Affiliations of authors: Womens College Research Institute, Womens College Hospital (MRA, SAN), Dalla Lana School of Public Health (MRA, JM, SAN), Samuel Lunenfeld Research Institute (JM), University of Toronto, Toronto, Canada; Genome Quebec Innovation Centre, McGill University, Montreal, Canada (PL); Department of Gynecology-Oncology (BR), and Department of Medical Oncology (MM), Princess Margaret Hospital, Toronto, Canada; Department of Epidemiology and Public Health, School of Public Health, School of Medicine, Yale University, New Haven, CT (HR).
J Natl Cancer Inst. 2014 Jan;106(1):djt323. doi: 10.1093/jnci/djt323. Epub 2013 Nov 21.
We compared the frequency of PPM1D mutation in the white blood cells from 1295 ovarian cancer case patients and 834 control subjects. We found a truncating mutation in 20 case patients vs 1 control subject (odds ratio [OR] = 13.07; 95% confidence interval [CI] = 1.75 to 97.55; P < .001). The 12-year mortality of the PPM1D-positive case patients was higher than that of the PPM1D-negative case patients (hazard ratio = 2.02; 95% CI = 1.21 to 3.39; P = .007). Three of the 20 PPM1D carrier case patients had a past history of breast cancer compared with 29 of 1129 noncarriers (OR = 6.69; 95% CI = 1.86 to 24.11; P = .007). The lifetime risks for breast or ovarian cancer among female first-degree relatives of PPM1D mutation carriers were not increased compared with that of case patients without mutations. These observations suggest PPM1D mutations in the mosaic state predispose women to breast and ovarian cancer in the absence of a family history of cancer.
我们比较了 1295 例卵巢癌病例患者和 834 例对照者白细胞中 PPM1D 突变的频率。我们在 20 例病例患者中发现了一个截断突变，而在 1 例对照者中未发现（比值比[OR] = 13.07；95%置信区间[CI] = 1.75 至 97.55；P <.001）。PPM1D 阳性病例患者的 12 年死亡率高于 PPM1D 阴性病例患者（风险比= 2.02；95%CI = 1.21 至 3.39；P =.007）。20 名 PPM1D 携带者病例患者中有 3 人有乳腺癌病史，而在 1129 名非携带者中仅有 29 人（OR = 6.69；95%CI = 1.86 至 24.11；P =.007）。与无突变的病例患者相比，PPM1D 突变携带者的女性一级亲属患乳腺癌或卵巢癌的终生风险并未增加。这些观察结果表明，镶嵌状态下的 PPM1D 突变使女性在没有癌症家族史的情况下易患乳腺癌和卵巢癌。
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