Many human cancers are caused by environmental and lifestyle factors. Biomarkers of exposure and risk developed by our team have provided critical data on internal exposure to toxic and genotoxic chemicals and their connection to cancer in humans. This review highlights our research using biomarkers to identify key factors influencing cancer risk as well as their application to assess the effectiveness of exposure intervention and chemoprevention protocols. The use of these biomarkers to understand individual susceptibility to the harmful effects of tobacco products is a powerful example of the value of this type of research and has provided key data confirming the link between tobacco smoke exposure and cancer risk. Furthermore, this information has led to policy changes that have reduced tobacco use and consequently, the tobacco-related cancer burden. Recent technological advances in mass spectrometry led to the ability to detect DNA damage in human tissues as well as the development of adductomic approaches. These new methods allowed for the detection of DNA adducts in tissues from patients with cancer, providing key evidence that exposure to carcinogens leads to DNA damage in the target tissue. These advances will provide valuable insights into the etiologic causes of cancer that are not tobacco-related.
Bibliographical noteFunding Information:
This work was supported by the NCI grants P01 CA138338 (to S.S. Hecht, S.E. Murphy, N.Y. Tretyakova, I. Stepanov, L.A. Peterson, D.K. Hatsukami), R01 CA81301 (to S.S. Hecht), R01 CA222005 (to S.S. Hecht), U19 CA157345 (to D.K. Hatsukami, S.S. Hecht, S.E. Murphy, I. Stepanov), U54 DA031659 (to D.K. Hatsukami, S.S. Hecht, S.E. Murphy, I. Stepanov), R01 CA122320 (to R.J. Turesky), R01 CA220367 (to R.J. Turesky), R01 ES019564 (to R.J. Turesky), R33 CA186795 (to R.J. Turesky), R50 CA211256 (to P.W. Villalta), R01 CA179246 (to I. Stepanov), U01 DA045523 (to I. Stepanov), and R01 CA220376 (to S. Balbo). The authors are also part of the Human Health Exposure Assessment Resource (HHEAR) supported by the National Institute of Environmental Health Sciences grant U2CES026533. The Masonic Cancer Center Analytical Biochemistry Shared Resource is funded in part by NCI grant P30 CA77598. I. Stepanov is supported in part by startup funding from Minnesota Masonic Charities. The authors thank Mr. Bob Carlson for his assistance with the figures and other editorial matters. The authors also thank their many collaborators, including Dr. Loic Le Marchand at the University of Hawaii (Honolulu, HI); Ms. Yesha Patel, Dr. Christopher Haiman, Dr. Daniel Stram, and Dr. Sungshim Park at the University of Southern California (Los Angeles, CA); Dr. Jian-Min Juan at the University of Pittsburgh (Pittsburgh, PA); Dr. James Swenberg at the University of North Carolina (Chapel Hill, NC); Dr. Vernon Walker at the University of Vermont; Dr. Ivan Rusyn at Texas A&M University (College Station, TX); Dr. Thomas A. Rosenquist, Dr. Kathleen G. Dickman, and Dr. Arthur P. Grollman at Stony Brook University (Stony Brook, NY); and Dr. Byeong Hwa Yun, Dr. Medjda Bellamri, Dr. Jingshu Guo, Dr. Paari Murugan, and Dr. Christopher J. Weight at the University of Minnesota (Minneapolis, MN).
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