Den 3. stressforsknings konference 2006

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Den 3. stressforsknings konference 2006

• Mind and cancer
• Christoffer Johansen, M.D., Ph.D., DrMedSci.
• Head, Department of Psychosocial Cancer Research
• Institute of Cancer Epidemiology
• Danish Cancer Society

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Background

• The Department of Psychosocial Cancer Research
  (2001) utilise the epidemiological approach and
  combine register-based research with clinical
  studies in an effort to study the association
  between psychological factors, social factors and
  cancer
• The department combines various methodological
  approaches to the subject and employs a range of
  persons educated from anthropology to statistics

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Current research activities
Prevention
Smoking in adolescence
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The epidemiological approach in psychosocial
oncology focus on
Background

• Risk factors
• Psychosocial effects
• Psychosocial factors as prognostic factors
• Prevention

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Background
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Background
The central paradigm

• Mind is an independent risk factor as well as an
  independent prognostic factor in cancer
• How is it possible to investigate this paradigm
  ??

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Background
Risk factors
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Background

• Numerous case-control studies, cross-sectional
  studies and retrospective follow-up studies have
  demonstrated the central paradigm but only few
  acknowledge the limitations of these methods
  especially when dealing with our mind

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Background

• This retrospective tradition has some inborn
  methodological problems
• Recall bias among cases
• Exposure assessment by interview
• Exposure assessment after diagnosis
• Limited adjustment for biological factors

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Background
Basic principles/problems
Exposure by mind factor
Exposure assessment
Cancer diagnosis
Time
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Risk factors

• Major life events
• Depression
• Personality

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Major life events
Johansen C. Olsen JH. No effect of
psychological stress on cancer incidence or
mortality from nonmalignant diseases. British
Journal of Cancer 1997 75 144-148
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Didier Bar - the Loreto Village with the Vesuvio
in eruption, Rome, private collection
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Major life events
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Etiology considerations

• Latency
• Duration
• Initiation
• Promotion
• Timing

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Latency

• The exposure to the diagnosis of cancer in a
  child and risk for cancer in parents (Johansen
  Olsen JH. No effect of psychological stress on
  cancer incidence or mortality from nonmalignant
  diseases. British Journal of Cancer 1997 75(1)
  144-148)
• The death of a child and risk for cancer in
  parents (Li J et al. Cancer incidence in
  parents who lost a child a nationwide study in
  Denmark. Cancer 2002 95 2237 2242)
• The exposure to various stressful life-events
  (Bergelt C et al. Stressful life-events and risk
  for cancer. European Journal of Cancer, in press
  2006)

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Latency

• The diagnosis of scizophrenia in a child and risk
  for cancer in parents. (Dalton SO et al.
  Cancer incidence in parents who experience a
  child with schizophrenia a major life event
  study in Denmark. British Journal of Cancer 2004
  90 1364 66)
• Hospital admission for depression and subsequent
  risk for cancer (Dalton SO et al. Depression
  and risk for cancer a register-based study of
  patients hospitalized with affective disorders,
  Denmark, 1969-93. American Journal of
  Epidemiology 2002 155 1088-95)

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Duration
Personality traits

• Schapiro I et al. Personality and risk for
  cancer. American Journal of Epidemiology 2001
  153 757 763.
• Schapiro I et al. Psychic vulnerability and the
  associated risk of cancer. Cancer 2002 94 3299
  3306.
• Hansen PE et al. Personality traits, health
  behavior and risk for cancer A prospective study
  of a Swedish twins cohort. Cancer 2005 103 1082
  1091.
• Bergelt C et al. Vital exhaustion and risk for
  cancer a prosepctive cohort study on the
  association between depressive feelings, fatigue
  and risk for cancer. Cancer 2005 104 1288 -
  1295

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Duration

• A large prospective study of daily job strain
  among 26 936 women in the American Nurses Health
  study (Achat 2000)
• Perceived stress of daily activities in a Finnish
  cohort of 10 519 women (Lillberg 2001)
• No increased risk for breast cancer

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Initiation or Promotion (?)
Initiator establish gene defect
Promotor increase rate of malignant cell
division
Cancer diagnosis
Time
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Timing
When is the vulnerable exposure window (?)
Cancer diagnosis
Birth
Time
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Timing

• We currently study the risk of cervical dysplasia
  among young women exposed the death of one or two
  parents during childhood and adolescence
  (Magtengaard 2006)
• We also study the risk for cancer after the death
  of spouse, divorce or separation (Ross 2007)

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Etiology considerations

• Latency
• Duration
• Initiation
• Promotion
• Timing

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Depression

• S Oksbjerg Dalton, L Mellemkjær,
• JH Olsen and C Johansen, , PB Mortensen.
  Depression and cancer risk A register-based
  study of patients hospitalized with affective
  disorders, Denmark, 1969-93
• American Journal of Epidemiology 2002 155
  1088-95

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Louis N. Kenton (18651947)
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Tobacco-related cancer risk
Total Total First year of follow-up First year of follow-up ? 1 years of follow-up ? 1 years of follow-up
Obs SIR Obs SIR Obs SIR
Reactive depression 2075 1.13 184 1.62 1891 1.10
Tobacco related1 663 1.41 58 2.03 605 1.37
Non-tobacco-related 1412 1.03 126 1.48 1286 1.00
Dysthymia 2285 1.18 118 1.32 2167 1.17
Tobacco related1 714 1.56 30 1.58 684 1.56
Non-tobacco-related 1571 1.06 88 1.25 1486 1.06
95 CI excludes 1.00 1Cancers of the buccal cavity, larynx, lung, esophagus, pancreas, kidney and urinary bladder 95 CI excludes 1.00 1Cancers of the buccal cavity, larynx, lung, esophagus, pancreas, kidney and urinary bladder 95 CI excludes 1.00 1Cancers of the buccal cavity, larynx, lung, esophagus, pancreas, kidney and urinary bladder 95 CI excludes 1.00 1Cancers of the buccal cavity, larynx, lung, esophagus, pancreas, kidney and urinary bladder 95 CI excludes 1.00 1Cancers of the buccal cavity, larynx, lung, esophagus, pancreas, kidney and urinary bladder 95 CI excludes 1.00 1Cancers of the buccal cavity, larynx, lung, esophagus, pancreas, kidney and urinary bladder 95 CI excludes 1.00 1Cancers of the buccal cavity, larynx, lung, esophagus, pancreas, kidney and urinary bladder 95 CI excludes 1.00 1Cancers of the buccal cavity, larynx, lung, esophagus, pancreas, kidney and urinary bladder 95 CI excludes 1.00 1Cancers of the buccal cavity, larynx, lung, esophagus, pancreas, kidney and urinary bladder
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Conclusions

• This study gives no further support to the
  hypotheses that depression increases the risk for
  cancer
• The increased risk observed in this study can
• probably be ascribed to increased smoking

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Personality
Schapiro I, Falgaard Nielsen L, Jørgensen T,
Boesen E, Johansen C. Psychic vulnerability and
the associated risk of cancer. Cancer 2002 94
3299-3306
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Edvard Munch (1863-1944)
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A number of studies have reported that
personality influence the risk of cancer
Hagnell 1966, Huggan 1968, Abse et al. 1974,
Dattore et al.1980, Kirkcaldy Kobylinska 1987,
Scherg 1987, Grossarth-Maticek et al. 1988,
Quander-Blaznik 1991
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The Cohort
Invited 7734
Participants 5812 (75)
Excluded 676 (12)
Study population 5136 (88)
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Psychic vulnerability

• A reaction readiness defined by a low threshold
  of being influenced and a risk of inexpedient
  reactions in social interaction or in a
  psychosomatic direction

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Cox proportional hazard analyses included
information of
Analyses

• Age
• Sex
• Personality measurement
• Marital status
• Social class
• Alcohol consumption
• Tobacco smoking
• Body mass index

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Adjusted risk of cancer
Variable Multivariate adjusted HR 95 CI
Vulnerability 1.16 0.85-1.57
Current smokers 1.39 1.05-1.83
Alcohol consumption gt 14 units of alcohol per week 1.50 1.05-2.15
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Discussion

• Exposure information (mind factor) from
  administrative sources versus based on personal
  interviews or questionnaires
• Lack of confounder information (biology)
• Recall bias in case control studies a serious
  problem

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Discussion

• The association between the mind factor and
  behaviour
• Smoking, alcohol and diet are self-medications in
  order to cope with major life events, depression
  and personality
• Policies to prevent smoking and alcohol
  consumption may focus more on well defined groups
  at risk for developing these behaviours

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Discussion

• Do stress prevent cancer ?
• Nielsen et al. BMJ 2005 High endogenous
  concentrations of oestrogen are a known risk
  factor for breast cancer, and impairment of
  oestrogen synthesis induced by chronic stress may
  explain a lower incidence of breast cancer in
  women with high stress.
• Impairment of normal body function should not,
  however, be considered a healthy response, and
  the cumulative health consequences of stress may
  be disadvantageous.

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Discussion

• Biological mechanism

Immunefunction
Cancer
Mind
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Discussion

• Contrary to the mind cancer hypothesis we did
  not identify an increased risk for immune system
  related cancers such as leukemia, lymphoma and
  liver cancer in any of the studies published so
  far.
• In addition we did not observe an increased risk
  for hormone related cancers such as breast cancer
  or ovary cancer.

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Conclusion I

A.

The cancer-prone mind model



Pathophysiological processes

Mind
Cancer





B.

The mind-health behaviour model


Pathophysiological processes




Cancer
Mind
Health behaviour



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Conclusion I

• Stress does not cause cancer
• IARC 4
• The agent (mixture) is probably not carcinogenic
  to humans

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Conclusion II
Policies to prevent smoking and alcohol
consumption may focus more on well defined groups
at risk for developing these behaviours
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Conclusion III

• Social inequality is probably the new risk
  factor for risk behaviour and thus increased risk
  for certain lifestyle associated cancer types
  will be more prevalent in lower social classes
  compared to higher social classes
• Social class determines survival

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Adriaen Brouwer (Flemish, 1606?1638)
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Information and contact

• christof_at_cancer.dk
• www.cancer.dk