Fetal microchimerism in breast and colon cancer
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1574 Background: Cells acquired by a woman from her baby that durably persist in her blood and tissues is known as fetal microchimerism (FMc). In women with breast cancer, frequency and quantity of FMc in blood and breast tissue is reduced compared to healthy women. Whether the absence of fetal microchimerism predicts risk for developing breast cancer is unknown. FMc was evaluated in buffy coat cells from presumed healthy women who later developed breast cancer or colon cancer, a cancer in which prior pregnancy appears protective but has different associations with endocrine risk factors.
METHODS: Women studied were participants in the Danish Diet, Cancer and Health study. They were recruited from December 1993 to May 1997, aged 50-65 at the time of recruitment (interview, demographic and risk-factor questionnaire, and phlebotomy), and prospectively monitored for health outcomes including cancer. DNA from repository buffy coat specimens was tested for male FMc with quantitative PCR targeting the DYS14gene on the Y chromosome. For this analysis, 89 women who developed breast cancer and 67 women who developed colon cancer were evaluable for FMc. Results were compared to 272 women who remained cancer free.
RESULTS: Compared to cancer-free women, FMc was detected less frequently in breast cancer patients (40.5% vs. 69.9%, age-adjusted OR==0.38, 95%CI of 0.25-0.58). The inverse association of FMc with breast cancer was consistent across cancer specific factors (receptor status, primary size, nodal involvement, TNM stage, and histology). Compared to cancer-free women, FMc was positively associated with developing colon cancer (89.6%, age-adjusted OR==3.05, 95%CI of 1.39-6.69). There was both a trend of increasing frequency of FMc temporally closer to diagnosis, <4 years versus > 8years since phlebotomy (p==0.02) and of increasing concentrations of FMc (p<0.01) with developing colon cancer, but neither trend was detected for breast cancer (p==0.75 and 0.34, respectively).
CONCLUSIONS: Women who fail to acquire or maintain detectable FMc in the blood are at higher risk of developing breast cancer. Surprisingly, women who develop colon cancer harbored FMc more frequently than cancer-free women. FMc is a risk factor unexplored in many cancers. Mechanistic studies are warranted.
|Journal||Journal of Clinical Oncology|
|Publication status||Published - 20 May 2011|