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EPIDEMIOLOGIA
ANALITICA O
INVESTIGATIVA
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AMBIENTEUOMO
MALATTIA
Diade di Ippocrate
INFETTIVA
AGENTE
EZIOLOGICO
Causa necessariama non sufficiente
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FATTORI DI
RISCHIO
MALATTIE
FR 1 M 1
M 2
M 3
M 4
FR 1
FR 2FR 2
FR 3FR 3
FR 4FR 4
M 1
M 2
M 3
M 4
FATTORI DI
RISCHIO
MALATTIE
INTERAZIONI
Effetti additiviSinergismi
Antagonismi
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FATTORI
PROTETTIVI
MALATTIE
FP 1 M 1
M 2
M 3
M 4
FP 1
FP 2FP 2
FP 3FP 3
FP 4FP 4
M 1
M 2
M 3
M 4
MALATTIEFATTORI
PROTETTIVI
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FATTORI DI RISCHIOCANCEROGENO DI NATURA
BIOLOGICA, MECCANICA,FISICA E CHIMICA
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THE PREVENTION OF INFECTIONASSOCIATED CANCERS
Pathogen Main asociated cancerIARC
Group
Hepatocellular carcinoma
Hepatitis viruses
HBV
HCV
HDV
1
1
3
Hepatocellular carcinoma
None
(S. De Flora and P. Bonanni, Carcinogenesis 32, 787-795,
2011)
Pathogen Main asociated cancerIARC
Group
4.9% of all cancers
85.5% of all HCCs
4.9% of all cancers4.9% of all cancers
85.5% of all HCCs85.5% of all HCCs
Infectious agents cause 17% of all cancers
worldwide, 26% in developing world,
8% in developed world
D.M. Parkin, Int.J.Cancer 15, 3030D.M. Parkin, Int.J.Cancer 15, 3030--44, 200544, 2005
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HBV INFECTION AND PRIMARY
HEPATOCELLULAR CARCINOMA
Insertional mutagenesis, i.e., integration of HBV DNA into thecellular genome, in proximity of genes involved in cellproliferation and/or differentiation
Transcriptional transactivation, i.e., induction of cellularoncogenes (e.g., c-mic, c-fos) by HBV gene products (e.g.,HBxAg)
Deletion or mutation of tumor suppressor genes (e.g.,p53)
Liver cirrhosis, with inflammation, necrosis and regeneration
Enhanced metabolic activation of chemicalhepatocarcinogens (e.g., aflatoxin B1, food pyrolysisproducts)
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Rischio relativo
HBV 7,3
AFB1 3,4
HBV + AFB1 60,0DANNO AL DNAE INIZIAZIONEDEL CANCRO
AUMENTATO METABOLISMODI EPATOCANCEROGENICHIMICI
O O
O
O O
OCH3
CH3
N
N
NH2
AFB1
Trp-P-2
In collaborazione con:1Catt. Gastroenterologia, ISMI, Universit di Genova2Ist. Fisiologia Generale, Universit di Genova3Institute for Cancer Research, Philadelphia, PA, USA4International Agency for Research on Cancer (IARC), Lyon, France5National Cancer Institute (NCI), Bethesda, MD, USA6Environmental Protection Agency (EPA), Research Triangle Park, NC, USA7Integrated Laboratory Systems, Research Triangle Park, NC, USA
Nellepatite B umana (HBV) e animale (WHV)
vi un esaltato metabolismo di epatocancerogeni chimici
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THE PREVENTION OF INFECTIONASSOCIATED CANCERS
Pathogen Main asociated cancer
Hepatitis viruses
HBV
IARCGroup
HCV
HDV
1
1
3
Hepatocellular carcinoma
Hepatocellular carcinoma
None
(S. De Flora and P. Bonanni, Carcinogenesis 32, 787-795,
2011)
Pathogen Main asociated cancerIARCGroup
Papillomaviruses HPV
HPV type 16
HPV types 18, 31, 33, 35,39, 45, 51, 52, 56, 58, 59
HPV type 68
1
1
2A
Cancers at several sites
Cervical cancer
Cervical cancer
HPV types 26, 30, 34, 53,66, 67, 69, 70, 73, 82, 85, 97 2B Cervical cancer
HPV type 5 and 8 2B Skin cancer HPV type 6 and 11 3 None
Other and HPV types 3 None
4.9% of all cancers
85.5% of all HCCs
4.9% of all cancers4.9% of all cancers
85.5% of all HCCs85.5% of all HCCs
5.2% of all cancers
100% of cervix cancers
5.2% of all cancers5.2% of all cancers
100% of cervix cancers100% of cervix cancers
Infectious agents cause 17% of all cancers
worldwide, 26% in developing world,
8% in developed world
D.M. Parkin, Int.J.Cancer 15, 3030D.M. Parkin, Int.J.Cancer 15, 3030--44, 200544, 2005
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Pathogen Main asociated cancer
Hepatitis viruses
HBV
IARCGroup
HCV
HDV
1
1
3
Hepatocellular carcinoma
Hepatocellular carcinoma
None
HPV type 16
HPV types 18, 31, 33, 35,39, 45, 51, 52, 56, 58, 59
HPV type 68
1
1
2A
Cancers at several sites
Cervical cancer
Cervical cancer
HPV types 26, 30, 34, 53,66, 67, 69, 70, 73, 82, 85, 97 2B Cervical cancer
HPV type 5 and 8 2B Skin cancer HPV type 6 and 11 3 None
Pathogen Main asociated cancerIARCGroup
Other and HPV types 3 None
Polyomaviruses
JCV NA CNS tumors and colorectalcancer?
MCV NA Skin cancer (Merkel cell
carcinoma)SV40 NA Malignant mesothelioma ?
Herpesviruses
EBV or HHV4 1 Burkitts lymphoma, sinonasalangiocentric T-cell lymphoma,immunosuppressor-related non-Hodgkins lymphoma, Hodgkinslymphoma, nasopharyngeal
carcinomaKSHV or HHV8 1 Kaposis sarcoma, primary
effusion lymphoma
Retroviruses
HTLV-I
HTLV-II
HIV-I
1
3
1
Adult T-cell leukemia/lymphoma
None
Kaposis sarcoma, non-Hdgkins
lymphoma, Hodgkins lymphoma,cervical cancer, anus cancer,conjunctive cancer
HIV-II 2B Kaposis sarcoma, non-Hodgkinslymphoma
HERV-K NA Human breast cancer
THE PREVENTION OF INFECTIONASSOCIATED CANCERS(S. De Flora and P. Bonanni, Carcinogenesis 32, 787-795,
2011)
Infectious agents cause 17% of all cancers
worldwide, 26% in developing world,
8% in developed world
D.M. Parkin, Int.J.Cancer 15, 3030D.M. Parkin, Int.J.Cancer 15, 3030--44, 200544, 2005
4.9% of all cancers
85.5% of all HCCs
4.9% of all cancers4.9% of all cancers
85.5% of all HCCs85.5% of all HCCs
5.2% of all cancers
100% of cervix cancers
5.2% of all cancers5.2% of all cancers
100% of cervix cancers100% of cervix cancers
Papillomaviruses HPV
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THE PREVENTION OF INFECTIONASSOCIATED CANCERS
Pathogen Main asociated cancer
Hepatitis viruses
HBV
IARCGroup
HCV
HDV
1
1
3
Hepatocellular carcinoma
Hepatocellular carcinoma
None
Papillomaviruses HPV
HPV type 16
HPV types 18, 31, 33, 35,39, 45, 51, 52, 56, 58, 59
HPV type 68
1
1
2A
Cancers at several sites
Cervical cancer
Cervical cancer
HPV types 26, 30, 34, 53,66, 67, 69, 70, 73, 82, 85, 97 2B Cervical cancer
(S. De Flora and P. Bonanni, Carcinogenesis 32, 787-795,
2011)
HPV type 5 and 8 2B Skin cancer HPV type 6 and 11 3 None
Pathogen Main asociated cancerIARCGroup
Other and HPV types 3 None
Polyomaviruses
JCV NA CNS tumors and colorectalcancer?
MCV NA Skin cancer (Merkel cell
carcinoma)SV40 NA Malignant mesothelioma ?
Herpesviruses
EBV or HHV4 1 Burkitts lymphoma, sinonasalangiocentric T-cell lymphoma,immunosuppressor-related non-Hodgkins lymphoma, Hodgkinslymphoma, nasopharyngeal
carcinomaKSHV or HHV8 1 Kaposis sarcoma, primary
effusion lymphoma
Retroviruses
HTLV-I
HTLV-II
HIV-I
1
3
1
Adult T-cell leukemia/lymphoma
None
Kaposis sarcoma, non-Hdgkins
lymphoma, Hodgkins lymphoma,cervical cancer, anus cancer,conjunctive cancer
HIV-II 2B Kaposis sarcoma, non-Hodgkinslymphoma
HERV-K NA Human breast cancer
4.9% of all cancers
85.5% of all HCCs
4.9% of all cancers4.9% of all cancers
85.5% of all HCCs85.5% of all HCCs
5.2% of all cancers
100% of cervix cancers
5.2% of all cancers5.2% of all cancers
100% of cervix cancers100% of cervix cancers
Infectious agents cause 17% of all cancers
worldwide, 26% in developing world,
8% in developed world
D.M. Parkin, Int.J.Cancer 15, 3030D.M. Parkin, Int.J.Cancer 15, 3030--44, 200544, 2005
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THE PREVENTION OF INFECTIONASSOCIATED CANCERS
Pathogen Main asociated cancer
Hepatitis viruses
HBV
IARCGroup
HCV
HDV
1
1
3
Hepatocellular carcinoma
Hepatocellular carcinoma
None
Papillomaviruses HPV
HPV type 16
HPV types 18, 31, 33, 35,39, 45, 51, 52, 56, 58, 59
HPV type 68
1
1
2A
Cancers at several sites
Cervical cancer
Cervical cancer
HPV types 26, 30, 34, 53,66, 67, 69, 70, 73, 82, 85, 97 2B Cervical cancer
(S. De Flora and P. Bonanni, Carcinogenesis 32, 787-795,
2011)
HPV type 5 and 8 2B Skin cancer HPV type 6 and 11 3 None
Pathogen Main asociated cancerIARCGroup
Other and HPV types 3 None
Polyomaviruses
JCV NA CNS tumors and colorectalcancer?
MCV NA Skin cancer (Merkel cell
carcinoma)SV40 NA Malignant mesothelioma ?
Herpesviruses
EBV or HHV4 1 Burkitts lymphoma, sinonasalangiocentric T-cell lymphoma,immunosuppressor-related non-Hodgkins lymphoma, Hodgkinslymphoma, nasopharyngeal
carcinomaKSHV or HHV8 1 Kaposis sarcoma, primary
effusion lymphoma
Retroviruses
HTLV-I
HTLV-II
HIV-I
1
3
1
Adult T-cell leukemia/lymphoma
None
Kaposis sarcoma, non-Hdgkins
lymphoma, Hodgkins lymphoma,cervical cancer, anus cancer,conjunctive cancer
Helicobacter pylori 1 Gastric cancer, MALT
HIV-II 2B Kaposis sarcoma, non-Hodgkinslymphoma
HERV-K NA Human breast cancer
4.9% of all cancers
85.5% of all HCCs
4.9% of all cancers4.9% of all cancers
85.5% of all HCCs85.5% of all HCCs
5.2% of all cancers
100% of cervix cancers
5.2% of all cancers5.2% of all cancers
100% of cervix cancers100% of cervix cancers 5.5% of all cancers
63.4% of stomach cancers
5.5%5.5% ofof allall cancerscancers
63.4%63.4% ofof stomachstomach cancerscancers
Infectious agents cause 17% of all cancers
worldwide, 26% in developing world,
8% in developed world
D.M. Parkin, Int.J.Cancer 15, 3030D.M. Parkin, Int.J.Cancer 15, 3030--44, 200544, 2005
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Helicobacter pylori
Gastric mucosa(119 subjects)
Antibiotic resistance assay
rRNA
genotypes
vacA
GSTM1
OGG1
genotypes
DNAextraction
Gender - AgeStage of gastritisGastric dysplasia
Enteroid metaplasia
8-oxo-dG
cagA
Culture
PCR
It is an extremelyvaluable studywhich could affect,
positively, millionsof human beings
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Pathogen Main asociated cancer
Hepatitis viruses
HBV
IARCGroup
HCV
HDV
1
1
3
Hepatocellular carcinoma
Hepatocellular carcinoma
None
HPV type 16
HPV types 18, 31, 33, 35,39, 45, 51, 52, 56, 58, 59
HPV type 68
1
1
2A
Cancers at several sites
Cervical cancer
Cervical cancer
HPV types 26, 30, 34, 53,66, 67, 69, 70, 73, 82, 85, 97 2B Cervical cancer
HPV type 5 and 8 2B Skin cancer HPV type 6 and 11 3 None
Pathogen Main asociated cancerIARCGroup
Other and HPV types 3 None
Polyomaviruses
JCV NA CNS tumors and colorectalcancer?
MCV NA Skin cancer (Merkel cell
carcinoma)SV40 NA Malignant mesothelioma ?
Herpesviruses
EBV or HHV4 1 Burkitts lymphoma, sinonasalangiocentric T-cell lymphoma,immunosuppressor-related non-Hodgkins lymphoma, Hodgkinslymphoma, nasopharyngeal
carcinomaKSHV or HHV8 1 Kaposis sarcoma, primary
effusion lymphoma
Retroviruses
HTLV-I
HTLV-II
HIV-I
1
3
1
Adult T-cell leukemia/lymphoma
None
Kaposis sarcoma, non-Hdgkins
lymphoma, Hodgkins lymphoma,cervical cancer, anus cancer,conjunctive cancer
Helicobacter pylori 1 Gastric cancer, MALT
HIV-II 2B Kaposis sarcoma, non-Hodgkinslymphoma
HERV-K NA Human breast cancer
Schistosomes
S. haematubium 1 Urinary bladder cancer
S. japonicum 2B Colorectal and liver cancers
S. mansoni 3 None
Liver flukes
Opistorchis viverrini 1 Cholangiocarcinoma
Opistorchis felineus 3 NoneChlonorchis sinensis 1 Cholangiocarcinoma
THE PREVENTION OF INFECTIONASSOCIATED CANCERS(S. De Flora and P. Bonanni, Carcinogenesis 32, 787-795,
2011)
Infectious agents cause 17% of all cancers
worldwide, 26% in developing world,
8% in developed world
D.M. Parkin, Int.J.Cancer 15, 3030D.M. Parkin, Int.J.Cancer 15, 3030--44, 200544, 2005
4.9% of all cancers
85.5% of all HCCs
4.9% of all cancers4.9% of all cancers
85.5% of all HCCs85.5% of all HCCs
5.2% of all cancers
100% of cervix cancers
5.2% of all cancers5.2% of all cancers
100% of cervix cancers100% of cervix cancers 5.5% of all cancers
63.4% of stomach cancers
5.5%5.5% ofof allall cancerscancers
63.4%63.4% ofof stomachstomach cancerscancers
Papillomaviruses HPV
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PREVENZIONE DEI TUMORIASSOCIATI CON INFEZIONI O
INFESTAZIONI CRONICHE
Eradicazione di infezioni (es. H. pylori, HART) oinfestazioni
Vaccini contro virus (es. HBV, HPV, FLV, ecc.)
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S. De Flora et al, Cancer Res. 47, 40528, 1987; Carcinogenesis 10, 10991106, 1989
A.Izzotti et al, Chem.-Biol. Int. 97, 273285, 1995
AFB1
Trp-P-2
HBV
Prevention of
HBV infection
Prevention of
HBV infection
A. Camoirano et al, Cancer Epid. Biol. Biom. 10, 775783, 2001
ChemopreventionChemoprevention
DrugsDrugsDietDiet
Avoidanceof exposure
Avoidanceof exposure
RegulationsRegulations
Healtheducation
Healtheducation
PRIMARY PREVENTIONOF HEPATOCELLULAR
CARCINOMA
PRIMARY PREVENTIONOF HEPATOCELLULAR
CARCINOMA
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AMBIENTE E TUMORI
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AMBIENTEAMBIENTE
"insieme degli elementi che, nella complessit delle loro relazionicostituiscono le condizioni di vita dell'uomo" (EU, 1973)
Luomo, come tutti gli esseri viventi, interagiscecontinuamente con lambiente che pu divenire causa di
effetti negativi sul suo stato di salute.Lequilibrio del rapporto uomo-ambiente
(come risultato dinamico!) stato fortemente influenzatodai progressi socio-economici e
tecnico-scientifici avvenuti nellutlimo secolo.
Sostenibilit ambientale
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AMBIENTE E TUMORI
distribuzione geografica(a)
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STOMACO
POLMONE
MAMMELLA
COLON - RETTO
CERVICE UTERINA
BOCCA - FARINGE
ESOFAGO
FEGATO
LINFOMI
PROSTATA
VESCICA
LEUCEMIE
CORPO UTERO
OVAIO
PANCREAS
LARINGE 67,152,9
90 47,4
70,4 67,2
103,5 45,3
82,7 105,5
148,2 71,2
177,2 58,6
116,1 121,8
59,6 191,6
56,8 253,6
106,2 272,3
96,1 369,5
389,2 182,9
347,9 224,2
454,6 205,9
333 336,4
500 400 300 200 100 0 500400300200100
PAESI SVILUPPATI PAESI IN VIA DI SVILUPPO
NUMERO DI CASI (X 1000)
NUMERO DEI CASI DI CANCRO RELATIVI A 16 SITI ANATOMICI
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CANCRO DELPOLMONE
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CANCRO DELLOSTOMACO
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CANCRO DELLAMAMMELLA
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AMBIENTE E TUMORI
distribuzione geografica(a)
gruppi di popolazione(b)
popolazioni migranti(c)
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TUMORI IN DIVERSE GENERAZIONI DI EMIGRATI
GIAPPONESI CONFRONTATI CON LA POPOLAZIONESTATUNITENSE
Giappone Bianchi U.S.1a 2a 3a
Stomaco + + + + + + + + + + +
Colon e retto + + + + + + + + + + + + + + + +
Mammella + + + + + + + + + + + + +
Prostata + + + + + + + + + + +
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0 - 5 6 - 16 17 +
Anni di residenza
1,6
1,4
1,2
1,0
0,8
0,6
0,4
0,2
0
Mortalit(d
atistandardizzati)
MORTALITA PER CANCRO DELLA MAMMELLA IN DONNE ITALIANEMIGRANTI IN AUSTRALIA (19621971)
donne australiane
MORTALITA PER CANCRO DELLA MAMMELLA IN DONNE ITALIANEMIGRANTI IN AUSTRALIA (19621971)
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AMBIENTE E TUMORI
distribuzione geografica(a)
gruppi di popolazione(b)
popolazioni migranti(c)
variazioni nel tempo(d)
rimozione fattori di rischio(e)
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INCREASING CONSUMPTION OF CIGARETTES IS FOLLOWED BYA STEEP RISE IN DEATHS FROM LUNG CANCER
Lung cancer deaths in England and Wales show a close correlation with thenumber of cigarettes smoked in earlier years. Source: J. Cairns.
MenWomen
Smoking Lung cancer
Smoking
Lung cancer
5000
4000
3000
2000
1000
0
200
150
100
50
0Ann
ualpercapitac
onsumptionofcigarettes
Annua
llungcancerde
athsper100,00
0population
1900 1920 1940 1960 1980
MORTALITA PER TUMORI POLMONARI
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Maschi
MORTALITA PER TUMORI POLMONARI
(DATI STANDARDIZZATI PER 100.000)
90
80
70
60
50
40
30
20
10
0
1965-69 70-74 75-79 80-84 85-89 92
UK
USA
UNGHERIA
ITALIA
GIAPPONE
Femmine
30
20
10
0
1965-69 70-74 75-79 80-84 85-89 92
USA
UK
UNGHERIAGIAPPONE
ITALIA
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INTERAZIONIGENE-AMBIENTE