1976 dioxin accident leaves cancer legacy.

Next week in Arlington, Va., the Environmental Protection Agency will hold a workshop to review human data on the toxicity of dioxins. One sure topic for discussion will be a paper, published this week, reporting elevated cancer rates among adults near Milan, Italy. All had lived in ares downwind of a 1976 chemical accident in Seveso that resulted in the highest documented human exposures to TCDD, the most potent dioxin.

In the September EPIDEMIOLOGY, Pier Alberto Bertazzi of the University of Milan and his co-workers describe how they tracked down nearly all 20- to 74-year-olds who had resided in one of three areas through 1986: about 550 people from neighborhoods nearest the Seveso accident; roughly 4,000 from a less contaminated zone; and some 26,000 persons from areas with low and patchy dioxin tainting. They identified cases of cancer from area hospitalization records.

Few cancers turned up among people who had lived nearest the accident--even in those who had developed a disfiguring acne from their initial, heavy dioxin exposure. However, with so few people in this group and the short follow-up, this "cannot be taken as sound indication of a lack of carcinogenicity," Bertazzi's team says--especially in light of a numerically small but statistically significant excess of cancers in the next-most-exposed region.

Here, the scientists found a quintupling in the expected incidence of gallbladder and bile duct cancers among women and a more than doubling in men. They also observed about double the expected rate of cancers in blood-forming tissues, but which cancers predominated differed between men and women. An apparent excess of certain soft-tissue sarcomas showed up in both sexes, and among men, the researchers saw twice the expected rate of liver cancer.

Even in the patchy-exposure zone, Bertazzi's team observed a slightly elevated incidence of some of these cancers.

The incidence of estrogen-dependent cancers, such as those of the breast and uterus, by contrast, were strikingly lower than expected in the two most exposed zones. Similar trends, seen in dioxin-exposed rats, have been explained by TCDD's ability to decrease the number of estrogen receptors in some tissues and to interfere with the hormone's metabolism.

In an accompanying editorial, Olav Axelson of University Hospital in Linkoping, Sweden, concludes that these Seveso data "certainly represent sound epidemiology and are crucial contributions to the elucidation of the relations between dioxin-related exposures and cancer risk."