Possibility of lung cancer risk in indium-exposed workers: An 11-year multicenter cohort study

Abstract

Background We established a causal relationship between indium exposure and lung interstitial and emphysematous effects. Lung cancer has been clearly demonstrated in rats and mice exposed to indium phosphide and in rats exposed to indium tin oxide. However, no information is available on human indium‐related lung cancer. Methods The baseline studies were conducted on 381 indium‐exposed and 150 referent workers in 11 factories from 2003 to 2006. Items examined included indium concentration in serum (In‐S), occupational history, Krebs von den Lungen‐6 (KL‐6), chest high‐resolution computed tomography (HRCT), medical history, smoking habits, and subjective symptoms. Subjects received follow‐up health checkups, and a total of 220 indium‐exposed and 26 nonexposed workers were examined at least once with chest HRCT from 2013 to 2018. Results Four lung cancer cases were identified only in indium‐exposed workers. Two were prevalent cases and two were incident cases. The averages (range) of age (years), exposure duration (years), In‐S (μg/L), and KL‐6 (U/mL) at the baseline survey were 58 (50‐74), 1.7 (0.3‐4.8), 3.1 (0.3‐9.7), and 663 (414‐942). The mean (range) latency from initial indium exposure was 5.3 (0.4‐11) years. The HRCT findings in two incident cases were mild interstitial/emphysematous change and mild interstitial change. The standardized incidence ratio (SIR) of the incident cases was 1.89 (95%CI 0.52‐6.88). Conclusions Although the SIR was not statistically significant, there was an undeniable possibility of indium‐related lung cancer due to the short follow‐up duration being insufficient to disclose lung cancer and the small number of lung cancer cases. Further follow‐up is necessary.

Effects of indium exposure on respiratory symptoms: a retrospective cohort study in Japanese workers using health checkup data

“…This is in contrast to results from previous studies that reported an increased risk of lung cancer and interstitial pneumonia with indium exposure. In an 11-year cohort study (Nakano et al, 2019), the S-In and KL-6 levels were higher in indium-handling workers than in those who were not exposed. Other studies have also reported higher S-In, KL-6, and SP-D levels among indium-handling workers (Liu et al, 2012;Choi et al, 2013).…”

“…The first case of interstitial pneumonia that was probably related to ITO inhalation was reported in 2003 (Homma et al, 2003). Indium compounds have subsequently been demonstrated to be associated with respiratory diseases such as interstitial pneumonia and lung cancer (Chonan, Taguchi & Omae, 2007;Hamaguchi et al, 2008;Cummings et al, 2010;Cummings et al, 2012;Omae et al, 2011;Nakano et al, 2014;Nakano et al, 2015;Nakano et al, 2019). Furthermore, they are related to emphysema, alveolar proteinosis and cholesterol granuloma (Chonan et al, 2019).…”

Progress in educational program for diagnosis of occupational respiratory disease in Japan -Activity of Asian Intensive Reader of Pneumoconioses (AIR Pneumo)-

“…In Japan, indium-exposed workers were also reported to have developed pneumoconiosis due to short-term exposure. 10,11 The early stages of pneumoconiosis are interstitial pneumonia, but this inflammation then disappears, while emphysema progresses according to time. Progressive emphysema depends on the concentration of indium in the blood.…”

“…A total of 1519 new cases of diagnosed from 2001 to 2015 as pneumoconiosis indicated that pneumoconiosis tended to be accelerated among young pneumoconiosis cases with shorter duration of exposure due to the high proportion of silicosis and the insufficient occupational health management in small and medium enterprises. In Japan, indium‐exposed workers were also reported to have developed pneumoconiosis due to short‐term exposure 10,11 . The early stages of pneumoconiosis are interstitial pneumonia, but this inflammation then disappears, while emphysema progresses according to time.…”

Peer Review #1 of "Effects of indium exposure on respiratory symptoms: a retrospective cohort study in Japanese workers using health checkup data (v0.1)"

“…The first case of interstitial pneumonia that was probably related to ITO inhalation was reported in 2003 (Homma et al, 2003). Indium compounds have subsequently been demonstrated to be associated with respiratory diseases such as interstitial pneumonia and lung cancer (Chonan, Taguchi & Omae, 2007;Hamaguchi et al, 2008;Cummings et al, 2010Cummings et al, , 2012Omae et al, 2011;Nakano et al, 2014Nakano et al, , 2015Nakano et al, , 2019. Furthermore, they are related to emphysema, alveolar proteinosis and cholesterol granuloma (Chonan et al, 2019).…”