1. What happened in Seveso, Italy?
In 1976, an explosion occurred in a chemical facility, releasing large amounts of dioxin over the city of Seveso, Italy. Soon after the explosion, blood specimens from women who lived in Seveso were taken and stored.

This study was based on 981 women, whose age ranged from infants to age 40 at the time of the explosion. In this study, the blood dioxin concentrations of exposed females were evaluated to see if there could be a link to the development of breast cancer in the 40 years that followed. The study found that women who had greater exposure to dioxin were more likely to develop breast cancer than women with less exposure to dioxin. Compared to those with 10 times less exposure, the women with the higher exposure were over twice as likely to develop breast cancer after exposure.

2. Details on the study
It is important to note that is study is different than the type of study mentioned in other sections of this website because it involves a high amount of exposure to an environmental contaminant due to an industrial accident. Other sections in this website refer to exposures that are higher than normal, but usually less than the amount that would be expected in an industrial accident such as the explosion in Seveso.

This study is also unique for several reasons. It does not contain an unexposed group; instead, it compares women with different levels of exposure to dioxin. Furthermore, it uses a biomarker, which is the concentration of dioxin in blood samples from study participants. Researchers examined the relationship between the amount of dioxin in the participant's blood sample and the likelihood of developing breast cancer.

However, there is a limitation in this study's use of a biomarker. Dioxin is a persistent organic pollutant. This means that it stays in the environment for a long time and that it increases in concentration as it is passed up the food chain. In this study, researchers did not measure dioxin that accumulates in the blood in the time after the initial blood sample. It is likely that dioxin persisted in the environment of Seveso. If a woman continued to live in this area after the explosion, she was most likely exposed to more dioxin over time. Unfortunately, this study was not designed to measure this continued exposure.

3. Why was a health study appropriate in Seveso, Italy?
Basic Question 1:
Is there contamination?
Yes, extremely high levels of dioxin were found in residential neighborhoods in Seveso, Italy
Basic Question 2:
Did people come into contact with the contamination?
People were exposed. Soon after the explosion blood samples were taken from women who lived in Seveso at the time of the explosion. These samples were analyzed to determine the concentration of dioxin in their blood, which revealed how much dioxin exposure each woman had received. Using blood samples to measure levels of dioxin exposure is an example of an exposure biomarker.
Basic Question 3:
Could the contaminant cause the health outcome?
Yes, dioxin is a known human carcinogen. Previous studies have shown that dioxin exposure is associated with an increase in deaths from all types of cancer. However, previous studies have not shown that this increase in deaths is due to a specific cancer.
Basic Question 4:
How much were people exposed to?
The amount of exposure was high enough that it could possibly cause health effects. The explosion created some of the highest exposures known to a human residential population. Some of the more highly exposed persons had exposures a thousand times higher than most urban exposure sources of dioxins.
Basic Question 5:
Is the timing right?
Yes, the amount of time was long enough for the disease to show up in most people who participated in the study. However, there could possibly still be cases occurring in the future among study participants; for example, in the case of infants or persons who were very young at the time of the explosion.
Advanced Question 1:
Can you find the right people who you need to study?
Yes, researchers found women who lived in Seveso at the time of the explosion, thus were exposed to dioxin. They had blood samples taken from them soon after the explosion.
Advanced Question 2:
Can you group people correctly into exposed and unexposed groups?
Exposure can be very accurately classified. The stored blood specimens taken soon after the explosion showed how much dioxin each woman had been exposed to. However, one limitation of this exposure classification is that it does not measure dioxin levels after the blood sample was taken. Thus, any exposure to dioxin in the years following the explosion was not measured and not taken into account in this analysis.
Advanced Question 3:
Can you correctly group people who have a health outcome and those who do not?
Yes. Each participant was asked if they had breast cancer. If a woman reported she had breast cancer, then her medical records were reviewed to verify this information. This information could also be verified using the cancer registry in Italy.
Advanced Question 4:
Are there other causes of the health outcome that we might be overlooking?
Yes, other factors could cause breast cancer, but these factors were considered during the statistical analysis. The study researchers interviewed participants about other factors, such as age at first pregnancy, family history of breast cancer, and smoking.
One limitation of this study was that researchers did not ask about other possible sources of dioxin exposure. There are many different sources of exposure to dioxin, such as ingesting certain meats and dairy products, breathing gases released from burning or industrial processes, and performing job tasks resulting in the release of dioxins.
Advanced Question 5:
Is the study likely to find a link between exposure and illness?
Yes. Researchers probably decided on acceptable levels for level of significance and study power by:
  • Determining what number of exposed and unexposed people were needed for large enough sample size
  • Estimating the expected number of breast cancer cases in the unexposed population during the study time period
  • Predicting the number of breast cancer cases among subjects divided into different groups during the study time period. Each group reflects a different range of dioxin levels in the subjects' blood.
Researchers also probably considered that:
  • Breast cancer is one of the more common cancers. Having a high background rate of disease like this one increases study power.
  • This level of dioxin exposure was expected to cause a notable increase in breast cancers. If the increase in cancer was not expected to be very high, it would be difficult to tell whether the increase in cancer was actually due to dioxin exposure.
Before proceeding with the health study, researchers needed to determine if there was a good chance that their study would be able to find an increase in cancer due to the air contamination from the facility.
4. Summary table
exposure Dioxin released into air due to chemical facility explosion in 1976
health outcome Breast cancer
type of study Cohort study
questions this study seeks to answer Did women exposed to higher levels of dioxin show higher risk of developing breast cancer than women exposed to lower levels of dioxin?
Does exposure to dioxin increase the risk of developing breast cancer?
target population Women who were exposed to dioxin from a factory explosion in Seveso, Italy and who had their blood sampled soon after the explosion
data collected and methodology Blood samples from women were taken after the explosion (1976-1981) Women were asked if they had breast cancer
Medical records were reviewed to verify cases
data analysis Statistical test to investigate a possible relationship between high levels of dioxin in the blood sample and risk of developing cancer
of this study
Used biomarker to assess different amounts of dioxin exposure among participants
Because participants were exposed to such high levels of dioxin, there was an increased likelihood of observable health effects
of this study
No measurement of dioxin exposure after a single blood draw soon after exposure
Researchers did not ask about other possible exposures to dioxin besides the explosion