Abstract 257: Circulating beta-2 microglobulin and risk of cancer: the Atherosclerosis Risk in Communities (ARIC) Study

Serum β-2-microglobulin (B2M), a novel biomarker of kidney function, is elevated at the time of diagnosis or thereafter in many cancers including solid and hematological cancers. B2M function may be related to its pro-inflammatory or growth promoting properties or, alternatively, B2M may serve as inflammatory marker. However, serum B2M has not been examined as a marker for future cancer risk. We hypothesized that in cancer-free people, serum B2M may be associated with increased risk of all cancers combined (n=2,436), the 4 most common solid cancers - colorectal (n=271), lung (n=330), prostate (n=550), breast (n=439) individually, and hematological (n=189) cancers combined. Our main hypothesis a priori was that, in a prospective ARIC study, B2M is positively associated with the risks of (a) colorectal cancer, given its consistent association with inflammation, and (b) hematological cancers, due to the established role of B2M in the progression of myeloma and lymphoma. The analytical cohort (n=12,300; 55% women, 26% blacks and 74% whites, aged 47-70 y in 1990-92) was followed for 17 y until 2006. Serum B2M (0.9-57.8 mg/L) was measured in samples from 1990-92. Incident cancers were identified by linkage to cancer registries and supplemented by hospital records. Cox proportional hazards models estimated hazard ratios (HR) and 95% CI for cancers in relation to B2M presented as quartiles. The models were adjusted for age, sex, race, study center, education, BMI, smoking, aspirin use, hormone therapy, and the index of kidney function - estimated glomerular filtration rate. The breast cancer analysis was further adjusted for age at menarche, number of live births, and menopausal status. Higher B2M was associated with older age, higher prevalence of whites, higher BMI, greater pack-years of smoking and aspirin use, and lower education level. In a fully adjusted model, B2M was associated with the risk of total (HR=1.22, 1.04-1.43; P-trend=0.004) and colorectal cancers (HR=1.90, 1.14-3.17; P-trend=0.01) for the highest versus lowest of B2M quartile, with similar HRs for colon and rectal cancers. Of note, the trend for hematological cancers was not significant (HR=1.67 for the highest versus lowest of B2M quartile, P-trend=0.09). B2M-cancer associations did not change after the adjustment for other inflammatory markers (CRP or WBC count) or after excluding those with B2M >3mg/L, i.e., people who could have existing renal disease. Likewise, the associations for colorectal and total cancer remained significant after excluding people with acute inflammatory response (CRP >10mg/L) or cancer cases with This study provides the first evidence that elevated serum B2M precedes diagnosis of colorectal cancers, most likely due to B2M role as an inflammatory marker. The robust positive association observed for colorectal cancer supports the role of low-grade systemic inflammation as a risk factor for colorectal cancer development. Citation Format: Anna E. Prizment, Amy N. Linabery, Pamela Lutsey, Heather H. Nelson, Aaron R. Folsom, Corinne Joshu, Elizabeth A. Platz, Elizabeth Selvin. Circulating beta-2 microglobulin and risk of cancer: the Atherosclerosis Risk in Communities (ARIC) Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 257. doi:10.1158/1538-7445.AM2014-257