Den 3. stressforsknings konference 2006

1. 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

2. 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

3. Cause Personality Depression Mood Schizophrenia Major life events Psychoactive drugs Religious belief Effect Social life Psychological well-being Divorce Income Work Psychiatric diseases Depression Psychoactive drugs Screening for fam. BC Prognosis Home visit Education Rehabilitation Internet groups Current research activities Prevention Smoking in adolescence

4. The epidemiological approach in psychosocial oncology focus on: Background • Risk factors • Psychosocial effects • Psychosocial factors as prognostic factors • Prevention

5. Background

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

7. Background Risk factors

8. 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

9. 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

10. Background Basic principles/problems Exposure by ’mind’ factor Exposure assessment Cancer diagnosis Time

11. Risk factors • Major life events • Depression • Personality

12. 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

13. Didier Bar - the Loreto Village with the Vesuvio in eruption, Rome, private collection

14. Major life events

15. Etiology considerations • Latency • Duration • Initiation • Promotion • Timing

16. 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)

17. 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)

18. Duration Personality traits • Schapiro I et al. Personality and risk for cancer. American Journal of Epidemiology2001; 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

19. 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

20. Initiation or Promotion (?) Initiator establish gene defect Promotor increase rate of malignant cell division Cancer diagnosis Time

21. Timing When is the vulnerable exposure window (?) Birth Cancer diagnosis Time

22. 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)

23. Etiology considerations • Latency • Duration • Initiation • Promotion • Timing

24. 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 Epidemiology2002; 155: 1088-95

25. Louis N. Kenton (1865–1947)

26. Tobacco-related cancer risk

27. 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

28. 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

29. Edvard Munch(1863-1944)

30. 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

31. The Cohort Invited 7734 Excluded 676 (12%) Participants 5812 (75%) Study population 5136 (88%)

32. 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

33. Cox proportional hazard analyses included information of: Analyses • Age • Sex • Personality measurement • Marital status • Social class • Alcohol consumption • Tobacco smoking • Body mass index

34. Adjusted risk of cancer

35. 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

36. 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

37. 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.

38. Discussion Biological mechanism Immunefunction Cancer Mind

39. 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.

40. Impaired immune system Conclusion I A. The cancer-prone mind model Pathophysiological processes Cancer Mind B. The mind-health behaviour model Pathophysiological processes Cancer Mind Healthbehaviour

41. Conclusion I Stress does not cause cancer IARC 4: The agent (mixture) is probably not carcinogenic to humans

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

43. 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

44. Adriaen Brouwer (Flemish, 1606?–1638)

45. Information and contact christof@cancer.dk www.cancer.dk