Ruth Kleinerman Studies Radiation and Second Cancers

"Finding the first clear evidence of the gene-environment interactions underlying the excess risk of secondary cancers in patients with retinoblastoma has been a most gratifying accomplishment," says Ruth A. Kleinerman, M.P.H., an epidemiologist with the Radiation Epidemiology Branch (REB). She has reason to celebrate: this year marks her 30th anniversary with NCI and 30 years of extraordinary productivity in cancer research. Using the collaborative approach that is the linchpin of successful epidemiologic studies, she has established risk factors for several forms of cancer.

Ms. Kleinerman's work has been featured in more than 100 articles published in peer-reviewed journals. Not only has she been the recipient of both group and individual NIH Merit awards, but she also has twice received the DCEG Award for Outstanding Research Paper by a Staff Scientist. Perhaps her greatest achievement, however, has been her major discoveries in ophthalmic oncology.

Retinoblastoma, a cancer that develops in the tissues of the retina, usually occurs in children younger than five years of age and can be either hereditary or nonhereditary (i.e., sporadic). Children with retinoblastoma have excellent survival rates, up to 97 percent at five years. However, children who survive hereditary retinoblastoma have substantially increased risks of developing second primary cancers.

Ms. Kleinerman established a cohort of retinoblastoma survivors during the mid-1980s and has been following them for decades. She has found that those with the hereditary form of retinoblastoma are also at elevated risk for bone and soft tissue sarcomas, melanoma, and brain tumors due to a germline mutation in their RB-1 gene, which encodes the cell cycle regulatory protein pRb. She observed the excess risk of secondary cancers to be primarily among children with hereditary retinoblastoma who receive radiotherapy and to persist in a dose-dependent manner throughout the adult years.

"Finding a dose-related relationship between radiation exposure and second cancers has transformed the care given to children with hereditary retinoblastoma," she explains. "The goal of treatment today is to minimize radiotherapy exposure in these patients and intensify cancer-screening efforts throughout their lives."

According to Dr. David Abramson, Chief of the Ophthalmic Oncology Service at Memorial Sloan-Kettering Cancer Center and a longtime collaborator, "Ms. Kleinerman's papers have dramatically changed our understanding of retinoblastoma and the way in which the disease is managed worldwide."

Not only does Ms. Kleinerman continue to follow the original retinoblastoma cohort, but she also has established cohorts of patients who have been treated more recently, and she is following them using innovative methods. "We are using new internet tools such as Facebook to reach out to retinoblastoma survivors who are now in their twenties. In addition, we will soon launch a Web site to seek out retinoblastoma survivors and provide screening information," Ms. Kleinerman reports. "It will be interesting to see how well social media works for contacting potential members of this cohort."

Within DCEG, Ms. Kleinerman is known for her successful collaborations, both here and abroad. She became involved in a study of families with ataxia-telangiectasia (a rare, childhood neurological disorder that causes degeneration in the part of the brain controlling motor movements and speech) using Nordic cancer registries. In 2005, she organized a joint meeting of several European groups to pursue observations of increased cancer incidence in affected families.

Among the many other interesting studies with which she has been involved was one in Gansu Province, China, where more than half the population lives underground in so-called "cave dwellings" with significantly elevated radon levels. The research team found a direct link between the risk of lung cancer and the levels of exposure measured through radon detectors. Ms. Kleinerman recounts, "I was very fortunate to have the opportunity to travel to a rural part of China and carry out research that uncovered a very clear health risk to residents living within the area."

Still in the beginning stages is a study of cancer mortality among interventional radiologists and cardiologists. As the numbers of fluoroscopically guided procedures and higher-dose diagnostic x-ray examinations have increased over recent decades, so too have concerns about radiation exposure to patients and physicians. In collaboration with other REB investigators, Ms. Kleinerman is now assembling a cohort of specialty groups and exploring different ways of assessing their radiation exposure and subsequent risks of cancer.

Ms. Kleinerman earned her master's degree in public health at the Boston University School of Public Health and holds an undergraduate degree in art history from Washington University in St. Louis. She counts herself lucky to live in Washington, DC, where she has plenty of opportunities to indulge her love of fine art at the city’s myriad art museums and galleries.

—Karen Eddleman

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