Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy.
Leukocyte telomere length and its association with mammographic density and proliferative diagnosis among women undergoing diagnostic image-guided breast biopsy.
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DOI：
10.1186/s12885-015-1860-2
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发表时间：
2015-10-30
期刊：
影响因子：
3.8
通讯作者：
Gierach GL
中科院分区：
文献类型：
--
作者：
Bodelon C;Heaphy CM;Meeker AK;Geller B;Vacek PM;Weaver DL;Chicoine RE;Shepherd JA;Mahmoudzadeh AP;Patel DA;Brinton LA;Sherman ME;Gierach GL
乳腺摄影密度（MD）升高是一个很强的乳腺癌风险因素，但相关机制知之甚少。高MD和乳腺癌风险可能反映了累积暴露于促进上皮细胞分裂的因素。细胞复制史的一个标志是端粒长度，但其与MD的关系尚不清楚。我们研究了端粒长度，细胞复制史的标志物，与MD和活检诊断的关系。195名年龄在40-65岁之间的女性被临床转诊到佛蒙特州的一家学术机构进行图像引导乳腺活检。采用定量聚合酶链反应测定外周血白细胞端粒相对长度（LTL）。使用乳腺密度体模，在数字乳腺X线照片中对主要诊断的对侧乳房的头尾位视图中量化MD体积，同时使用阈值软件测量MD面积（cm 2）。对数转换LTL和连续MD测量（体积和面积）之间的关联进行了评估，使用线性回归模型调整年龄和体重指数。分析按活检诊断分层：增殖性（增生、原位或浸润性癌）或非增殖性（良性或其他非增殖性良性诊断）。增生性疾病女性患者（n = 141）的平均相对LTL为1.6（SD = 0.9），而非增生性疾病女性患者（n = 54）的平均相对LTL为1.2（SD = 0.6）（P = 0.002）。平均百分比MD体积没有不同的诊断（P = 0.69）。在诊断为增殖性（P = 0.89）或非增殖性（P = 0.48）的女性中，LTL与MD无关。然而，LTL与增殖性诊断的风险显著增加相关（校正OR = 2.46，95%CI：1.47，4.42）。我们对LTL的分析没有发现与MD相关。然而，我们的研究结果表明，LTL可能是一个标记的风险，增殖病理学的妇女转介活检的基础上乳腺成像。
Elevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis. One hundred and ninety-five women, ages 40–65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm2) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses). Mean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 % CI: 1.47, 4.42). Our analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.