PCDDs, also known as polychlorinated dibenzo-p-dioxins, are aromatic compounds that are widely found in the environment and are difficult to degrade. PCDDs can originate from various sources, such as incineration facilities for solid waste, mills involved in pulp and paper production, fish that have been contaminated, and soil. The accumulation of PCDDs in the human body can occur through the food chain and biological enrichment, resulting in detrimental impacts on human health due to their extended half-life. Earlier research has indicated that PCDDs can lead to a range of adverse health effects in humans, such as reproductive harm (1), hypertension symptoms (2), coronary heart disease, diabetes, nervous system impairment, disruption of endocrine, immune, and reproductive systems (3), and the development of tumors (4, 5). Nevertheless, limited research has been conducted on the correlation between PCDDs and the mortality rate of cancer.

According to previous studies, occupational exposure to PCDDs can heighten the likelihood of dying from cancer (6–9). According to Li et al. (10), among workers of a municipal solid waste incinerator plant the level of PCDDs in serum due to occupational exposure is 28.0 pg/g lipid. Compared with occupational exposure, non occupational exposure has a lower level of PCDD. Nevertheless, the concentration of serum PCDDs in individuals not occupationally exposed (i.e., the general population) is 8.0 pg/g lipid for males and 9.0 pg/g lipid for females, as reported by Chen et al. in 2005. Whether relatively low PCDD exposure level can increase the risk of cancer mortality needs more research evidence. In a previous study, it was found that PCDDs were linked to an increased risk of cancer death over a period of 4.63 years. The hazard ratio (HR) and its corresponding 95% confidence interval were reported as 1.17 (0.89–1.53), but these findings did not reach statistical significance (11). The short duration of the follow-up period could be the cause of these insignificant findings. Hence, further investigation with long follow-up time is required to determine the of PCDDs non-exposure among the general population and its association with cancer mortality.

In this research, an extended period of observation was utilized to investigate the correlation between PCDDs and the death rate caused by cancer. We examine the correlation between the collective exposure levels of PCDDs and individual PCDD exposure levels, as well as the risk of cancer mortality, by employing a combination of statistical techniques that incorporate exposure models and single exposure models.

The study included a total of 2,992 participants, comprising of 1,461 males and 1,531 females (Table 2). The mean follow-up time was 138.3 months. In total, 1,002 people died, of whom 230 died from cancer. The racial distribution did not differ between males and females (p = 0.835). In women, the occurrence rate of PIR below 1 was greater compared to men, with a p-value less than 0.001. Men had a higher level of smoking exposure, with 36.5% of them having a cotinine frequency greater than 10, compared to 23.5% in women. BMI classification between men and women also has a different distribution. The male vigorous group accounted for 52.9% more than the female group, which had a significant difference (p < 0.001), among the exercise variables. The proportion of males in the drinking group was significantly higher than that of females, with 57.4 and 40.6%, respectively (p < 0.001).

In the examination of overall death rate, we discovered that there was no notable distinction in the correlation between the five PCDDs and overall death rate in the findings of model 1 (Table 3). In the second model, there was a correlation observed between a rise of 1 log unit in 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin and all-cause mortality (HR = 1.79, 95% CI 1.22, 2.53, p = 0.003). There was no significant correlation found between the remaining four PCDDs and all-cause mortality. In our examination of cancer death rates, we discovered that there was no notable distinction in the correlation between the five PCDDs and cancer mortality in model 1. In the second model, it was discovered that a rise of 1 log unit in the presence of 1,2,3,4,6,7,8-heptachlorodibenzofuran led to an increased likelihood of cancer-related deaths (HR = 1.98, 95% CI 1.05, 3.43, p = 0.034). The remaining four PCDDs were not statistically associated with cancer mortality.

Upon analyzing the quartiles of PCDDs, it was determined that there was no heightened risk associated with all-cause mortality for any of the five PCDDs (refer to Table 4). In the findings of the association analysis concerning cancer mortality (Table 5), it was noted that the HR for the uppermost quantile of 1,2,3,4,6,7,8-heptachlorodibenzofuran, in comparison to the lowest quantile, was 2.00 (1.06, 3.79). The HR for the highest quantile of 1,2,3,4,6,7,8-heptachlorodibenzofuran, compared to the lowest quantile, was 2.23 (1.13, 4.40). The other four PCDDs were not statistically associated with cancer mortality risk.

In addition, we examined the correlation between cancer mortality risk and the dosage of 1,2,3,4,6,7,8-heptachlorodibenzofuran using an RCS model (Figure 1). The findings indicated a direct correlation between the compound 1,2,3,4,6,7,8-heptachlorodibenzofuran and the risk of cancer-related deaths, with a P_linear value of 0.044. The above two variables did not exhibit a nonlinear relationship, with a P_non-linear value of 0.262. Furthermore, we carried out a sensitivity analysis as well. By either eliminating the covariate PIR variable or enhancing the covariate education level, the findings remained consistent, indicating the robustness of our results (Tables 6, 7).

The findings of the current research revealed that higher levels of exposure to 1,2,3,4,6,7,8-heptachlorodibenzofuran, a form of PCDD, were linked to an elevated likelihood of cancer fatality. The risk of cancer mortality increased by 90% with the addition of each extra 1,2,3,4,6,7,8-heptachlorodibenzofuran. In addition, 1,2,3,4,6,7,8-heptachlorodibenzofuran was linearly associated with cancer mortality.

In the general population, our research discovered a correlation between exposure to PCDD and the likelihood of cancer-related deaths. In previous studies, the cancer mortality of environmental chemicals in occupational populations has been widely studied. Occupationally exposed individuals have a higher concentration of chemicals in their bodies compared to the general population. According to Leroyer et al.’s study (13), there was no observed link between cancer mortality and the exposure to various chemicals in the workplace. In the study conducted by Zhivin and colleagues (14), the mortality risk of kidney and bladder cancer due to exposure to hydrazine and other fuels in the population exposed to these substances at work was observed, however, no statistically significant distinction was found. The findings from these occupational exposure categories did not establish a connection between environmental chemicals and the risk of death, indicating that not all occupational exposures to environmental chemicals are linked to mortality risk. There is chemical specificity between environmental chemicals and mortality risk. An elevated amount of dioxin exposure is linked to a rise in mortality rates from bladder cancer (15). Furthermore, a meta-analysis indicated that the exposure to dioxin was linked to a heightened likelihood of cancer fatality (16). Furthermore, being exposed to PCDDs in the workplace can lead to a rise in cancer-related deaths (7, 17). These findings additionally demonstrate that there exists a distinct chemical specificity between environmental substances and the risk of mortality. Previous research in the field of mortality risk among the overall populace has indicated a strong correlation between the element cadmium and tumor fatality (18, 19). It is suggested that PCDD may also have similar risks. In contrast, Lin et al. discovered that PCDD did not have any connection with the likelihood of tumor death among the overall populace (11). Upon enlarging the sample size and extending the duration of follow-up, we discovered a correlation between PCDD and a heightened likelihood of tumor fatality. Different results may be discovered with a substantial sample size and an extended duration of follow-up, as recommended.

This study found that nonoccupational exposure to PCDD can cause an increase in tumor mortality, which may have certain public health significance. Currently, numerous elements contribute to the heightened likelihood of tumor fatality, encompassing cadmium of metallic nature (20), PM_2.5 particles (21), and phthalate substances (22). Nevertheless, these factors alone are insufficient to account for tumor mortality, implying that unidentified environmental substances impact tumor mortality. The findings of our research indicate that even a small amount of PCDD can lead to a higher likelihood of tumor-related deaths, making it the first study to establish this connection. Reducing the exposure to PCDD may potentially decrease the risk of tumor mortality. PCDD can be found in various sources that humans are exposed to, such as emissions from industries, outdated pesticide supplies, heating in households, recycling of electronic waste, and the incineration and combustion of household waste (23). To decrease human PCDD exposure, another approach is to minimize the origin of PCDD exposure. Hence, minimizing the contact with chemicals might lead to a decrease in the presence of chemicals within the body. Hence, considering public health, implementing drug intervention and minimizing chemical contact are two approaches to decrease the level of chemicals in the body, which could potentially lower the chances of tumor fatality among the population.

This study has the following advantages. In the initial investigation using the cohort study approach, we discovered, for the very first instance, that among individuals not occupationally exposed, there exists a direct association between combined exposure to PCDDs and tumor mortality. Furthermore, we observed a noteworthy 90% rise in the likelihood of risk. Furthermore, our research revealed a strong correlation between tumor mortality and the presence of 1,2,3,4,6,7,8-heptachlorodibenzofuran in PCDD. This study also has limitations. Firstly, in this study, the origin of PCDD exposure cannot be disclosed initially. Clarifying the exposure source of PCDD can reduce its harm. Secondly, the PCDD exposure level in this study was based on a single determination, which could introduce bias. Therefore, it is necessary to conduct multiple determinations in future studies to establish a reliable and consistent exposure level. Thirdly, varying individuals may possess distinct PCDD metabolism, potentially resulting in diverse health consequences stemming from identical levels of PCDD exposure. This requires adding variables affecting the metabolic level of PCDD in subsequent studies to reduce such bias. Fourthly, it remains uncertain if the findings of this research can be universally applied worldwide. People in different regions have different exposure levels to PCDDs and different life spans. Hence, additional areas and larger sample sizes should be examined. Fifthly, occupational exposure is one of the important reasons affecting PCDD, but due to the lack of occupational information data in NHANES, we can not adjust this variable in the statistical analysis of the present study. This may affect our results, which needs attention in the follow-up study. Sixthly, this study was conducted by sampling, and there was also sampling bias existing. In the discussion part, we gave the biological evidence of potential PCDD causing tumor, which may reduce such bias, but the sampling bias should not be ignored in the future study. Seventhly, previous studies have found that PCDD residues can be partially detected in eggs, mussels, milk and cheese produced around the areas where PCDD industry comes from (24–27). Therefore, the intake of eggs, mussels, milk and cheese produced may be a confounding factor of PCDD, which needs to be collected as a covariate in subsequent studies. Eighthly, dietary exposure is the main source of non occupational exposure to human to exposure to PCDD. Mussels, as a kind of seafood, and PCDD is accumulated in it (25). Eating seafood can reduce the total cause of death, although there is no statistical difference (28). These evidences suggest that the dietary exposure, such as consumption of mussels, may lead to biased results.

This research revealed that PCDD may elevate the likelihood of cancer-related deaths among the overall populace.

The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author/s.

The consent form was signed by the survey participants, and the participants consented to storing specimens of their blood for future research. The CDC/NCHS Ethics Review Board approved the NHANES study and gave approval for public dissemination.

LZ: Writing – original draft. XZ: Data curation, Writing – review & editing. ZG: Formal analysis, Writing – original draft. CZ: Validation, Writing – review & editing. DQ: Methodology, Writing – review & editing. QY: Conceptualization, Supervision, Writing – original draft.