epidemiology in cancer

8/11/2019 Epidemiology in Cancer

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Epidemiology in Cancer


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Picture of Cells Nucleus


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Make a metaphase

or interphase

spread

Identify and line up

each chromosome

pairs side by side

Look for structure

abnormalities

Picture of Chromosomes


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Chromosomes comes in Pair one

from dad and one from mom


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opr05TIB.swf
http://localhost/var/www/apps/conversion/tmp/scratch_8/opr05TIB.swfhttp://localhost/var/www/apps/conversion/tmp/scratch_8/opr05TIB.swf


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Knudsen Two Hits Hypothesis


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Oncogenesis

Statistic based predictionRetinoblastoma is genotypically recessive,only manifest when both Rb gene copies aremutated ie genotype is rb/rb, carrier (i.g.RB/rb) are normal

Descendents from a carrier and a normal

parent theoritically should be 0% forRetinoblastoma

Observation

50% of the children develop

Retinoblastoma

Two Steps (Hits) Oncogenesis

Introduction


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OncogenesisTwo Steps (Hits) Oncogenesis

Introduction

Genotype Clinical

Children

Tumor

Germline

Somatic

0%RB?

50%RB!

2 Hits : Germline inactivating mutation in previous

generation + somatic inactivating mutation in tumor

RB/rb

RB/rb

RB/RB

RB/RB

rb/rb


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Is all cancer one genic?

Nope


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Multistep oncogenesis Pathway


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Animation of Oncogenesis

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kanker\breastcancer.swf
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Rate of genomic Mutations is low

So how is it possible to get cancer if


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So how is it possible to get cancer if

there are too many pathways need to

be disrupted to generate one The persons genome need to be in a state

that is unstable. Easily mutating by

itself!!

= Genomic Instability

Or being mutated continuously from

outside = radiation exposure. Chernobylfor example


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Pathways to malignancy

Genomic Instability Pathway

Barriers are the

two hits

TSG Recql4,

BLM, WRN

OG : any genes

that promote

genomic

instability


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Epid Early detection: So who are

the predisposed group?

People with familial cancer history

Same type of cancer Breast cancer for BRAC1/2

Retinoblastoma MSI and APC for colonic Cancer

Different type of cancer P53

Req1lc Bloom Syndrome

Werner Syndrome


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What to do in the presence ofpredisposing factors?

Regular screening for progression genetic

abnormalities by cytogenetics.

Molecular genetics work up for critical genes in the

absence of cytogenetic evidence

- Southern Blot

- SSCP

Epigenetics work up in the absence of cytogenetic and

genetics evidence.

Regular Radiologic or bone scan work up


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Epidemiology in action