???????? Epidemiology of Cancer

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???????? Epidemiology of Cancer
?????????????? Department of epidemiology
,Harbin Medical University
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? ? (Status)

• ????(Cancer)??????????????,?100????????????
  ??,??????????????????????,????????????????????????
  2015?,??????????900?,?????1500?,????????????????

In 201515x106 people suffer from cancer 2/3
in developing country Motility will reach to
9x106
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?? (Introduction) ???????????? (Study method of
epidemiology) ?????????? (Prevelence states)
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• ????????????
• (Cancer prevelence of China)
• ?????????
• (Risk factors of cancer)
• ???????
• (Prevention of cancer)

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??
(Concept)

• ????????????????????????????,????,???????????
  ?????????

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Definition

• (1) Cancer epidemiology is the study of
• the pattern of cancer in populations.
• (2) Its essential aim is to identify causes of
  cancer, including preventable (avoidable) causes
  and inherited tumor susceptibility.

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• (3) It is also play an critical role in many
• other areas of cancer research including
• evaluation of screening effects, cancer
• prevention and control
• (4) Current studies directions includes
• molecular and genetic epidemiology of
• cancer.

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??? ? ?(Introduction)

• ? ?????
• ?????????????????????????????????

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1.??????????(Pathological Features )

• 1)??(cell) ?????????????????????(differentiatio
  n)?????,????????????????,?????

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Molecular pathologic Technology and immune
chemistry methods

• ??????????????DNA?????????????????????????
  ????
• ????????????????????????????????????,??????
  ????,??????????????????p53????????????????????

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DNA Technique

• DNA??????????????????????,???????????????????
  ???????????

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• 2)????(Biomarker)???????????????????,???????
  ???????????????????????

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• 3)??????????(classification)
• ??????????????????(T),?????(N)????????????(
  M)3?????????????,??pTNM???
• ??T????????????,N???????????,M??????????

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• ???????(classification)????????????,????????
  ???????????????????????????????,????????????
• ???????????3????,????????,???????,??????????
  ?????,???????????3??????????????

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2.????????????(Biological characteristics)

• ????(gene expression)?????(Cell cycle
  )?????????????,?????????????????????????????????

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???????? (Biological characteristics)

• ???? ?? ?? ???? ??
• ???? ? ??
• ??? ? ?? - -
• ?????????(Immortality ),???(Invasiveness),???(Spre
  ading )

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???????(Origin of tumor)

• ?????(Monoclonal theory)
• ????????????????????????????????????????????
  (stem-cell)????????????,??????? ??
  ??????????(BAC),???,???,?????????????k-ras????????
  

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?????(Polyclonal theory)

• ??????????????????
• ???????????(Genetic analysis )
• ?????????????,?APC???Mshz
• ??????????

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???????????
(Origin of Single center or Multi center)

• ?????(???)
• ???????????????????????,???????????????
• ?????(???)
• ?????????????????,?????,???,?????????????????
• ???????????????

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??? (Oncogene)

• ??????????,??????????.
• ????????????,????????,?????????,??,????,??????????
  ??
• ??????????????????,?????????DNA????????????????

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?????(Discovery of oncogene)

• 1911? Rous???????(RSV)???????????,?????????
• 1976??RVS??????src??????????,????V-onc?
• 1982??????????????????ras??????? C-onc?

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?????(c-onc)

• 1976?,Bishop?Rous?????????src,????????????????????
  ??????????????????????,?????????????
• ?????????????

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??????? (Mechanisms )

• ???
• ????ras ??189??????????????????????????,?ras
  gene ???,ras ??????????,?????
• ras proto-oncogene
• 1 12 61 189
• gly gln
• ?
• arg ( G ?C), k-ras oncogene

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??????(Types of Oncogene)

• abl
• bcl
• erb
• fos
• myc
• ras
• sis
• src
• ?100???

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???????
(Sites of oncogene)

• Gene c-onc protein v-onc protein
• src ? ?
• ras ? ?
• myc ? ?
• fps ? ???
• abl ? ?

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??????????(Mechanism of Oncogene)

• ?????
• ras??12??????,G-T
• arg-val, ras???GTP??,
• ?????????
• ras ????????,????????
• ras?CCGG???????,?????????

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ras ?????
(Family members of ras)

• ??????,??????????,?ras????????
• H-ras 11p15.5 ?? ??? ???
• N-ras 1p13.2 ??? ??
• K-ras 12p12.1 ??? ??? ??

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????(Cancer-inducing virus)

• ? ? ???? ???
• ????? ????DNA T????
• ??? ????DNA E1A,E1B
• ???? ????DNA EB??
• ????? ??RNA ras,src?

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??????(tumor suppressor gene)

• ??????????????,??????????,??????????????????????
  ,???????????,???????????????
• 1968?Harris??
• ???? X ????
• ???????
• ?? ??? (???????)

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???????????(First discovered Tumor Suppressor
Gene)

• ???????
• ??Rb?????????,??????,???????????????????????
  ?Rb?????????Rb???????????????,??Rb????????
• del(13) (q14)

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??????????????(Study methods of Cancer
Epidemiology)

• ??????????,??????,????????????????????,?????
  ???????????????????????????,??????????????????????
  ???,?????????,?????????????????,??????????????????
  ????????

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???????????????

• ??????????????????????????????
• ?????????????????????????????????
• ??????????????????????????????,???????????????????
  ??????

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• ?????????????????????
• ??????????????????????,???????

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???????? (Descriptive epidemiologic study)

To describe the difference in occurrence
of a particular cancer between different groups
(age, gender, race, country, a period of time
for time trend) and to generate the hypothesis
for increased/decreased for the specific tumor
type.
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• ???????????(health information system,HIS)
  ????????????????????????????????????,?????????????
  ?HIS????????????????????????????????????????????
  ????????,?????????

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                                                                                                        2004?8?9?856 --
                                                                                                                                                                                                                                                                                                                                                                                                                    
2004/07/15?????????????????????????? ???????????????????????????,??????????????????????????????,?????????????????????(??????),??2004?6?10????????????????????????????????????,????????????????????????????????????????????????????????????????????,?????????????,?????????????????(??????)????????,????????????????????????????? ?????????????????????????,????????????,??????2004??????
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• ????????????????,???????????????????????????
  ?,???????????????????????????????,????????????????
  ?????????????

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• ??????????????????????????????????,?????????
  ???,??????????????,?????????????

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???????? (Analytic epidemiological study)

• ?????????????????????????????????????????
• ??????????????????????????????????????????????

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• ?????????????????????????????????????????NCI?????
  ?1998???,1999????????????,??1997?????????????????
  ???????2000??????????????????????????????????????
  ?,???????????????????????????????????

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????????
(Experimental epidemiological study)

• ???????????????,?????????????????????????????

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• ??????????????????????,???????????????NCI??
  ???????????????????,??????????????????????????????
  ??????32902?,???????????????????????????????????1
  998???,????2213?,??????????????,??????????????????
  ???????????????????????????,?????????????????,????
  ???????????

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?????????????
(Biomarker and tumor epidemiological study)

• ????????????????????????????,???????????????
  ????????????????

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??????
(Types of Biomarker)

• ????(In doses )
• ????????(Biological effective dose)
• ??????????(Pre-clinical biological effects )
• ??????(Susceptibility marker )
• ????????????????

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Molecular Epidemiology
Breaking Open the Black Box
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Molecular Epidemiology
Exposure
Disease
Biological Effective Dose (Adducts)
Preclinical Biologic Effect (SCE oncogene TSG
inactivation)
Internal Dose (Agent Metabolite)
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• ??? ?????????
• (?????????)

Epidemiological Characteristics of Malignancy
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Measures of Cancer Frequency Incidence

• number of new cases occurring
• can be expressed as an absolute number of cases
  per year or as a rate per 100,000 persons per
  year.
• incidence rate provides approximation to average
  risk of developing a cancer and is necessary to
  compare risk of disease between populations
• reduction in incidence is the appropriate
  statistics to use when considering impact of
  primary prevention strategies

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Measures of Cancer Frequency Mortality

• number of deaths occurring
• mortality rate is the number of deaths per
  100,000 persons per year
• mortality rates measure average risk of dying
  from a specific cancer
• number of deaths is one measure of outcome or
  impact of cancer (product of incidence and
  fatality of a given cancer)
• Fatality, (1-survival), is probability that an
  individual with cancer will die from it and is
  generally assumed to be most severe sequelae of
  disease

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• mortality rate sometimes used as convenient proxy
  measure of the risk of acquiring the disease
  (incidence) when comparing different groups,
  since it is more readily available
• BUT we need to assume equal survival or fatality
  in the populations being compared
• most of time this assumption is not correct, so
  it is safer to use mortality as measure of
  outcome rather than occurrence

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Measures of Cancer Frequency Prevalence

• NO agreed definition of prevalence of cancer
• number of persons in a defined population alive
  at a given time who have had cancer diagnosed at
  some time in past
• overall prevalence not useful for health care
  planning purposes because resource requirements
  for treating newly diagnosed patients are very
  different from those for supporting long-term
  survivors, especially since a large proportion of
  long-term survivors can be considered cured

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Measures of Cancer Frequency Prevalence

• partial prevalence limits number of patients to
  those diagnosed during fixed time in past and is
  more useful prevalence measure of cancer burden
• prevalence for cases diagnosed within 1, 3, 5
  years are likely to be of relevance to different
  stages of cancer therapy initial treatment (1
  year), clinical follow-up (3 years) and cure (5
  years)
• patients still alive 5 years after diagnosis are
  considered cured since their death rates are
  similar to general population (some exceptions,
  like breast cancer)

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Other Measurements Survival

• survival time defined as time that elapsed
  between diagnosis and death
• most basic measure of patients survival is the
  observed survival
• 5-year observed survival is percentage of
  patients alive after 5 years of follow-up from
  date of diagnosis

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Other Measurements Relative Survival

• deaths from other competing causes will lower the
  observed survival rates and preclude comparison
  between groups where probability of death in the
  general population vary
• relative survival rate can be calculated to
  avoid this problem
• relative survival rate is observed survival rate
  in a patient group divided by expected survival
  of a comparable group in the general population
  with respect to age, sex, and calendar period of
  investigation

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Other Measurements PYLL

• Potential Years of Life Lost (PYLL) measures how
  many years of normal life span are lost due to
  deaths from cancer
• takes into account both number of deaths and age
  at which death occurs
• Age-weighting function used to increase the
  relative value of adults in productive ages,
  i.e., 1 year saved for someone at 20 years old is
  valued more than for a person aged 60 years
• varying weighting functions can be given
  according to quality of these life-years

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• ?????????
• (Distribution of cancer)

(?)???? ???????,???????????????,??????????
,????????????????????????,2020?????80?,????????200
0?,??1200?,??????????????,???????????????
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• ?????,??????????????22?2000?????????1010?,?
  ?620?????????,??????????????????,?????????????,???
  ?120?,??110??

In the past 10 years, the prevelence and
mortality of cancer increased to 22.new cases
were 10.1million in 2000,and 6.2 million died.
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• ????????????????????????????????????????????
  ????????????????????50/10?????10??,???????????,???
  ??????????????,????????,??????????????

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• ?????,?????????????????1990?,???????????????
  ???,??10????,8???????????????????????????????????
  ???????????,???????????????????

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The lung cancer epidemic - UK
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The lung cancer epidemic - Canada
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Tobacco Use in the US, 1900-1999
Per capita cigarette consumption
Male lung cancer death rate
Female lung cancer death rate
Age-adjusted to 2000 US standard
population. Source Death rates US Mortality
Public Use Tapes, 1960-1999, US Mortality
Volumes, 1930-1959, National Center for Health
Statistics, Centers for Disease Control and
Prevention, 2001. Cigarette consumption Us
Department of Agriculture, 1900-1999.
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???????????? (Prevelence tendency in China)

• ??????????????20??????????,?????????????20?
  ?70???84.58/10????20??90???94.36/10?,???11.56?
• ????????????????????,??????????????????????
  ???????111.85?
• ??????69.00????1980??????????????,?1985??
  ??????,????6,?????????44???

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• ????????????????????????????
• 1.?????????????? ?????????????????????????,?????
  ??,???????????,????????????????,????????????

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• 2.??????? ?????????,?????????????????????????????
  ???
• 3.????????????????,????????????,??????????,???????
  ?,???????????????????????????????????

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????(Risk factors)

• Biological factors
• Psycho-social factors

• ?????
• ??????
• ???????
• ??????

• Genetic susceptibility factors

• Environmental physical
• and chemical factors

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?????? ????(physical factors) ????(??????)
????(chemical factors) ?? ?? ????
????????????? ???? ????
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???????(biological factors) ?? HBV HCV
HP HPV EB?? HTLV HIV ??
???? ??? ?????(schistosoma
haematobium)??? ???????(clonorchis
sinensis)????? ?????(schistosoma
japonicum)???
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?????? (Psycho-social factors)

• ?????????????
• ????,????
• ????,????
• ????,???????
• ????,????

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??????? (Genetic susceptibility factors)

• ??????
• ??????
• ?????

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???????(Prevention of Cancer)
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• ??????

(Prevention strategy)

• ?????????????
• ??????????????
• ???????
• ?????????????

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??????(preventive measures)
???? Primary prevention ???? Secondary
prevention ???? Tertiary prevention
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• ????
• ?????????
• ?????????
• ?????????
• ????

(Primary prevention)
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• ????
• ?????
• ???????????

(Secondary prevention)
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????
(Tertiary prevention)

• ?????????????????
• ????
• ?????????????
• ????????,??????????????