Kenneth L Abbott, MD, FACP  |  3/31/2022

As Ye Sew…

I continue our annual focus on colorectal cancer by writing about a little-known physician who contributed greatly to the growth in knowledge over the past century of family patterns of cancer development. If you have never heard of Aldred Scott Warthin, a University of Michigan pathologist who worked in the early part of the 20th century, you are in plenteous company, but are probably not an ear, nose, and throat surgeon. Warthin managed to get his name attached to an uncommon tumor of the major salivary gland. That is his chief claim to fame today. He deserves more recognition for the largely unsung role he played in the early history of colorectal cancer genetics.

The great majority of cancers occur sporadically, meaning that they occur with seeming randomness within the general population. That oversimplifies matters, but it serves to distinguish a much smaller number of cancer cases that display a definite pattern of higher and more predictable occurrence within certain families. Roughly ten percent of all colorectal cancers cluster within families, and we can link an even smaller percentage of these cases to a proven inherited genetic change or mutation. Of these, the most common goes by the mouth-filling rubric of hereditary nonpolyposis colorectal cancer, mercifully abbreviated to HNPCC or often just called the Lynch syndrome, named after Dr. Henry T. Lynch, the widely-acknowledged father of modern cancer genetics who updated and refined the available information about certain families with cancer clusters and identified a specific pattern of inheritance. But perhaps, giving due credit that Dr. Lynch himself gave in 1985, we should think about calling this condition the Warthin-Lynch syndrome.

Travel back with me to 1895 in Ann Arbor, where young Dr. Warthin plied his skills in the University of Michigan pathology laboratories, investigating the various causes of diseases that afflicted the good people of southeastern Michigan. In those days, clothing came less frequently off the rack in large chain department stores and more often from local tailors and seamstresses. Dr. Warthin employed one such woman to keep his clothes in good repair. That year, she confided to him her concerns—and those of her family as a whole—that cancer seemed to occur with uncomfortable and mysterious frequency among her relatives. No one could fault her for worrying; indeed, she was right to do so, for eventually she succumbed to endometrial cancer. Intrigued, Dr. Warthin performed an oft-underutilized clinical investigation by completing an extensive family history. Questions about disease within your extended family may seem nosy and the information can be difficult to obtain in detail, but often it conveys invaluable insight otherwise elusive. The seamstress came from a family large by our standards, which likely helped bring the problem to light, for half the ten siblings came down with cancer. Two sisters had uterine cancer, two siblings had gastric cancer, and one suffered from an ill-defined “abdominal” cancer. Furthermore, descendants of these five persons themselves had multiple cancers, whereas none of the progeny of the five unaffected siblings developed the disease.

Dr. Warthin went back to his offices armed with this information. Many years later, having accumulated much more experience, he set out to examine records at the university hospital. He found about 1600 cases of malignant tumors in the span of years from 1895 to 1912. About 15% of these cases exhibited a familial pattern. In 1925, he updated his original findings from the family of the seamstress, documenting a remarkable increased incidence of cancers of the gastrointestinal tract and the uterus, as well as a younger-than-average age of onset for affected individuals. There were three particularly impressive cases in younger persons who presented for appendicitis care and were found instead to have advanced cancer involving the lower right colon.

Asthma suddenly claimed Dr. Warthin’s life in 1931. Colleagues published an update on the family of the seamstress (then known as “family G” because of their German heritage) with longer follow up of the various individuals within it, confirming the strong pattern of gastrointestinal cancers. After a period of no further progress, Dr. Lynch picked up the threads of this investigation in the mid 1960s, even going so far as to arrange a “family G” reunion near Ann Arbor and accomplishing an extensively detailed genetic investigation on his guests. Of the more than 650 family members, 95 had developed cancer, chiefly of the colon and uterus. Dr. Lynch discerned the dominant pattern of inheritance that characterizes this particular cancer syndrome. Further updates published in 2005 included specific information on one of the genetic mutations subsequently linked to the increased risk of cancer in affected persons, confirming in retrospect that this had been, all along, a disorder of genetics. It is now possible—and commonly done—to have blood testing to identify at-risk family members, who may then undergo more intensive screening or even have certain preventative procedures done.

I wrote in an earlier piece about the risk factors that should prompt screening for colorectal cancer. Certainly, informing your health care provider of a suspicious family history imparts an important impetus to appropriate risk reduction intervention. As is always the case with cancer, early recognition and treatment produces the most favorable outcomes. One might almost say that a stitch in time saves nine.
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