Association of Trauma With Long-Term Risk of Death and Immune-Mediated or Cancer Disease in Same-Sex Twins

JAMA Surg. 2023 Jul 1;158(7):738-745. doi: 10.1001/jamasurg.2023.1560.


Importance: Immediate consequences of trauma include a rapid and immense activation of the immune system, whereas long-term outcomes include premature death, physical disability, and reduced workability.

Objective: To investigate if moderate to severe trauma is associated with long-term increased risk of death or immune-mediated or cancer disease.

Design, setting, and participants: This registry-based, matched, co-twin control cohort study linked the Danish Twin Registry and the Danish National Patient Registry to identify twin pairs in which 1 twin had been exposed to severe trauma and the other twin had not from 1994 to 2018. The co-twin control design allowed for matching on genetic and environmental factors shared within twin pairs.

Exposure: Twin pairs were included if 1 twin had been exposed to moderate to severe trauma and the other twin had not (ie, co-twin). Only twin pairs where both twins were alive 6 months after the trauma event were included.

Main outcome and measure: Twin pairs were followed up from 6 months after trauma until 1 twin experienced the primary composite outcome of death or 1 of 24 predefined immune-mediated or cancer diseases or end of follow-up. Cox proportional hazards regression was used for intrapair analyses of the association between trauma and the primary outcome.

Results: A total of 3776 twin pairs were included, and 2290 (61%) were disease free prior to outcome analysis and were eligible for the analysis of the primary outcome. The median (IQR) age was 36.4 (25.7-50.2) years. The median (IQR) follow-up time was 8.6 (3.8-14.5) years. Overall, 1268 twin pairs (55%) reached the primary outcome; the twin exposed to trauma was first to experience the outcome in 724 pairs (32%), whereas the co-twin was first in 544 pairs (24%). The hazard ratio for reaching the composite outcome was 1.33 (95% CI, 1.19-1.49) for twins exposed to trauma. Analyses of death or immune-mediated or cancer disease as separate outcomes provided hazard ratios of 1.91 (95% CI, 1.68-2.18) and 1.28 (95% CI, 1.14-1.44), respectively.

Conclusion and relevance: In this study, twins exposed to moderate to severe trauma had significantly increased risk of death or immune-mediated or cancer disease several years after trauma compared with their co-twins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cohort Studies
  • Humans
  • Middle Aged
  • Neoplasms*
  • Proportional Hazards Models
  • Twins, Monozygotic*