Intraindividual Variability in Arsenic Methylation in a U.S. Population

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 14; no. 4; pp. 919 - 924
• Main Authors: STEINMAUS, Craig, YAN YUAN, KALMAN, Dave, ATALLAH, Raja, SMITH, Allan H
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-04-2005
• Subjects: Aged; Arsenic; Arsenic - adverse effects; Arsenic - metabolism; Arsenic - urine; Biological and medical sciences; Case-Control Studies; Environmental carcinogenesis/toxicology; Epidemiology; Female; Humans; Male; Medical sciences; Methylation; Middle Aged; Registries; Spectrophotometry, Atomic; Tumors; United States; Urinary Bladder Neoplasms - chemically induced; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - urine; United States; North America; America; Human; Carcinogen; Cancerology; Arsenic; Intraindividual comparison; Risk factor; Malignant tumor; Methylation; Epidemiology; Public health
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-04-0277

Several recent investigations have reported associations between a reduced capacity to fully methylate inorganic arsenic and
increased susceptibility to arsenic-caused cancer. In these studies, methylation patterns were based on a single assessment
of urinary arsenic metabolites collected at the time of cancer diagnosis. However, the latency of arsenic-caused cancer may
be several decades, and the extent to which a recent measurement can be used to estimate a person's past methylation pattern
is unknown. In this investigation, the distribution of urinary inorganic arsenic, monomethylarsonate, and dimethylarsinate
was used to assess intraindividual variation in methylation capacity in 81 subjects with low to moderate arsenic exposures.
Multiple urine samples were collected from each subject over a 1-year period. Duplicate analyses done on 27 samples were used
to assess laboratory measurement imprecision. The intraclass correlation coefficients (ICC) for the proportion of urinary
arsenic as inorganic arsenic, monomethylarsonate, and dimethylarsinate in samples taken an average of 258 days apart, were
0.45 [95% confidence interval (95% CI), 0.23-0.63] 0.46 (95% CI, 0.24-0.64), and 0.49 (95% CI, 0.28-0.66). In analyses of
duplicate samples, ICCs for the concentration of arsenic species ranged from 0.87 to 0.93, whereas ICCs for species proportions
ranged from 0.63 to 0.76. These data suggest that individual methylation patterns remain fairly stable over time, although
variability due to measurement imprecision or intraindividual changes over time does occur. This variability could lead to
misclassification of methylation patterns and could bias relative risk estimates in studies of methylation and cancer towards
the null.