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大块 DNA 加合物与前瞻性 EPIC-Italy 研究中的乳腺癌风险。

Bulky DNA adducts and breast cancer risk in the prospective EPIC-Italy study.

机构信息

Molecular and Nutritional Epidemiology Unit, ISPO (Cancer Research and Prevention Institute), Ponte Nuovo, Via delle Oblate 2, 50139, Florence, Italy.

出版信息

Breast Cancer Res Treat. 2011 Sep;129(2):477-84. doi: 10.1007/s10549-011-1472-8. Epub 2011 Mar 31.

Abstract

The role of environmental carcinogen exposure in breast cancer development has long been suspected, but no specific association has been identified so far. A few molecular epidemiology studies reported that DNA adducts detected by different methods are associated with a modest increase of breast cancer risk. We aimed to evaluate the association between bulky DNA adducts, detected by the (32)P-postlabelling method in peripheral leukocytes, and the risk of developing breast cancer in the female Italian cohorts of the EPIC (European Prospective Investigation into Cancer and nutrition) study. By using a nested case-control design, breast cancer cases identified in the follow-up of over 30,000 women of EPIC-Italy study have been matched to controls by specific criteria. We measured the levels of bulky DNA adducts by the (32)P-postlabelling method in peripheral leukocytes donated at enrolment. Conditional regression analyses adjusted for selected potential confounders were used. Results on DNA adduct levels were available for 292 cases and 292 matched controls. The mean DNA adduct levels were similar in both groups (P=0.62). Multivariate regression analyses failed to show any significant association between bulky DNA adducts and breast cancer. Our results do not support any association of breast cancer risk with exposure to environmental carcinogens as measured through the levels of bulky DNA adducts in pre-diagnostic white blood cells. Larger studies by using different methods and/or biomarkers are needed to better evaluate the role of specific environmental carcinogens in breast carcinogenesis.

摘要

环境致癌物暴露在乳腺癌发展中的作用早已受到怀疑,但迄今为止尚未确定任何具体的关联。一些分子流行病学研究报告称,通过不同方法检测到的 DNA 加合物与乳腺癌风险略有增加有关。我们旨在评估外周白细胞中(32)P-后标记法检测到的大体积 DNA 加合物与女性意大利人群中 EPIC(欧洲癌症前瞻性调查和营养)研究中乳腺癌发病风险之间的关联。通过使用巢式病例对照设计,在 EPIC-Italy 研究中对超过 30000 名女性进行随访时发现的乳腺癌病例与对照组按特定标准匹配。我们在入组时使用(32)P-后标记法测量外周白细胞中大体积 DNA 加合物的水平。使用调整了选定潜在混杂因素的条件回归分析进行分析。在 292 例病例和 292 例匹配对照中获得了关于 DNA 加合物水平的结果。两组的平均 DNA 加合物水平相似(P=0.62)。多变量回归分析未能显示大体积 DNA 加合物与乳腺癌之间存在任何显著关联。我们的结果不支持乳腺癌风险与环境致癌物暴露之间存在任何关联,如通过诊断前白细胞中大体积 DNA 加合物的水平来衡量。需要更大的研究,使用不同的方法和/或生物标志物,以更好地评估特定环境致癌物在乳腺癌发生中的作用。

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