Appalachian Kentucky (App KY) leads the nation in lung cancer incidence and mortality. Trace elements, such as As, have been associated with lung cancers in other regions of the country and we hypothesized that a population-based study would reveal higher trace element concentrations in App KY individuals with cancer compared to controls. Using toenail and drinking water trace element concentrations, this study investigated a possible association between lung cancer incidence and trace-element exposure in residents of this region. This population-based case-control study had 520 subjects, and 367 subjects provided toenail samples. Additionally, we explored the relationship between toenail and fingernail trace-element concentrations to determine if fingernails could be used as a surrogate for toenails when patients are unable to provide toenail samples. We found that, contrary to our initial hypothesis, trace element concentrations (Al, As, Cr, Mn, Co, Fe, Ni, Cu, Se, and Pb) were not higher in cancer cases than controls with the exception of Zn where concentrations were slightly higher in cases. In fact, univariate logistic regression models showed that individuals with lower concentrations of several elements (Al, Mn, Cr, and Se) were more likely to have lung cancer, although only Mn was significant in multivariate models which controlled for confounding factors. While drinking water concentrations of Al, Cr and Co were positively related to cancer incidence in univariate models, only Co remained significant in multivariate models. However, since the drinking water concentrations were extremely low and not reflected in the toenail concentrations, the significance of this finding is unclear. We also found that fingernail concentrations were not consistently predictive of toenail concentrations, indicating that fingernails should not be used as surrogates for toenails in future studies.
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This research was supported by the U.S. Army Medical Research and Materiel Command through grant number W81XWH-11-1-0781. Supplemental support was provided by the Analytical Core of the Center for Appalachian Research in Environmental Sciences, National Institute of Environmental Health Sciences grant number 1P30ES026529-01A1. This research was supported by the Biostatistics and Bioinformatics, Cancer Research Informatics, and Biospecimen and Tissue Procurement Shared Resources of the University of Kentucky Markey Cancer Center which is funded by the National Cancer Institute through P30CA177558.
Data cannot be shared publicly to protect the privacy of the human subjects. Data are available from the Markey Cancer Center Data Repository (https://mcclabkey.uky.edu/labkey/project/home/begin.view?) for researchers who meet the criteria for access to human subjects data. To access the data, please contact the database administrator, Bront Davis at (firstname.lastname@example.org) and request access to data from the LCRI DoD Lung Cancer Study.
S1 Table. Full cohort demographics broken down by case versus control. https://doi.org/10.1371/journal.pone.0212340.s001 (PDF)
S2 Table. Full cohort demographics broken down by those who provided toenails (nails) versus those who didn’t (no-nails). https://doi.org/10.1371/journal.pone.0212340.s002 (PDF)
S3 Table. https://doi.org/10.1371/journal.pone.0212340.s003 (PDF)
S4 Table. Recovery of trace elements from National Institute of Environmental Sciences (Japan) certified reference material number 13 (Human Hair). https://doi.org/10.1371/journal.pone.0212340.s004 (PDF)
S5 Table. Quintiles of trace-element concentrations in toenails (μg/g dry mass) broken down by case versus control, age and smoking status. https://doi.org/10.1371/journal.pone.0212340.s005 (PDF)
S6 Table. Quintiles of drinking water trace element concentrations and method detection limits. https://doi.org/10.1371/journal.pone.0212340.s006 (PDF)
Unrine, Jason M.; Slone, Stacey A.; Sanderson, Wayne T.; Johnson, Nancy E.; Durbin, Eric B.; Shrestha, Shristi; Hahn, Ellen J.; Feltner, Fran; Huang, Bin; Christian, W. Jay; Mellon, Isabel; Orren, David K.; and Arnold, Susanne M., "A Case-Control Study of Trace-Element Status and Lung Cancer in Appalachian Kentucky" (2019). Plant and Soil Sciences Faculty Publications. 142.
S1 Table. Full cohort demographics broken down by case versus control.
journal.pone.0212340.s002.pdf (202 kB)
S2 Table. Full cohort demographics broken down by those who provided toenails (nails) versus those who didn’t (no-nails).
journal.pone.0212340.s003.pdf (227 kB)
journal.pone.0212340.s004.pdf (92 kB)
S4 Table. Recovery of trace elements from National Institute of Environmental Sciences (Japan) certified reference material number 13 (Human Hair).
journal.pone.0212340.s005.pdf (240 kB)
S5 Table. Quintiles of trace-element concentrations in toenails (μg/g dry mass) broken down by case versus control, age and smoking status.
journal.pone.0212340.s006.pdf (163 kB)
S6 Table. Quintiles of drinking water trace element concentrations and method detection limits.