Yasui Y, Potter J D, Stanford J L, Rossing M A, Winget M D, Bronner M, Daling J
Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.
Cancer Epidemiol Biomarkers Prev. 2001 Jan;10(1):9-16.
Parallel to its established causal association with both infectious mononucleosis (IM) and young adulthood Hodgkin disease (YAHD), we propose a hypothesis that "delayed" primary EBV infection (i.e., primary infection occurring during adolescence or adulthood) is associated with elevated breast cancer risk. We evaluated this hypothesis with two investigations, one descriptive and the other analytic. The descriptive study used international/United States cancer registry data to assess the association between incidence rates of breast cancer and those of YAHD. The incidence rates of the seemingly unrelated neoplasms were strongly correlated (correlation coefficients of 0.74 and 0.88 for international and United States data, respectively; these were higher than the correlation coefficients of YAHD with two other cancers that we considered). Populations with higher incidence rates corresponded to those with higher likelihood of delayed primary EBV infection. The analytical study was based on a population-based case-control study of breast cancer in middle-aged women. Age-adjusted odds ratios of breast cancer in women who reported a history of IM, relative to women who did not, increased monotonically from 0.55 [95% confidence interval (CI), 0.05-6.17] for women with 0-9 years of age at IM onset to 2.67 (CI, 1.04-6.89) for women with > or =25 years of age at IM onset (P = 0.016). An older age at tonsillectomy, another surrogate of delayed EBV exposure, was also associated with increased risk of breast cancer: odds ratios, 0.92 (CI, 0.57-1.48) and 1.76 (CI, 1.15-2.69) for women with tonsillectomy at 0-4 years of age and > or =15 years of age, respectively (P = 0.018). Adjusting for additional potential confounders did not modify the associations appreciably. The implications of the findings and a potential biological mechanism are presented.
鉴于EB病毒（EBV）与传染性单核细胞增多症（IM）和青年期霍奇金病（YAHD）之间已确立的因果关联，我们提出一个假说：“延迟”的原发性EBV感染（即在青春期或成年期发生的原发性感染）与乳腺癌风险升高相关。我们通过两项研究对这一假说进行了评估，一项是描述性研究，另一项是分析性研究。描述性研究利用国际/美国癌症登记数据来评估乳腺癌发病率与YAHD发病率之间的关联。这两种看似不相关肿瘤的发病率呈强相关（国际数据和美国数据的相关系数分别为0.74和0.88；这些系数高于我们所考虑的YAHD与其他两种癌症的相关系数）。发病率较高的人群与原发性EBV感染延迟可能性较高的人群相对应。分析性研究基于一项针对中年女性乳腺癌的人群病例对照研究。报告有IM病史的女性相对于无IM病史的女性，经年龄调整后的乳腺癌优势比从IM发病时年龄为0 - 9岁的女性的0.55[95%置信区间（CI），0.05 - 6.17]单调增加至IM发病时年龄≥25岁的女性的2.67（CI，1.04 - 6.89）（P = 0.016）。扁桃体切除术年龄较大，这是EBV暴露延迟的另一个替代指标，也与乳腺癌风险增加相关：扁桃体切除术年龄在0 - 4岁和≥15岁的女性的优势比分别为0.92（CI，0.57 - 1.48）和1.76（CI，1.15 - 2.69）（P = 0.018）。对其他潜在混杂因素进行调整后，这些关联没有明显改变。本文还阐述了研究结果的意义及潜在的生物学机制。
