Original Investigation
May 17, 2023
Association of Trauma With Long-Term Risk of Death and Immune-Mediated or Cancer Disease in Same-Sex Twins
Trine O. Eskesen, Martin Sillesen, Jacob Krabbe Pedersen, et al
JAMA Surg. 2023;158(7):738-745. doi:10.1001/jamasurg.2023.1560
Question Is moderate to severe trauma associated with long-term increased risk of death or immune-mediated or cancer disease?
Findings In this nationwide co-twin cohort study of same-sex twins discordant on trauma, twins exposed to moderate to severe trauma had a significantly increased risk of death or immune-mediated or cancer disease for more than 20 years after the trauma when compared with their co-twin who had not been exposed to trauma.
Meaning Moderate to severe trauma may increase the risk of death and immune-mediated or cancer disease not only close to the trauma but continues to be a risk factor several years after the injury.
Abstract
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.
