This study measured DL_PCB and PCDD/DF using pooled serum from general population. PCDD/DFs in blood showed a significant positive association with T2DM and thyroid cancer development, but no significant association with DL_PCB was observed.
In 2016, International Agency for Research on Cancer (IARC) upgraded the classification of the PCBs to Category 1 carcinogenic to humans from the previous Category 2A classification on the basis of sufficient evidence of carcinogenicity in humans and animals [39, 40]. However, no evidence of a relationship between PCB exposure and the risk of malignant melanoma has been identified in the latest meta-analysis , and reviews of epidemiological studies on PCB exposure and cancer risk were inconsistent for other cancers . Our result that DL_PCBs are not associated with cancer is similar to that of recently reported studies [41, 42].
Although previous studies have found an association between PCB levels and T2DM in women, our results are inconsistent with reports from other studies suggesting that PCBs are positively associated with T2DM in women. [43, 44]. However, the PCBs used in previously reported studies are a combination of DL-PCBs and non-dioxin-PCBs. In this study, however, there was included only DL-PCBs.
To the best of our knowledge, no case-control studies have yet been conducted to establish an association between dioxins and thyroid cancer. However, recent in vitro studies using immortal mouse cells have shown that TCDD exposure regulates the script of an endothelial carcinogen network thought to affect thyroid carcinoma . TCDD can interfere with the activity and metabolism of thyroid hormones through various processes, including binding to protein transport of thyroid hormone , direct damage to the thyroid gland, and activation of thyroid metabolizing enzymes . Previous reported epidemiological studies have found significantly increasing trends in mean TSH with TCDD category . Having a high TSH level within the normal range is an independent risk factor for DTC, and may contribute to the initiation of thyroid carcinogenesis [49, 50]. These mechanisms can support the association between blood PCDD/DFs and thyroid cancer risks identified in our study.
Dioxins have been identified as endocrine disruptors of the environment, but epidemiology studies of their effect on diabetes found inconsistent results [7, 11, 18, 51]. In particular, this association is found in women and not in men [12, 44], which is similar to the results confirmed in our study. Several assumptions can explain this gender difference. First, men have lower levels of exposure and a higher prevalence of smoking, which stimulates the aryl hydrocarbon receptor related to the increased excretion of PCBs . Second, women have a higher proportion of fat, resulting in these lipophilic compounds being stored longer. Third, women have higher estrogen levels and PCDFs. Certain PCBs can cause gene expression of CYP1A1 and CYP1B1 [53, 54], which catalyze estradiol A-ring hydroxylation to from 4-hydroxyl estradiol of catechol estrogen that can produce free radicals. It is understood that free radicals induce elevated oxidative stress related to diabetes .
Despite the fact that the results are similar to those of previous studies, there are some limitations in our study. First, we were unable to control the confounding variables such as exercise habits, food consumption, alcohol status, smoking status, and socioeconomic status. In this study, several blood samples were used to make pooled samples. In the case of a continuous variable, the mean value of the characters constituting the sample was used. And categorical variables were not included in this study. However, we used BMI, which is strongly associated with physical activity patterns, waist circumference, and dietary consumption, and may thus be considered a proxy indicator for such variables. Second, as an exposure measure, we used a 1-time dioxins level measurement in the blood and did not have accumulated exposure dose information. However, we had the strength of measuring PCDD/DFs and DL-PCB concentrations directly within the Korean population to collect exposure data. Also, since the half-life of PCDD/Fs in the serum can last for seven years or longer [51, 55] and over that duration, the causes of environmental exposure remained constant, we could conclude that the dioxins level in a given participant has remained similar over the years. This study also has strengths. This analysis is the first study between blood concentration of dioxin and health outcomes in general populations with low dose exposure. Thus, it has been evaluated for the health impact of dioxin on the general population. And the analysis showed the possibility of studying dioxins that needs a large amount of blood for detection using a pooled sample. Furthermore, this research will serve as a base for future studies, which identifies dioxin's health impact mechanism.