Furberg H, Millikan R C, Geradts J, Gammon M D, Dressler L G, Ambrosone C B, Newman B
Derald H. Ruttenberg Cancer Center, Mt. Sinai School of Medicine, New York, NY 10029-6574, USA.
Cancer Causes Control. 2003 Sep;14(7):609-18. doi: 10.1023/a:1025682410937.
To evaluate the potential etiologic heterogeneity of breast cancer by examining whether associations with reproductive and other personal characteristics differed by p53 protein expression status.
Data from the Carolina Breast Cancer Study, a population-based, case-control study of 861 cases and 790 controls, were utilized. Immunohistochemical staining for the p53 protein was performed on 638 archived tumor specimens; 46% of cases were classified as p53+. Two separate unconditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for p53+ and p53- breast cancer relative to controls for reproductive and other personal characteristics. Analyses were performed separately for younger (< or = 45 years) and older (>45 years) women.
Risk factor profiles largely overlapped for p53+ and p53- breast cancer, with the exception of oral contraceptive (OC) use among younger women and a family history of breast cancer. Prolonged OC use was more strongly associated with p53+ breast cancer [OR 3.1 (95% CI: 1.2-8.1) than p53- breast cancer (OR 1.3 (95% CI: 0.6-3.2)] among younger women only. A first-degree family history of breast cancer was associated with p53+ breast cancer among younger women [OR 1.5 (95% CI: 1.0-2.2)] and older women [OR 1.4 (95% CI: 0.9-2.3)], but not p53- breast cancer in either age-group.
These results provide little evidence of breast cancer heterogeneity as classified by p53 expression status. However, although not statistically significant, OC use among younger women and family history of breast cancer may operate through a pathway involving p53 alterations to increase risk of breast cancer.
通过研究与生殖及其他个人特征的关联是否因p53蛋白表达状态不同而有所差异,评估乳腺癌潜在的病因异质性。
利用卡罗来纳乳腺癌研究的数据,这是一项基于人群的病例对照研究,包括861例病例和790例对照。对638份存档肿瘤标本进行p53蛋白的免疫组化染色;46%的病例被分类为p53阳性。使用两个独立的非条件逻辑回归模型来计算p53阳性和p53阴性乳腺癌相对于对照在生殖及其他个人特征方面的优势比(OR)和95%置信区间(CI)。分别对年轻(≤45岁)和年长(>45岁)女性进行分析。
p53阳性和p53阴性乳腺癌的危险因素概况基本重叠,但年轻女性使用口服避孕药(OC)情况和乳腺癌家族史除外。仅在年轻女性中,长期使用OC与p53阳性乳腺癌的关联更强[OR 3.1(95%CI:1.2 - 8.1)],而与p53阴性乳腺癌的关联较弱[OR 1.3(95%CI:0.6 - 3.2)]。一级乳腺癌家族史在年轻女性[p53阳性乳腺癌的OR 1.5(95%CI:1.0 - 2.2)]和年长女性[p53阳性乳腺癌的OR 1.4(95%CI:0.9 - 2.3)]中与p53阳性乳腺癌相关,但在两个年龄组中均与p53阴性乳腺癌无关。
这些结果几乎没有提供按p53表达状态分类的乳腺癌异质性的证据。然而,尽管无统计学意义,但年轻女性使用OC情况和乳腺癌家族史可能通过涉及p53改变的途径增加乳腺癌风险。