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      Review for Retrospective Exposure Assessment Methods Used in Epidemiologic Cancer Risk Studies of Semiconductor Workers: Limitations and Recommendations

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          Abstract

          This article aims to provide a systematic review of the exposure assessment methods used to assign wafer fabrication (fab) workers in epidemiologic cohort studies of mortality from all causes and various cancers. Epidemiologic and exposure–assessment studies of silicon wafer fab operations in the semiconductor industry were collected through an extensive literature review of articles reported until 2017. The studies found various outcomes possibly linked to fab operations, but a clear association with the chemicals in the process was not found, possibly because of exposure assessment methodology. No study used a tiered assessment approach to identify similar exposure groups that incorporated manufacturing era, facility, fab environment, operation, job and level of exposure to individual hazardous agents. Further epidemiologic studies of fab workers are warranted with more refined exposure assessment methods incorporating both operation and job title and hazardous agents to examine the associations with cancer risk or mortality.

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          Most cited references17

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          Mortality among semiconductor and storage device-manufacturing workers.

          We evaluated mortality during 1965 to 1999 among 126,836 workers at two semiconductor facilities and one storage device facility. We compared employees' cause-specific mortality rates with general population rates and examined mortality patterns by facility, duration of employment, time since first employment, and work activity. Employees had lower-than-expected mortality overall (6579 observed deaths, standardized mortality ratio [SMR] = 65; 95% confidence interval [CI] = 64-67), for all cancers combined (2159 observed, SMR = 78, 95% CI = 75-81) and for other major diseases. Central nervous system cancer was associated with process equipment maintenance at one of the semiconductor facilities (10 observed, SMR = 247, 95% CI = 118-454). Prostate cancer was associated with facilities/laboratories at the storage device facility (18 observed, SMR = 198, (5% CI = 117-313). Further evaluation of workplace exposures or independent investigations of similar occupational groups may clarify the interpretation of associations observed in this study.
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            Cancer incidence and cancer mortality in a cohort of UK semiconductor workers, 1970-2002.

            To examine cancer risks in a cohort of workers employed in the manufacture of semiconductors. The mortality (1970-2002) and cancer morbidity (1971-2001) experienced by a cohort of 1807 male and female workforce employees from a semiconductor factory in the West Midlands (UK) have been investigated. Standardized mortality ratios (SMRs) and standardized registration ratios (SRRs) were used to assess mortality and morbidity, respectively. Overall mortality was close to expectation in males [SMR 99, 95% (confidence interval) CI 79-122] and significantly below expectation in females (SMR 74, 95% CI 65-85). Incidence of all sites of cancer was somewhat elevated in males (SRR 130, 95% CI 95-173) but close to expectation in females (SRR 94, 95% CI 82-109). There were significant deficits of deaths from cancer of the oesophagus in males and females combined and from cancer of the breast in females. Significantly elevated SRRs were found in males for cancer of the rectum [Observed (Obs) 6, SRR 284, 95% CI 104-619], in females for cancer of the pancreas (Obs 10, SRR 226, 95% CI 108-415) and malignant melanoma (Obs 11, SRR 221, 95% CI 110-396) and in males and females combined for cancer of the rectum (Obs 19, SRR 199, 95% CI 120-310) and malignant melanoma (Obs 12, SRR 217, 95% CI 112-379). Detailed work history data were unavailable for analysis. The finding of excess morbidity was not mirrored in the corresponding mortality findings. The study found elevated morbidity for a number of cancer sites that may be unconnected with occupation. Elimination of all possible occupational causes will, however, require more detailed analyses of cancer risks in relation to exposure histories.
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              Cancer Mortality and Incidence in Korean Semiconductor Workers

              Objectives The purpose of this study was to evaluate cancer risks in the Korean semiconductor industry. Methods A retrospective cohort study was performed in eight semiconductor factories between 1998 and 2008. The number of subjects was 113,443 for mortality and 108,443 for incidence. Standardized mortality ratios (SMR) and standardized incidence ratios (SIR) were calculated. Results The SMR of leukemia was 0.39 (95% Confidence Interval 0.08-1.14) in males (2 cases) and 1.37 (0.55-2.81) in females (7 cases). The SMR of non-Hodgkin's lymphoma (NHL) was 1.33 (0.43-3.09, 5 cases) in males and 2.5 (0.68-6.40, 4 cases) in females. The SIR of leukemia was 0.69 (0.30-1.37, 8 cases) in males and 1.28 (0.61-2.36, 10 cases) in females. The SIR of NHL in females was 2.31 (1.23-3.95, 13 cases) and that of thyroid cancer in males was 2.11 (1.49-2.89, 38 cases). The excess incidence of NHL was significant in female assembly operators [SIR=3.15 (1.02-7.36, 5 cases)], but not significant in fabrication workers. The SIR of NHL in the group working for 1-5 years was higher than the SIR of NHL for those working for more than five years. The excess incidence of male thyroid cancer was observed in both office and manufacturing workers. Conclusion There was no significant increase of leukemia in the Korean semiconductor industry. However, the incidence of NHL in females and thyroid cancer in males were significantly increased even though there was no definite association between work and those diseases in subgroup analysis according to work duration. This result should be interpreted cautiously, because the majority of the cohort was young and the number of cases was small.
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                Author and article information

                Contributors
                Journal
                Saf Health Work
                Saf Health Work
                Safety and Health at Work
                Occupational Safety and Health Research Institute
                2093-7911
                2093-7997
                07 June 2018
                September 2018
                07 June 2018
                : 9
                : 3
                : 249-256
                Affiliations
                [1]Department of Environmental Health, Korea National Open University, Seoul, Republic of Korea
                Author notes
                []Corresponding author. Department of Environmental Health, Korea National Open University, 86 Daehak-ro, Seoul 03087, Republic of Korea. pdw545@ 123456gmail.com
                Article
                S2093-7911(18)30008-8
                10.1016/j.shaw.2018.05.005
                6129997
                f1245c07-8697-47d6-82db-73cd2495a3d8
                © 2018 The Author

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 9 January 2018
                : 14 March 2018
                : 23 May 2018
                Categories
                Review Article

                Occupational & Environmental medicine
                chemical,epidemiologic study,fab operation,retrospective exposure assessment,semiconductor industry

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