World War II was raging in Europe and it would be 11 months until the United States entered the war, when Cancer Research published its first issue in January 1941. As we celebrate the 75th Anniversary of Cancer Research, we pause to admire the authors of those volume issues who were conducting their research amidst one the of the most devastating armed and genocidal conflicts in human history; we are also gratified to contemplate the enduring role of science in human development, persevering in the face of profound aggression and impending tragedy. The author of the paper we honor in this article, Nathan Mantel, served in the U.S. Army between 1942 and 46 before he was recruited to the NCI as a biostatistician.
Our task is to evaluate a landmark article by Nathan Mantel (1) published in 1967 that outlined a methodologic breakthrough to evaluate whether disease occurrences were related to exposures by their spatiotemporal pattern of clusters. During the previous three decades, there had been keen interest in discerning which environmental exposures might be responsible for the increasing incidence of cancers such as hematologic cancers, hepatocellular carcinoma, bladder, and breast cancer. This is a problem that captured the attention of the world following the Chernobyl nuclear accident and domestically in the United States through the popular accounts of famous cancer clusters associated with industrial waste in Woburn, MA and Toms River, NJ, both told in depth of detail and insight in two nonfiction books (2, 3). The methodology employed to discern whether these well-known cases and many other instances of suspected environmental contamination are true clusters, is based largely on Mantel’s 1967 Cancer Research article.