University of Copenhagen, Institute of Public Health, Section of Social Medicine, Øster Farimagsgade 5, Post Box 2099, DK-1014 Copenhagen K, Denmark.
Eur J Cancer. 2012 Sep;48(14):2227-35. doi: 10.1016/j.ejca.2012.02.006. Epub 2012 Mar 5.
Detection of Y chromosome, thought to originate from previous pregnancies with a male fetus, is common in women. Lower concentrations have been reported in women with breast cancer than cancer-free women. Data in women with other types of cancer are sparse. The purpose of the study was to determine whether the lower concentrations predate cancer diagnosis, and whether a possible beneficial effect was specific to breast cancer.
We conducted a prospective case-cohort study of 50-64-year-old Danish women enrolled in the diet, cancer and health cohort. Blood samples and questionnaire data were obtained during 1993-1997 when all women were cancer-free. In 2006 all women were followed up for incident breast and colon cancer in national registers. In blinded analyses, we analysed buffy coat DNA for Y chromosome (DYS14) as a marker of male microchimerism.
We detected male microchimerism in 70% of 272 cancer-free women, 40% of 89 women who later developed breast cancer, and 90% of 67 women who later developed colon cancer. The corresponding odds ratios were 0.30 (95% confidence interval (CI) 0.17-0.52) for breast, and 3.9 (95%CI 1.6-9.5) for colon cancer.
Detection of male microchimerism was strongly associated with reduced risk of developing breast cancer and also the increased risk of developing colon cancer. Confirmatory findings based on an improved study design, failure to identify important confounders and the strength of the associations lead us to believe that microchimerism may be highly relevant to later cancer development. However, the present study does not allow us to identify the underlying biological mechanisms.
在女性中，检测到来源于先前怀有男性胎儿的 Y 染色体是很常见的。据报道，患有乳腺癌的女性 Y 染色体浓度较低，而未患癌症的女性则较高。患有其他类型癌症的女性的数据较少。本研究的目的是确定较低的浓度是否先于癌症诊断，以及可能的有益影响是否仅限于乳腺癌。
我们进行了一项前瞻性病例对照研究，研究对象为参加饮食、癌症和健康队列的 50-64 岁丹麦女性。在所有女性均未患癌症的 1993-1997 年间，采集了血液样本和问卷调查数据。2006 年，所有女性均在国家登记处随访乳腺癌和结肠癌的发病情况。在盲法分析中，我们分析了白细胞 DNA 中的 Y 染色体（DYS14）作为男性微嵌合体的标志物。
我们在 272 名无癌症的女性中检测到 70%存在男性微嵌合体，89 名随后患乳腺癌的女性中有 40%存在，67 名随后患结肠癌的女性中有 90%存在。相应的比值比分别为乳腺癌 0.30（95%置信区间 0.17-0.52），结肠癌 3.9（95%置信区间 1.6-9.5）。
检测到男性微嵌合体与降低患乳腺癌的风险强烈相关，也与患结肠癌的风险增加相关。基于改进的研究设计、未发现重要混杂因素以及关联的强度得出的确认性发现，使我们相信微嵌合体可能与以后的癌症发展高度相关。然而，本研究尚不能确定潜在的生物学机制。
