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Review Paper
Beyond cohort versus case-control: the primacy of exposure assessment over study design in occupational cancer epidemiology
Yangwoo Kim, Dong-Uk Park
Epidemiol Health. 2026;48:e2026026.   Published online June 8, 2026
DOI: https://doi.org/10.4178/epih.e2026026
  • 1,030 View
  • 29 Download
AbstractAbstract AbstractSummary PDF
Abstract
In occupational cancer epidemiology, prospective cohort studies are conventionally ranked above case-control studies. However, exposure assessment quality—central to occupational risk estimation—receives less methodological attention than study design. This review argues that divergent cohort and case-control risk estimates reflect exposure assessment limitations rather than study design. Three findings support this. First, variance decomposition demonstrates that group-level exposure assignment attenuates effect estimates by a reliability ratio approaching zero as within-worker variability becomes dominant. Second, Berkson error in job-exposure matrices, combined with model non-linearity, biases estimates toward the null. Third, the healthy worker effect, immortal time bias, and left truncation compound misclassification and shift cohort estimates further toward the null. Two case studies illustrate this pattern. For night shift work and breast cancer, the case-control odds ratio (OR) of 1.34 contrasted with the cohort relative risk (RR) of 0.98; at 30 years’ cumulative exposure, these estimates were 1.88 and 1.13. For welding fumes and lung cancer, the pooled cohort RR of 1.29 contrasted with a case-control OR of 1.87; Sørensen’s cohort, using individual breathing-zone measurements, recovered a hazard rate ratio of 2.34 at the highest cumulative exposure. Thus, an occupational cancer study’s inferential value depends on its exposure assessment method rather than its design label. Group-level assignment attenuates effect estimates and may compromise etiological inference regardless of nominal design. Individual exposure reconstruction—through occupational interviews, industrial hygiene assessment, or personal monitoring—supports precise dose-response estimation. Quality assessment tools and meta-analyses should stratify evidence by exposure assessment method rather than design label.
Summary
Korean summary
본 연구에서는 직업성 암 역학 연구에서 코호트 연구, 환자-대조군 연구 등 역학 연구 설계보다 노출평가의 질이 효과 추정의 정확성을 좌우한다고 주장하고자 한다. 직업명이나 직무노출매트릭스와 같은 집단수준 노출 할당은 측정오차와 구조적 편향이 결합되어 연관성을 영가설 방향으로 약화시킬 수 있는 반면, 개인수준에서의 노출 측정과 그에 따른 노출 재구성은 용량-반응 관계를 더 잘 포착할 수 있다. 따라서 직업성 암 역학 연구에서 코호트와 환자-대조군 연구의 근거를 평가하거나 메타분석 연구를 진행할 때에는 역학 연구 설계를 다루는 것에만 머무르지 않고 노출평가 방법과 그 정밀도에 따라 층화하는 연구 방법론의 정립이 필요하다.
Key Message
For occupational carcinogens with long latency, group-level exposure assignment in prospective cohort studies systemati- cally attenuates risk estimates. Regulatory and quality-assessment frameworks should evaluate studies by the precision of their exposure information—distinguishing individual-level reconstruction from group-level assignment—rather than by their nominal design label. Null findings from cohorts relying on job-title classification warrant caution due to this systematic attenuation.
Systematic Review
Confounding and the healthy worker survivor effect in studies of medical radiation workers: a systematic review of methodological approaches
Eun Jung Park, Kyoungyeol Yuk, Jaeho Jeong, Won Jin Lee
Epidemiol Health. 2026;48:e2026009.   Published online February 4, 2026
DOI: https://doi.org/10.4178/epih.e2026009
  • 5,805 View
  • 118 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
Confounding and the healthy worker survivor effect (HWSE) represent major methodological challenges in epidemiology, particularly in studies of low-dose exposures, where effect sizes are small and risk estimates can be readily distorted by bias. This systematic review aimed to summarize the methods used to adjust for confounding and the HWSE in studies of medical radiation workers. We systematically searched PubMed and Embase for studies of medical radiation workers from inception through June 30, 2025. Studies reporting excess risk estimates for any health outcomes associated with occupational radiation exposure were included. Study selection followed the PECO (Population, Exposure, Comparator, Outcome) criteria, and data were synthesized descriptively. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in PROSPERO (CRD42024589851). Sixteen eligible studies from 3 countries were identified, all of which were rated as high quality. To control for confounding, regression was used in all studies, followed by stratification (62.5%) and restriction (18.8%). Age, sex, and birth year were adjusted for in all models, with smoking being the next most frequently controlled variable. To mitigate the HWSE, only a single approach, adjustment for employment characteristics, was identified, and it was applied in 3 studies (18.8%). No other approaches, including restriction or g-methods, were employed. Although confounding is generally addressed using conventional analytical approaches, the HWSE has rarely been considered in studies of medical radiation workers. More comprehensive strategies that explicitly account for the HWSE are needed to improve the validity of risk estimates, particularly in low-dose occupational studies.
Summary
Korean summary
교란 및 건강근로자 생존효과는 역학 연구에서 해결해야 할 중요한 과제이며, 특히 저노출 연구에서는 효과 크기가 상대적으로 작아 이러한 영향에 더욱 취약하다. 연구 결과, 의료방사선종사자 연구에서 교란은 회귀분석 및 층화와 같은 전통적인 방법을 통해 적절히 보정되고 있지만, 건강근로자 생존효과를 줄이기 위한 방법은 대부분의 연구에서 적용되지 않고 있다. 향후 역학 연구에서는 보다 정확한 위험도 평가를 위해 건강근로자 생존효과를 줄이기 위한 다양한 방법의 적용이 필요하다.
Key Message
Confounding and the healthy worker survivor effect (HWSE) are major methodological challenges in epidemiology, particu- larly in studies involving low-dose exposure. Although confounding is generally considered to have only a limited impact in occupational epidemiology, a variety of analytical methods have nonetheless been applied to control it. In contrast, the HWSE, despite being widely recognized as a major source of bias, has rarely been mitigated in practice. More comprehensive strat- egies that explicitly account for the HWSE are needed to improve the validity of risk estimates.

Citations

Citations to this article as recorded by  
  • Cardiovascular composite events and the healthy worker effect among noise-exposed workers: a retrospective cohort study
    Jiahui Liu, Qi Li, Jiamin Liu
    Frontiers in Public Health.2026;[Epub]     CrossRef
Original Article
Correlation Study on Clinical Laboratory Findings with Occupational Exposure to Low Dose Ionizing Radiation in Nuclear Workers in Korea.
Young Khi Lim, Keun Young Yoo
Korean J Epidemiol. 2001;23(2):8-18.
  • 9,923 View
  • 18 Download
AbstractAbstract PDF
Abstract
PURPOSE
Even though atomic energy and radioisotope had been made for a peaceful purpose, some of the public do't feel safe possibly due to potential exposure to ionizing radiation. While health effects of high level radiation are almost deterministic, the stochastic effects of the 'low-dose radiation' have not come to a correct conclusion. This correlation study was conducted to assess the health effect due to potential exposure th low-dose radiation in the nuclear power plants workers in Korea.
METHODS
The study subjects was selected among the nuclear workers. Among those who attend the epidemiologic survey for screening of any malignancies done by the study group of Seoul National University Hospital during 1992-1993, 1) those who had undertaken both the physical examination with clinical laboratory tests and the direct interview with questionnaire, 2) male workers, and 3) those with record on radiation dosimetry as well as employment records in the company. Correlation analysis with Pearson's correlation coefficients and quantitative analysis with normal ranges of various tests were done by the PC-SAS for window.
RESULTS
Total cumulative radiation doses was relatively low, ranging 1 mSv at the lowest to 391 mSv at the highest. Moreover, mostly 68.7% of the subjects was within lower limit of total cumulative doses under 10 mSv. Among the clinical laboratory test, statistical significant correlation was see in hemoglobin(HGB), creatinine(CRE), and carcinoembryonic antigen(CEA).
CONCLUSION
This study concluded that health effect of occupational exposure to low-dose ionizing radiation is minimal or, if any, extremely lower than expected in the nuclear power plants workers in Korea. Major limitation of this study is that the healthy worker effect could not excluded. A large-scale prospective epidemiologic study on the relationship between radiation exposure and health hazard is needed to draw a more valid conclusion.
Summary

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