Prizment Anna E, Linabery Amy M, Lutsey Pamela L, Selvin Elizabeth, Nelson Heather H, Folsom Aaron R, Church Timothy R, Drake Charles G, Platz Elizabeth A, Joshu Corinne
Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota. University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota.
University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota. Division of Epidemiology and Clinical Research, University of Minnesota Department of Pediatrics, Minneapolis, Minnesota.
Cancer Epidemiol Biomarkers Prev. 2016 Apr;25(4):657-64. doi: 10.1158/1055-9965.EPI-15-0849. Epub 2016 Feb 5.
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, serum B2M is 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.
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.
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.
These findings provide the first evidence that higher serum B2M is associated with increased colorectal cancer risk.
This study supports B2M as a potential biomarker for colorectal cancer risk. Cancer Epidemiol Biomarkers Prev; 25(4); 657-64. ©2016 AACR.
血清β-2微球蛋白（B2M）是一种主要组织相容性复合体I类分子，是肾脏滤过和细胞更新增加的生物标志物，在血液系统癌症和一些实体癌诊断时会升高。然而，血清B2M尚未作为癌症风险标志物进行前瞻性研究。我们假设，在未患过癌症的人群中，血清B2M与癌症风险（n = 2436）相关，包括结直肠癌（n = 255）、肺癌（n = 298）、乳腺癌（n = 424）、前列腺癌（n = 524）以及血液系统恶性肿瘤（n = 176）。
对分析队列（n = 12300）进行随访，观察1990年至2006年期间的新发癌症情况。在1990 - 1992年收集的储存血清中检测B2M（范围为0.9 - 57.8 mg/L）。采用Cox比例风险模型估计与B2M四分位数相关的癌症发病率和死亡率的风险比（HR）及95%置信区间。
在调整年龄、性别、种族、中心、教育程度、体重指数、吸烟、阿司匹林使用情况以及女性的激素治疗情况后，将B2M最高四分位数与最低四分位数进行比较，总癌症风险的HR为1.25（1.06 - 1.47；Ptrend = 0.002），结直肠癌风险的HR为2.21（1.32 - 3.70；Ptrend = 0.001），结肠癌和直肠癌的HR相似。在调整炎症生物标志物C反应蛋白后以及排除随访的前三年后，这些关联依然存在。在总癌症、肺癌和血液系统癌症的死亡率方面也观察到显著关联。
这些发现首次证明血清B2M水平升高与结直肠癌风险增加相关。
本研究支持B2M作为结直肠癌风险的潜在生物标志物。《癌症流行病学、生物标志物与预防》；25(4)；657 - 64。©2016美国癌症研究协会。
