MalignancyLung, skin, liverLung, skin, liver
Mesothelium, lungMesothelium, lung
LeukemiaLeukemia
BladderBladder
LungLung
Numerous locationsNumerous locations
LungLung
Lung, skinLung, skin
Angiosarcoma of liverAngiosarcoma of liver
Lifestyle Risk FactorsLifestyle Risk Factors
Tobacco-related:Tobacco-related: Lung cancerLung cancer Pancreatic cancerPancreatic cancer Bladder cancerBladder cancer Renal cancerRenal cancer Cervical cancerCervical cancer
Diet-Related Risk Diet-Related Risk FactorsFactors
NitratesNitrates
SaltSalt
Low vitamins A, C, ELow vitamins A, C, E
Low consumption of Low consumption of yellow-green yellow-green vegetablesvegetables
Gastric CancerGastric Cancer
Esophageal Esophageal CancerCancer
Diet-Related Risk Diet-Related Risk FactorsFactors
High fatHigh fat
Low fiberLow fiber
Low calciumLow calcium
High boiled or High boiled or fried foodsfried foods
Colon CancerColon Cancer
Pancreatic CancerPancreatic Cancer
Prostate CancerProstate Cancer
Breast CancerBreast Cancer
Uterine CancerUterine Cancer
MycotoxinsMycotoxins Liver CancerLiver Cancer
Sexual Practices Risk Sexual Practices Risk FactorsFactors
Cervical CancerCervical Cancer
Sexual promiscuitySexual promiscuity
Multiple partnersMultiple partners
Unsafe SexUnsafe Sex
Human Human PapillomavirusPapillomavirus
Multifactorial FactorsMultifactorial Factors
Tobacco + AlcoholTobacco + AlcoholOral Cavity CancerOral Cavity Cancer
Esophageal CancerEsophageal Cancer
Tobacco + AsbestosTobacco + Asbestos
Tobacco + miningTobacco + mining
Tobacco + uranium Tobacco + uranium + radium+ radium
Respiratory Respiratory Tract CancerTract Cancer
Lung CancerLung Cancer
Chemical Chemical CarcinogenesisCarcinogenesis
Chemical Chemical CarcinogenCarcinogen
Promoter(s)Promoter(s)
Initiator(s)Initiator(s)(electrophilic, mutagenic)(electrophilic, mutagenic)
Normal CellsNormal Cells
Inactive MetabolitesInactive Metabolites
Initiated CellsInitiated Cells
Tumor CellsTumor Cells
ClonesClones
Gross TumorsGross Tumors
Radiation CarcinogenesisRadiation Carcinogenesis
Radiation-induced mutation in the Radiation-induced mutation in the host cellhost cell
Transmits irreversible changes in Transmits irreversible changes in gene expression to cell progenygene expression to cell progeny
Sources of Potentially Sources of Potentially Carcinogenic RadiationCarcinogenic Radiation
SunlightSunlight Artificial sources of UV lightArtificial sources of UV light X-raysX-rays Radio-chemicalsRadio-chemicals Nuclear fissionNuclear fission
Viral CarcinogenesisViral Carcinogenesis Viral carcinogens are classified Viral carcinogens are classified
into RNA and DNA viruses.into RNA and DNA viruses.
Most RNA oncogenic viruses Most RNA oncogenic viruses belong to the family of belong to the family of retroviruses that contain retroviruses that contain reverse reverse transcriptasetranscriptase mediates mediates transfer of viral RNA into virus transfer of viral RNA into virus specific DNA. specific DNA.
Sequence of Disease Sequence of Disease ProgressionProgression
Leukoplakia / ErythroplakiaLeukoplakia / Erythroplakia
DysplasiaDysplasia
Carcinoma in situCarcinoma in situ
Invasive CarcinomaInvasive Carcinoma
Regional / Distant MetastasisRegional / Distant Metastasis
Lung Cancer ProfileLung Cancer ProfileSmoke: 25 or moreSmoke: 25 or more
15 – 2415 – 24
14 or lower14 or lower
+ 50+ 50
+ 25+ 25
+ 10+ 10
1 or more cigars the past year1 or more cigars the past year + 5+ 5
3 or more vegetables a day3 or more vegetables a day - 5- 5
Parent, brother or sister w lung cancerParent, brother or sister w lung cancer + 10+ 10
Lived with a smokerLived with a smoker + 5+ 5
Live near a large city for 10 yearsLive near a large city for 10 years + 5+ 5
Asbestos worker without protection 5-20 yrs/ >20Asbestos worker without protection 5-20 yrs/ >20 +25 /50+25 /50
Radon, Cadmium, aluminum, silica, sulfur 5-20 />20Radon, Cadmium, aluminum, silica, sulfur 5-20 />20 +10 / 25+10 / 25
Eats 3 or more servings of fruits per dayEats 3 or more servings of fruits per day - 5- 5
Risk ChartRisk ChartScoreScore Your risk is:Your risk is:
Less than 0Less than 0 Very much below averageVery much below average
0 - 60 - 6 Much below averageMuch below average
7 - 107 - 10 Below averageBelow average
11 - 1211 - 12 AverageAverage
13 - 2113 - 21 Above averageAbove average
22 - 5322 - 53 Much above averageMuch above average
54 or higher54 or higher Very much above averageVery much above average
Lung CancerLung Cancer
Bronchial intraepithelial lesionsBronchial intraepithelial lesions
Squamous metaplasia or dysplasia in Squamous metaplasia or dysplasia in former smokersformer smokers
Loss of retinoic acid receptor-B Loss of retinoic acid receptor-B expressionexpression
BREAST CANCERBREAST CANCERSigns and symptoms at Signs and symptoms at
presentationpresentation Mass or painMass or pain
in the axillain the axilla
Palpable massPalpable mass ThickeningThickening PainPain
Nipple dischargeNipple discharge Nipple retractionNipple retraction
Edema or erythemaEdema or erythema
of the skinof the skin
Non Invasive Breast Non Invasive Breast CancerCancer
Lobular Carcinoma in situ (LCIS)Lobular Carcinoma in situ (LCIS) PremalignantPremalignant 20% develop IBC over 15 years20% develop IBC over 15 years 30% bilateral30% bilateral Annual mammography / Tamoxifen risk Annual mammography / Tamoxifen risk
reduction (56%) – NSABP P1reduction (56%) – NSABP P1 Ductal Carcinoma in situ (DCIS)Ductal Carcinoma in situ (DCIS)
MalignantMalignant Recurs in 35% in 10-15 yrs if biopsy aloneRecurs in 35% in 10-15 yrs if biopsy alone >25% develop IBC>25% develop IBC
BREAST CANCERBREAST CANCERSigns and symptoms at Signs and symptoms at
presentationpresentation Mass or painMass or pain
in the axillain the axilla
Palpable massPalpable mass ThickeningThickening PainPain
Nipple dischargeNipple discharge Nipple retractionNipple retraction
Edema or erythemaEdema or erythema
of the skinof the skin
BREAST CANCERBREAST CANCERSigns and symptoms at Signs and symptoms at
presentationpresentation Mass or painMass or pain
in the axillain the axilla
Palpable massPalpable mass ThickeningThickening PainPain
Nipple dischargeNipple discharge Nipple retractionNipple retraction
Edema or erythemaEdema or erythema
of the skinof the skin
Colorectal CancerColorectal Cancer
PhilippinesPhilippines 33rdrd leading cancer site leading cancer site
33rdrd in males in males 44thth in females in females
4rth leading cause of death4rth leading cause of death
COLON CANCERCOLON CANCERFlexible sigmoidoscopyFlexible sigmoidoscopy
Dr Larpent, Clermont-Ferrand; CNRI.
All rights reserved.
Precancerous LesionsPrecancerous Lesions
G-E JunctionG-E Junction KidneyKidney
GERD / Acid refluxGERD / Acid reflux Intratubular Intratubular epithelial epithelial dysplasiadysplasia
H. Pylori infection H. Pylori infection
Genital WartsGenital Warts
Human Papilloma VirusHuman Papilloma Virus Main risk factor for cervical cancerMain risk factor for cervical cancer
Treatment:Treatment: VaccineVaccine Early detectionEarly detection
SkinSkin
Actinic keratosisActinic keratosis Atypical or dysplastic neviAtypical or dysplastic nevi Premalignant LentigoPremalignant Lentigo
Causes:Causes: UV radiationUV radiation GeneticsGenetics Exposure to carcinogens like Arsenic, Tar, Exposure to carcinogens like Arsenic, Tar,
X-rayX-ray