Circulating beta-2 microglobulin and risk of cancer: The atherosclerosis risk in communities study (ARIC)

Anna E. Prizment, Amy M. Linabery, Pamela L. Lutsey, Elizabeth Selvin, Heather H. Nelson, Aaron R. Folsom, Timothy R. Church, Charles G. Drake, Elizabeth A. Platz, Corinne Joshu

Research output: Contribution to journalArticle

Abstract

Background: Serum β-2 microglobulin (B2M), a major histocompatibility complex class I molecule that is a biomarker of kidney filtration and increased cell turnover, is elevated at the time of diagnosis in hematological and some solid cancers. However, serum B2M was not examined prospectively as a marker for cancer risk. We hypothesized that in a population without a prior cancer diagnosis, serumB2Mis associated with risk of cancer (n=2,436), including colorectal (n = 255), lung (n = 298), breast (n = 424), and prostate (n = 524) cancers, and hematological (n = 176) malignancies. Methods: The analytical cohort (n = 12,300) was followed for incident cancers from 1990 through 2006. B2M (range, 0.9-57.8 mg/L) was measured in stored serum collected in 1990-1992. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for cancer incidence and mortality in relation to quartiles of B2M. Results: Adjusting for age, sex, race, center, education, body mass index, smoking, aspirin, and hormone therapy (in women) and comparing highest to lowest B2M quartiles, HRs were 1.25 (1.06-1.47; Ptrend = 0.002) for total cancer risk and 2.21 (1.32-3.70; Ptrend=0.001) for colorectal cancer risk, with similar HRs for colon and rectal cancers. These associations remained after adjustment for an inflammatory biomarker, C-reactive protein, and after excluding the first three years of follow-up. Significant associations were also observed for mortality from total, lung, and hematological cancers. Conclusions: These findings provide the first evidence that higher serum B2M is associated with increased colorectal cancer risk. Impact: This study supports B2M as a potential biomarker for colorectal cancer risk.

Original languageEnglish (US)
Pages (from-to)657-664
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume25
Issue number4
DOIs
StatePublished - Apr 2016

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ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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