Olson S H, Finstad C L, Harlap S, Kurian L, Saigo P E, Barakat R R
Department of Epidemiology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer Epidemiol Biomarkers Prev. 1997 Oct;6(10):815-7.
We studied 54 patients diagnosed with endometrial cancer between 1981 and 1994 following a diagnosis of breast cancer. We used a case-case analysis, comparing tumors with and without overexpression of the p53 gene product to evaluate the association of putative p53 mutations with tamoxifen use and other risk factors for endometrial cancer. Twenty-four % of the tumors showed strong positive staining for the p53 gene product. Tumors in a more advanced stage (stage 2, 3, or 4, compared to stage 1) were more likely to overexpress p53 [odds ratio (OR) = 4.2; 95% confidence interval (CI), 1.1-16.2], as were tumors with serous or clear cell, compared to endometrioid, histology (OR = 5.8; 95% CI, 1.3-26.5). There was a small association between p53 overexpression and treatment with tamoxifen for breast cancer (OR = 2.6; 95% CI, 0.69-9.8). There was a strong relationship between overexpression of p53 and having a first-degree relative with breast cancer (OR = 12.3; 95% CI, 2.6-57.4) and between overexpression of p53 and having an additional cancer, i.e., at sites other than breast or endometrium (OR = 7.9; 95% CI, 1.6-40.1). In this group of women, genetic predisposition to cancer, as reflected in family history of breast cancer and personal history of an additional primary cancer, was strongly associated with overexpression of p53 in endometrial tumors. The results suggest that use of tamoxifen may be associated with an increase in tumors that overexpress p53, although the results could be due to chance.
我们研究了1981年至1994年间被诊断患有子宫内膜癌且此前已被诊断患有乳腺癌的54名患者。我们采用病例对照分析，比较p53基因产物过表达和未过表达的肿瘤，以评估假定的p53突变与他莫昔芬使用及子宫内膜癌其他危险因素之间的关联。24%的肿瘤对p53基因产物呈强阳性染色。与I期相比，处于更晚期（II、III或IV期）的肿瘤更可能过表达p53 [比值比（OR）= 4.2；95%置信区间（CI），1.1 - 16.2]，与子宫内膜样组织学相比，浆液性或透明细胞组织学的肿瘤也是如此（OR = 5.8；95% CI，1.3 - 26.5）。p53过表达与乳腺癌他莫昔芬治疗之间存在较小的关联（OR = 2.6；95% CI，0.69 - 9.8）。p53过表达与有乳腺癌一级亲属之间存在强关联（OR = 12.3；95% CI，2.6 - 57.4），且p53过表达与有其他癌症（即除乳腺或子宫内膜以外的部位）之间也存在强关联（OR = 7.9；95% CI，1.6 - 40.1）。在这组女性中，如乳腺癌家族史和其他原发性癌症个人史所反映的癌症遗传易感性与子宫内膜肿瘤中p53过表达密切相关。结果表明，使用他莫昔芬可能与过表达p53的肿瘤增加有关，尽管结果可能是偶然的。
