Histopathologic Analysis of Lung Cancer Incidence Associated with Radon Exposure among Ontario Uranium Miners.

Avinash Ramkissoon,Paul Villeneuve,Paul Demers,Colin Berriault,Minh Do,Garthika Navaranjan

doi:10.3390/ijerph15112413

Abstract

Although radon is a well-established contributor to lung cancer mortality among uranium miners, the effects of radon decay products on different histopathologies of lung carcinoma are not well established. Using a retrospective cohort design, this study aims to examine the risks of lung cancer by histological subtypes associated with exposure to radon decay products among the Ontario Uranium Miners cohort. Cases were stratified by histological groups, and associated risks were estimated for cumulative radon exposure after adjustment for attained age and calendar period. Between 1969 and 2005, 1274 incident cases of primary lung cancer were identified. Of these, 1256 diagnoses (99%) contained information on histology. Squamous cell carcinoma was most common (31%), followed by adenocarcinoma (20%), large cells (18%), small cell lung carcinoma (14%), and other or unspecified cell types (17%). Of the histological sub-groups, small cell lung carcinoma had the strongest association with cumulative radon exposure; compared to the reference group (<1 cumulative working level months (WLM)), the highest exposure category (>60 cumulative WLM) had a relative risk (RR) of 2.76 (95% CI: 1.67–4.57). Adenocarcinoma had the lowest risk and was not significantly associated with exposure to radon decay products (RR = 1.49, 95% CI: 0.96–2.31). An increasing, linear trend in relative risk was noted with increasing cumulative WLM across small cell, squamous cell, and large cell lung carcinomas (Ptrend < 0.05). Similarly, the excess relative risk (ERR) per WLM was highest for small cell lung carcinoma (ERR/WLM = 0.15, p < 0.01), followed by squamous cell carcinoma (ERR/WLM = 0.12, p < 0.01). Non-statistically significant excess risk was observed for adenocarcinoma (ERR/WLM = 0.004, p = 0.07). Our analysis of the Ontario Uranium Miners cohort data shows differences in the magnitude of the risks across four histological subtypes of lung carcinoma; the strongest association was noted for small cell lung carcinoma, followed by squamous cell, large cell, and lastly adenocarcinoma, which showed no significant associations with exposure to radon decay products.

Highlights

Epithelial cells that are the front line barrier to alpha radiation would receive the majority of the dose, and would be at highest risk of tumorigenesis. These findings suggest that the radon decay process can more readily initiate DNA damage of epithelial tissues, such as squamous and small cell carcinomas through direct irradiation compared to adenocarcinoma [25]
Future work with these data includes investigating the inverse dose rate effect in this cohort, stratified by histologic subtype; the same cumulative dose protracted over a longer time may result in certain histologic subtypes more frequently than others, and further investigation is warranted. This analysis demonstrates the capacity for histologic analyses for other incident cancers; the issue of statistical power may limit the ability to stratify less common cancers. This is the first comprehensive study of lung cancer risk associated with exposure to radon decay products evaluated by histological subtypes among a cohort of Ontario Uranium Miners
Based on our analysis of the Ontario Uranium Miners cohort file, we found that the incidence of lung cancer was strongly associated with occupational radon exposure

Summary

Introduction

Excess risks for lung cancer mortality associated with radon exposure have been consistently demonstrated in uranium miner cohorts in the United States [5,6], France [7,8,9], Czechoslovakia [10,11,12], Germany [13,14,15], and other non-uranium mining cohorts [16,17]. Consistent with the international literature, our recent update of the Ontario Uranium Miners cohort found an excess lung cancer risk, which persisted many years after leaving the mining industry [18]. Studies on the risk of lung cancer associated with radon exposure have historically been focused on mortality rather than incident cases. There are four main histological sub-classifications: small cell carcinoma (SmCC), squamous cell carcinoma (SqCC), adenocarcinoma (AdC), and large cell carcinoma (LCC)

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