1ª Aula-Epidemiologia e noções sobre a _natureza do cancro_-2012

7/31/2019 1 Aula-Epidemiologia e noes sobre a _natureza do cancro_-2012

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Epidemiologia e noes principais sobre a Natureza do Cancro

(Epidemiology and major concepts about the Nature of Cancer)

Oncobiologia 2012FML


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Lung; 1608055;

12%

Breast; 1384155;

11%

Colorectum;

1235108; 10%

Stomach; 988602;

8%

Prostate; 899102;

7%Liver; 749744; 6%

Cervix uteri;

530232; 4%

Oesophagus;481645; 4%

Bladder; 382660;

3%

Other; 4403251;

35%

World Incidence New cases - 2008

All cancers excl. non-melanoma skin cancer New cases 12 662 554

SOURCE: GLOBOCAN 2008IARC


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Lung; 1376579;

18%

Stomach; 737419;

10%

Liver; 695726; 9%

Colorectum;

609051; 8%Breast; 458503;

6%Oesophagus;

406533; 5%

Cervix uteri;

275008; 4%

Pancreas; 266669;

4%

Prostate; 258133;

3%

Other; 2481181;

33%

World Mortality - Deaths - 2008

All cancers excl. non-melanoma skin cancer - Deaths 7 564 802



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223,2246,9

264,3 255,8

181,6

106,3117,3 114,7 111,1 106,1

0

50

100

150

200

250

300

PORTUGAL EUROPE EUROPEAN

UNION (EU-27)

MORE

DEVELOPED

REGIONS

WORLD

New cases Age-standardised rate (W)/105 Inhabitants

Deaths Age-standardised rate (W)/105 Inhabitants

2008

New cases Age-standardised rate (W) Deaths Age-standardised rate (W)



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40,6

37,0

41,6 40,8 40,8 40,4

0,0

5,0

10,0

15,0

20,0

25,0

30,0

35,0

40,045,0

Colorectum Breast Prostate Lung Stomach All cancers excl.

non-melanoma

skin cancer

Portugal 2008-2030

Estimated number of new cancers (all ages)

Growing rate (%)

All ages Ages < 65 Ages >= 65



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43284

44422

47185

50031

52981

55783

24302

25061

26830

28579

30616

32693

0 20000 40000 60000 80000

2008

2010

2015

2020

2025

2030

New cases Deaths

Portugal 2008 2030

Estimated number of new cancers

Estimated number of cancer deaths

Year



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Colorectum;6952; 16%

Breast; 5333;

12%

Prostate;5140; 12%

Lung; 3288;

8%

Stomach;

2889; 7%

Other; 19682;

45%

2008

Colorectum;

9333; 17%

Breast; 6312;11%

Prostate; 7145;

13%

Lung; 4374; 8%Stomach; 3809;

7%

Other; 24810;44%

2030

SOURCE: GLOBOCAN 2008 -IARC


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10,4

15,8

14,6

15,2

13,5

13,7

16,4

31,4

50,1

60,0

0 10 20 30 40 50 60

Stomach

Lung

Colorectum

Prostate

Breast

Portugal 2008New cases Age-standardised rate (W)/105 Inhabitants

Deaths Age-standardised rate (W)/105 Inhabitants

Incidence ASR (W) Mortality ASR (W)



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Ten Leading Cancer Types for the Estimated New Cancer Cases and Deaths By Sex,United States, 2011

CA CANCER J CLIN 2011;61:212236


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Ten Leading Cancer Types for the Estimated New Cancer Cases and Deaths By Sex,United States, 2011



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The Demographics and Epidemiology of Cancer

Populations in developed countries are aging rapidly.


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The Demographics and Epidemiology of Cancer

-the number of elderly has increased steadily over the past century

-the age-adjusted death rate of most cancers has been relatively constant

for many decades


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Luis Costa

The best kept secret today, is that cancers,as a group, are among the most curable ofchronic disease.

Vincent T. DeVita


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T.Murray, E. Ward et al., CA Cancer J. Clin. 55:10-30, 2005


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T.Murray, E. Ward et al., CA Cancer J. Clin. 55:10-30, 2005


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16

Burden of breast cancer

More than 1 million new cases diagnosed in 2000 worldwide1,2

Estimated global 5-year prevalence: 3.9 million1

1 in 8 lifetime risk in women3

Leading cause of cancer death in women worldwide2

1. Ferlay et al. GLOBOCAN 2000: Cancer incidence, mortality and prevalence worldwide, version 1.0. Lyon,

IARCPress. 2001. 2. Shibuya et al. BMC Cancer2002; 2:37. 3. Ries et al. SEER Cancer Statistics Review,1975-2001. Available at: http://seer.cancer.gov/csr/1975_2001. 2004.


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BMJ, 2008


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Incidence and Mortality Rates of Female Breast Cancer by Age, United States,1975 to 2008



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Luis Costa

Geographic variation in cancer incidence and death rates

Which of the two alternatives heredity or environment is the

dominant determinant of the country-to-country variabilityof cancer incidence?


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Country-to-country comparisions of cancer incidence


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The great majority of cancers are caused by factors or agentsthat are external to the body, enter into the bodyand corrupt its tissues.



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Proctor, Nat. Rev. Cancer1:82-86; 2001


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Conceptual model for understanding mechanisms of tobacco

carcinogenesis. PKA, protein kinase A.

DeVita, 2008

Tobacco and Lung Cancer


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The Nature of Cancer


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Proofs of tumor monoclonality: all of the cancer cells in a tumor arising in aG6DP heterozygous patient express either one or the other form of this enzyme

Open question?


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Tumors arise from normal tissues

Histopathology: tumors , like normal tissues, are composed of masses of cells

Cancer cells have a quite different and more focused agenda:Making more copies of themselves new colonies

Primary/ metastases

Liver metastasesfrom colon cancer

Brain metastasesfrom breast cancer

Hyperplastic Dysplastic Neoplastic

Metastatic


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Intraductal carcinoma(DCIS)

Invasive carcinoma

Pre-malignant Malignant phenotype


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Histopathology Principles

All tumors should, in principle, be traceable back to the specifictissue or organ site in which they first arose

Tumors are classificable

Carcinomas / sarcomas hematopoietic tumors

Correlate behavior with microscopic features

benign / malignant

What is going to happen with me?


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(> 80% of cancer-related deaths in western world)

Mesoderm origen


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Osteosarcoma Liposarcoma Leiomyosarcoma

Lung metastases(< 2 years)

Local relapse Lung metastases(Long time to relapse)

Chromossomal Translocations in Sarcomas


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Chromossomal Translocations in Sarcomas

V l f C i A l i i h T f


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Value of Cytogenetic Analysis in the Treatment ofDermatofibrosarcoma Protuberans

JCO, April 2008

Translocation t(17;22) was confirmed using caryotype showing asupernumerary ring chromosome (Fig 2, A).

Fluorescent in situ hybridization (FISH) analysis on interphase cell nucleishowing the merged green-red signals corresponding to collagen 1A1promoter (COL1A1)platelet-derived growth factor-B (PDGF) fusion gene(Fig 2, B),

V l f C t ti A l i i th T t t f


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Value of Cytogenetic Analysis in the Treatment ofDermatofibrosarcoma Protuberans

JCO, April 2008

Treatment response to Imatinib


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Small cell

carcinomas

Melanomas

Anaplastic

tumors

Carcinomas:

Adenocarcinoma

Squamous cell

Sarcomas

Neuroectodermal

Malignancies:

Glioblastoma

Retinoblastoma

Hematopoietic

malignancies

Histology

Clinical BehaviourTreatment specificity

Cancer Biology

Molecular MedicineIndividualized Therapy


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Cancer cellResistance toAnti proliferativesignals

Cell Imortalization

Inhibition ofapoptosis

Angiogenesis

Capacity to invadeand metastasize

Growth factors (oncoproteins)Transduction signaling alterations

Cancer: proliferation; dedifferentiation; invasiveness; metastases

What is common in Cancer Nature?


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Os cancros so devidos a

-Factores genticos ?-Factores do ambiente (carcinognios) ?

-Ambos ?


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Cancer is caused by mis-regulation of gene expression


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A limited number of acquired phenotypesin all cancers

Cancers generate their own mitogenic signals,Resist exogenous growth-inhibitory signals,

Evade apoptosis,Proliferate without limits,Acquire vasculatureInvade and metastasize


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Point mutations in the 12th 13th or 61st codon result in activated Ras protein


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Figure 4.10 The Biology of Cancer( Garland Science 2007)

Point mutations in the 12th, 13th, or 61st codon result in activated Ras protein(detected in more than one-fifth of all human cancers)


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The absence of p53-triggered responses to geneticdamage will permit the survival of cells

that are accumulating mutationsat a greater-than-normal rate


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Control of pRB function is perturbed in most if not allhuman cancers

Deregulation of the pRB pathway leads to unconstrainedproliferation


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Cancer cells need to become immortal

in order to form tumors

85 to 90% of human tumors are telomerase-positive

The remaining 10-15% have an alternative lengtheningof telomeres, ALT mechanism to construct and maintain

their telomeres


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How to make a human cancer cell?


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How to make a human cancer cell?

1. Express protein that inactivates pRB and p53

2. Activate telomerase expression

3. Express active ras


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The Biology of CancerFirst Edition

Robert A. Weinberg

Copyright Garland Science 2007


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Figure 5.1 The Biology of Cancer( Garland Science 2007)


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1ª Aula-Epidemiologia e noções sobre a _natureza do cancro_-2012