Abstract 6474: Stress-related sick leave and subsequent cancer risk: A Swedish national register study of 516 678 cancer cases
Authors: Lu Sai San Moon , Hadrévi Jenny , Järvholm Lisbeth Slunga , Späth Florentin , Palmqvist Richard , Olsson Tommy , Harlid Sophia , van Guelpen Bethany 
Published: June 2023

Abstract
Background: Despite previous studies investigating psychological stress in relation to cancer risk, no consensus has been reached as to whether stress is a modifiable risk factor for cancer. This study aims to investigate whether sick leave due to psychological stress can affect the risk of developing cancer.
Method: This is a matched case-control study using Swedish nation-wide register data (study period 2005-2018). The main exposure is stress-related sick leave defined as registered sick leave due to psychological stress with the diagnosis codes of F43 (International Classification of Diseases codes: ICD) and its subclassifications and hereafter referred to as stress leave. For each primary cancer case (except non-melanoma skin cancer), up to five cancer-free controls were matched based on sex, age and county. Conditional logistic regression, conditioned on matching factors and adjusting for socioeconomic factors, was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). For subgroup analyses by specific tumor sites, Bonferroni-corrected significance level of 0.002 (alpha value divided by the number of tumor sites = 0.05/24) was also applied.
Results: The study comprised 516 678 cancer cases and 2 357 433 matched controls. Stress leave of any duration, was associated with a modestly increased risk of cancer, with the highest risk observed for 1-30 days of leave, vs no leave during follow-up (adjusted OR 1.05, 95% CI 1.02-1.09). In subgroup analyses by tumor sites, stress leave was associated with an increased risk of prostate cancer (adjusted OR for &gt;90 days vs no stress leave 1.10, 95% CI 1.01-1.20) and cervix cancer (adjusted OR&gt;90 days vs no leave 1.11, 95% CI 1.05-1.17). For lung cancer, an inverse risk relationship was found (adjusted OR&gt;90 days vs no leave 0.88, 95% CI 0.77-0.99). For other tumor sites, associations were generally null or had wide confidence intervals. After applying a Bonferroni-corrected significance level, the association was still significant for cervical cancer. Further examination by sex, specific types of psychological stress and cancer groups based on established etiology (tobacco use, obesity, alcohol consumption and gastric hyperacidity) showed a clear exposure-response trend in men and pronounced associations for exhaustion disorder (ICD code: F43.8A) and tobacco-related cancers. In a post-hoc analysis, the association for other HPV-related cancers was similar to that for cervical cancer but not statistically significant.
Conclusion: In this register study covering the entire Swedish population, we found that stress-related sick leave was associated with modestly higher risk of cancer, particularly the risk of cervical cancer. Potential higher risk of prostate cancer and lower risk of lung cancer were observed, though these associations were not statistically significant after controlling for multiple testing.
Citation Format: Sai San Moon Lu, Jenny Hadrévi, Lisbeth Slunga Järvholm, Florentin Späth, Richard Palmqvist, Tommy Olsson, Sophia Harlid, Bethany van Guelpen. Stress-related sick leave and subsequent cancer risk: A Swedish national register study of 516 678 cancer cases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6474.