Cancer Causes & Control

, Volume 25, Issue 4, pp 499–506 | Cite as

Loss of a parent and the risk of cancer in early life: a nationwide cohort study

  • Beatrice Kennedy
  • Unnur Valdimarsdóttir
  • Karin Sundström
  • Pär Sparén
  • Mats Lambe
  • Katja Fall
  • Fang Fang
Original Paper



While early-life exposure to stress has been associated with subsequent psychiatric and cardiovascular morbidity, little is known regarding its potential role in cancer development. We hypothesized that severe emotional stress, such as the loss of a parent through death during childhood, may increase the risk of cancer in early life.


Based on the Swedish Multi-Generation Register, we identified a cohort of 4,219,691 individuals who had both parents identifiable in the same register and followed the cohort from birth to the age of 40 years between 1961 and 2006. Through information retrieved from the Swedish Causes of Death and Cancer Registers, we ascertained death among the parents and cancer diagnosis among the cohort individuals. We used Poisson regression to calculate the relative risks (RRs) and 95 % confidence intervals (CIs).


Parental death was not associated with total cancer risk. However, parental death during childhood was associated with a higher risk of human papillomavirus (HPV) infection-related cancers (RR 1.4; 95 % CI 1.2–1.7), and loss during early adulthood (>18 years) entailed a higher risk of cancers of the stomach (RR 1.8; 95 % CI 1.3–2.6), lung (RR 1.7; 95 % CI 1.1–2.4), rectum (RR 1.4; 95 % CI 1.0–2.0), and breast (RR 1.1; 95 % CI 1.0–1.3). A significant association was observed for pancreatic cancer for both loss during childhood (RR 2.6; 95 % CI 1.6–4.2) and afterward (RR 2.8; 95 % CI 1.9–4.3).


Our results suggest that severe psychological stress in early life may be associated with premature development of certain malignancies, particularly cancers related to smoking and HPV infection.


Sweden/epidemiology Cohort studies Psychological stress Neoplasms/epidemiology/etiology HPV/infection Risk 


  1. 1.
    Garssen B (2004) Psychological factors and cancer development: evidence after 30 years of research. Clin Psychol Rev 24(3):315–338. doi:10.1016/j.cpr.2004.01.002 PubMedCrossRefGoogle Scholar
  2. 2.
    McGee R (1999) Does stress cause cancer? There’s no good evidence of a relation between stressful events and cancer. BMJ 319(7216):1015–1016PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Cassileth BR (1996) Stress and the development of breast cancer: a persistent and popular link despite contrary evidence. Cancer 77(6):1015–1016PubMedCrossRefGoogle Scholar
  4. 4.
    Petticrew M, Fraser JM, Regan MF (1999) Adverse life-events and risk of breast cancer: a meta-analysis. Br J Health Psychol 4:1–17. doi:10.1348/135910799168434 CrossRefGoogle Scholar
  5. 5.
    Duijts SF, Zeegers MP, Borne BV (2003) The association between stressful life events and breast cancer risk: a meta-analysis. Int J Cancer 107(6):1023–1029. doi:10.1002/ijc.11504 PubMedCrossRefGoogle Scholar
  6. 6.
    Ross K (2008) Mapping pathways from stress to cancer progression. J Natl Cancer Inst 100 (13):914–915, 917. doi:10.1093/jnci/djn229 Google Scholar
  7. 7.
    Lutgendorf SK, Sood AK, Anderson B, McGinn S, Maiseri H, Dao M, Sorosky JI, De Geest K, Ritchie J, Lubaroff DM (2005) Social support, psychological distress, and natural killer cell activity in ovarian cancer. J Clin Oncol 23(28):7105–7113. doi:10.1200/jco.2005.10.015 PubMedCrossRefGoogle Scholar
  8. 8.
    Costanzo ES, Sood AK, Lutgendorf SK (2011) Biobehavioral influences on cancer progression. Immunol Allergy Clin North Am 31(1):109–132. doi:10.1016/j.iac.2010.09.001 PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Hermes GL, Delgado B, Tretiakova M, Cavigelli SA, Krausz T, Conzen SD, McClintock MK (2009) Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors. Proc Natl Acad Sci USA 106(52):22393–22398. doi:10.1073/pnas.0910753106 PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    McLaughlin KA, Conron KJ, Koenen KC, Gilman SE (2010) Childhood adversity, adult stressful life events, and risk of past-year psychiatric disorder: a test of the stress sensitization hypothesis in a population-based sample of adults. Psychol Med 40(10):1647–1658. doi:10.1017/s0033291709992121 PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Stein DJ, Scott K, Haro Abad JM, Aguilar-Gaxiola S, Alonso J, Angermeyer M, Demytteneare K, de Girolamo G, Iwata N, Posada-Villa J, Kovess V, Lara C, Ormel J, Kessler RC, Von Korff M (2010) Early childhood adversity and later hypertension: data from the World Mental Health Survey. Ann Clin Psychiatry 22(1):19–28PubMedCentralPubMedGoogle Scholar
  12. 12.
    Momen NC, Olsen J, Gissler M, Cnattingius S, Li J (2013) Early life bereavement and childhood cancer: a nationwide follow-up study in two countries. BMJ Open 3 (5). doi:10.1136/bmjopen-2013-002864
  13. 13.
    Li J, Vestergaard M, Obel C, Cnattingus S, Gissler M, Ahrensberg J, Olsen J (2012) Antenatal maternal bereavement and childhood cancer in the offspring: a population-based cohort study in 6 million children. Br J Cancer 107(3):544–548. doi:10.1038/bjc.2012.288 PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Fang F, Fall K, Sparen P, Adami HO, Valdimarsdottir HB, Lambe M, Valdimarsdottir U (2011) Risk of infection-related cancers after the loss of a child: a follow-up study in Sweden. Cancer Res 71(1):116–122. doi:10.1158/0008-5472.can-10-0470 PubMedCrossRefGoogle Scholar
  15. 15.
    Barlow L, Westergren K, Holmberg L, Talback M (2009) The completeness of the Swedish Cancer Register: a sample survey for year 1998. Acta Oncol 48(1):27–33. doi:10.1080/02841860802247664 PubMedCrossRefGoogle Scholar
  16. 16.
    Grulich AE, Jin F, Conway EL, Stein AN, Hocking J (2010) Cancers attributable to human papillomavirus infection. Sex Health 7(3):244–252. doi:10.1071/sh10020 PubMedCrossRefGoogle Scholar
  17. 17.
    Anda RF, Williamson DF, Escobedo LG, Mast EE, Giovino GA, Remington PL (1990) Depression and the dynamics of smoking. A national perspective. JAMA 264(12):1541–1545PubMedCrossRefGoogle Scholar
  18. 18.
    Li J, Johansen C, Hansen D, Olsen J (2002) Cancer incidence in parents who lost a child: a nationwide study in Denmark. Cancer 95(10):2237–2242. doi:10.1002/cncr.10943 PubMedCrossRefGoogle Scholar
  19. 19.
    Levav I, Kohn R, Iscovich J, Abramson JH, Tsai WY, Vigdorovich D (2000) Cancer incidence and survival following bereavement. Am J Public Health 90(10):1601–1607PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Keinan-Boker L, Vin-Raviv N, Liphshitz I, Linn S, Barchana M (2009) Cancer incidence in Israeli Jewish survivors of World War II. J Natl Cancer Inst 101(21):1489–1500. doi:10.1093/jnci/djp327 PubMedCrossRefGoogle Scholar
  21. 21.
    Shi M, Du L, Liu D, Qian L, Hu M, Yu M, Yang Z, Zhao M, Chen C, Guo L, Wang L, Song L, Ma Y, Guo N (2012) Glucocorticoid regulation of a novel HPV-E6-p53-miR-145 pathway modulates invasion and therapy resistance of cervical cancer cells. J Pathol 228(2):148–157. doi:10.1002/path.3997 PubMedCrossRefGoogle Scholar
  22. 22.
    Antoni MH, Lutgendorf SK, Cole SW, Dhabhar FS, Sephton SE, McDonald PG, Stefanek M, Sood AK (2006) The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer 6(3):240–248. doi:10.1038/nrc1820 PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Bosch FX, Burchell AN, Schiffman M, Giuliano AR, de Sanjose S, Bruni L, Tortolero-Luna G, Kjaer SK, Munoz N (2008) Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine 26(Suppl 10):K1–16. doi:10.1016/j.vaccine.2008.05.064 PubMedCrossRefGoogle Scholar
  24. 24.
    Plummer M, Peto J, Franceschi S (2012) Time since first sexual intercourse and the risk of cervical cancer. Int J Cancer 130(11):2638–2644. doi:10.1002/ijc.26250 PubMedCrossRefGoogle Scholar
  25. 25.
    Dowdney L (2000) Childhood bereavement following parental death. J Child Psychol Psychiatry 41(7):819–830PubMedCrossRefGoogle Scholar
  26. 26.
    Brent D, Melhem N, Donohoe MB, Walker M (2009) The incidence and course of depression in bereaved youth 21 months after the loss of a parent to suicide, accident, or sudden natural death. Am J Psychiatry 166(7):786–794. doi:10.1176/appi.ajp.2009.08081244 PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Hipwell A, Stepp S, Chung T, Durand V, Keenan K (2012) Growth in alcohol use as a developmental predictor of adolescent girls’ sexual risk-taking. Prev Sci 13(2):118–128. doi:10.1007/s11121-011-0260-3 PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Brookmeyer KA, Henrich CC (2009) Disentangling adolescent pathways of sexual risk taking. J Prim Prev 30(6):677–696. doi:10.1007/s10935-009-0196-6 PubMedCrossRefGoogle Scholar
  29. 29.
    Wilson K, Asbridge M, Kisely S, Langille D (2010) Associations of risk of depression with sexual risk taking among adolescents in Nova Scotia high schools. Can J Psychiatry 55(9):577–585PubMedGoogle Scholar
  30. 30.
    Muniz-Cohen M, Melhem NM, Brent DA (2010) Health risk behaviors in parentally bereaved youth. Arch Pediatr Adolesc Med 164(7):621–624. doi:10.1001/archpediatrics.2010.101 PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Fang CY, Miller SM, Bovbjerg DH, Bergman C, Edelson MI, Rosenblum NG, Bove BA, Godwin AK, Campbell DE, Douglas SD (2008) Perceived stress is associated with impaired T-cell response to HPV16 in women with cervical dysplasia. Ann Behav Med 35(1):87–96. doi:10.1007/s12160-007-9007-6 PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Raimondi S, Maisonneuve P, Lohr JM, Lowenfels AB (2007) Early onset pancreatic cancer: evidence of a major role for smoking and genetic factors. Cancer Epidemiol Biomarkers Prev 16(9):1894–1897. doi:10.1158/1055-9965.epi-07-0341 PubMedCrossRefGoogle Scholar
  33. 33.
    Al-Wadei HA, Plummer HK 3rd, Ullah MF, Unger B, Brody JR, Schuller HM (2012) Social stress promotes and gamma-aminobutyric acid inhibits tumor growth in mouse models of non-small cell lung cancer. Cancer Prev Res (Phila) 5(2):189–196. doi:10.1158/1940-6207.capr-11-0177 CrossRefGoogle Scholar
  34. 34.
    Schuller HM, Al-Wadei HA, Ullah MF, Plummer HK 3rd (2012) Regulation of pancreatic cancer by neuropsychological stress responses: a novel target for intervention. Carcinogenesis 33(1):191–196. doi:10.1093/carcin/bgr251 PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Huang J, Valdimarsdottir U, Fall K, Ye W, Fang F (2013) Pancreatic cancer risk after loss of a child: a register-based study in Sweden during 1991–2009. Am J Epidemiol 178(4):582–589. doi:10.1093/aje/kwt045 PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Beatrice Kennedy
    • 1
  • Unnur Valdimarsdóttir
    • 2
  • Karin Sundström
    • 3
  • Pär Sparén
    • 3
  • Mats Lambe
    • 3
    • 4
  • Katja Fall
    • 1
    • 2
  • Fang Fang
    • 3
  1. 1.Clinical Epidemiology and Biostatistics Unit, School of Health and Medical SciencesÖrebro University and Örebro University HospitalÖrebroSweden
  2. 2.Faculty of Medicine, Centre of Public Health Sciences, School of Health SciencesUniversity of IcelandReykjavíkIceland
  3. 3.Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
  4. 4.Regional Cancer CentreUppsala University HospitalUppsalaSweden

Personalised recommendations