Increased liver and lupus mortalities in 24-year follow-up of the Taiwanese people highly exposed to polychlorinated biphenyls and dibenzofurans

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Abstract

Background

A follow-up study was designed to compare the 24-year overall and disease-specific mortality in Yucheng people who were highly exposed to polychlorinated biphenyls/dibenzofurans (PCBs/PCDFs) to that in the background population in Taiwan. In 1979, the Yucheng (oil-disease in Chinese) incident occurred in central Taiwan involving approximately 2000 victims due to ingestion of rice oil contaminated with PCBs/PCDFs. Long-term follow-up of these people has been continued for 24 years.

Methods

Standardized mortality ratios were calculated using the Taiwan population as comparison group. Overall and disease-specific mortality was compared between Yucheng and background populations.

Results

Mortality from chronic liver disease and cirrhoses was increased in the Yucheng men, but not in women, in the early period after exposure. Cancer mortality was not increased in the Yucheng population up to 24 years after exposure. SLE in females was highly increased in the later period after PCB/PCDF exposure. Mortality from disease in any other organ system was not significantly different between Yucheng and background populations.

Conclusions

The study provided a long-term mortality picture after the Taiwanese PCB/PCDF exposure incident. In addition to re-confirming the increase in liver mortality, we found high mortality of SLE among exposed population. This finding highlights the importance of further investigating the immunological effects associated with PCB/PCDF exposure.

Introduction

Polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants found in many environmental media, as well as biological samples from wildlife and humans (Anderson, 1989). PCBs became recognized as potentially harmful environmental contaminants in the 1970s, and their use and manufacture were prohibited in many countries.

Since dioxin-like chemicals were strong animal carcinogens, mortality investigations on PCBs and dioxin-like chemicals have relatively emphasized on cancer outcomes until recent years. Published follow-up studies of workers exposed to PCBs through inhalational or dermal routes showed inconsistent results with elevated mortality rates for brain cancer (Sinks et al., 1992, Kimbrough et al., 2003, Ruder et al., 2006), gastrointestinal cancer (Bertazzi et al., 1987, Tironi et al., 1996, Kimbrough et al., 2003, Prince et al., 2006), malignant melanoma (Sinks et al., 1992, Kimbrough et al., 2003, Ruder et al., 2006), cancer of the biliary tract, liver and gallbladder (Brown and Jones, 1981, Brown, 1987, Kimbrough et al., 2003, Gustavsson et al., 1986, Gustavsson and Hogstedt, 1997, Prince et al., 2006), cancer of the hematopoietic system (Bertazzi et al., 1987, Kimbrough et al., 2003, Gustavsson et al., 1986, Gustavsson and Hogstedt, 1997) and prostate cancer (Prince et al., 2006, Charles et al., 2003). Cardiovascular diseases, diabetes, and autoimmune diseases were not found increased in most of the above studies.

Follow-up of occupational cohorts exposure to PCDD/PCDF and Ranch Hand cohort exposed to Agent Orange contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) showed increased cancer mortality (Fingerhut et al., 1991, Steenland et al., 1999, Flesch-Janys et al., 1998, Hooiveld et al., 1998, Ott and Zober, 1996, Ketchum and Michalek, 2005). Significant cause-specific cancer mortalities were documented including rectum cancer (Flesch-Janys et al., 1998), larynx cancer (Steenland et al., 1999), bladder cancer (Steenland et al., 1999), respiratory (Fingerhut et al., 1991, Flesch-Janys et al., 1998, Hooiveld et al., 1998, Ott and Zober, 1996), soft tissue sarcoma (Fingerhut et al., 1991, Saracci et al., 1991), and lymphatic and hematopoietic cancer (Flesch-Janys et al., 1998, Steenland et al., 1999). Although Seveso cohort exposed to TCDD failed to exhibit significant increase of all cancer mortality (Bertazzi et al., 2001), lymphatic and hematopoeitic cancers were found increased, as well as cancers in rectum and lung among men. In the Japanese Yusho (“oil-disease” in Japanese) population exposed to PCBs and PCDFs, increased liver cancer mortality in both sexes and lung cancer mortality in men were reported at the 15-year follow-up. Mortality of circulatory diseases was increased in Ranch Hand cohort (Ketchum and Michalek, 2005). Deaths due to diabetes and chronic obstructive pulmonary disease were found increased in Seveso cohort (Bertazzi et al., 2001). Mortality caused by chronic liver disease was found increased in Japanese Yusho cohort at a non-statistically significant level (Ikeda et al., 1987).

In 1979, over 2000 people in central Taiwan ingested cooking rice oil contaminated with PCBs/PCDFs (Hsu et al., 1985). The victims were estimated to consume an average of 1 g of PCBs and 3.8 mg of PCDFs totally during an average of 9 months of exposure to the contaminated oil (Lan et al., 1981). The structure of PCDFs is similar to TCDD, a known potent carcinogen (Voogt and Brinkman, 1989). Such consumption resulted in median serum levels at the order of 10–40 times higher than background for PCBs and 10,000 times higher for penta-CDF (Svensson et al., 1991). By 1983, a Yucheng (“oil-disease” in Chinese) registry was set up and maintained by the Taiwan Provincial Department of Health including 1991 directly exposed subjects, and 70 children exposed in utero (Hsu et al., 1985).

We began following he Yucheng cohort and studied mortality related to exposure in 1992. Increased mortality due to chronic liver disease and cirrhosis was found 13 years after exposure, but not increase in cancer mortality (Yu et al., 1997). This study extends the follow-up period and examines the mortality in the Yucheng cohort 24 years after exposure to PCBs and PCDFs. Since we have more person-years of follow-up, we are able to stratify the Yucheng population into males and females, and also looked into different periods after the exposure, i.e., 0–7, 8–15, and 16–23 years.

Section snippets

Materials and methods

The follow-up study of mortality status has been approved by the Institutional Review Board of The National Cheng Kung University. We obtained the Yucheng Registry previously (Yu et al., 1997). Among the 1991 in the list, 154 did not appear in the registration office records, or did not have an address, and thus could not be traced further. These individuals were excluded from the first study of mortality in 1992 (Yu et al., 1997). In this study, we were able to obtain the checking system for

Subjects

A total of 1823 Yucheng subjects with 43,319 person-years are at risk from the time of first exposure to PCBs to date of death or the last date of each study period. The age, gender, and vital status distribution of the exposed subjects are shown in Table 1. Two hundred fifteen subjects had died between January 1, 1980 and December 31, 2003.

SMR, overall and by gender

Table 2 shows results for the all cause and cause-specific mortality. All cause mortality was not different from that in the Taiwan general population.

Discussion

In this study, long-term follow-up of mortality among the population exposed to PCBs/PCDFs after Taiwan “Yucheng” incident was reported. Mortality of chronic liver disease and cirrhoses was found increased in early period after exposure in exposed men, but not in women. The rare autoimmune disease-SLE was highly increased in women during both later periods (8–15, and 16–23 years) after PCBs/PCDFs exposure as compared to the Taiwan general population. Cancer mortality was not increased in the

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