DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer
DNA repair capacity of lymphoblastoid cell lines from sisters discordant for breast cancer
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DOI：
10.1093/jnci/dji013
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发表时间：
2005-01-19
影响因子：
10.3
通讯作者：
Santella, RM
中科院分区：
文献类型：
--
作者：
Kennedy, DO;Agrawal, M;Santella, RM
背景：DNA 修复能力的个体差异可能会影响癌症风险。我们通过分析姐妹对来测试乳腺癌病例患者的核苷酸切除修复途径是否存在缺陷。方法：从纽约大都会乳腺癌家庭登记处获得来自乳腺癌不一致姐妹的细胞系（137 个家庭，其中包括 158 名病例患者和 154 名对照姐妹）。将类淋巴母细胞用苯并[a]芘二醇环氧化合物 (BPDE) 处理 30 分钟，然后立即收获或洗涤并在完全培养基中培养 4 小时以进行 DNA 修复。使用多克隆抗 BPDE-DNA 一抗进行免疫荧光来定量 BPDE-DNA 加合物。 DNA 修复能力百分比的计算方法是：处理后立即染色减去修复 4 小时后染色之间的差值，除以初始损伤，并根据对照值分类为四分位数。使用根据献血年龄、体重指数和吸烟情况进行调整的条件逻辑回归模型计算优势比和 95% 置信区间 (CI)。统计检验是双面的。结果：乳腺癌病例患者的平均 DNA 修复能力百分比低于对照受试者（差异 = 8.6，95% CI = 4.3 至 13.8，P = .001）。使用 DNA 修复能力百分比最高的四分位数作为参考组，随着 DNA 修复能力下降，乳腺癌的调整后比值比从 1.23（95% CI = 0.57 至 2.65）增加到 2.38（95% CI = 1.17 至 4.86）再到 2.99（95% CI = 1.45 至 6.17）（P 趋势 = .002）。结论：DNA 修复能力缺陷与乳腺癌风险增加相关。
Background: Interindividual differences in DNA repair capacity may influence cancer risk. We tested whether the nucleotide excision repair pathway was deficient in breast cancer case patients by analyzing sister pairs. Methods: Cell lines derived from sisters discordant for breast cancer (137 families containing 158 case patients and 154 control sisters) were obtained from the Metropolitan New York Registry of Breast Cancer Families. Lymphoblastoid cells were treated with benzo[a]pyrene diolepoxide (BPDE) for 30 minutes and were either harvested immediately or were washed and cultured in complete medium for 4 hours to allow DNA repair. Immunofluorescence using a polyclonal anti-BPDE-DNA primary antibody was used to quantify BPDE-DNA adducts. Percent DNA repair capacity was calculated from the difference between staining immediately after treatment minus that after 4 hours of repair, divided by the initial damage and was categorized into quartiles based on control values. Odds ratios and 95% confidence intervals (CIs) were calculated using conditional logistic regression models adjusted for age at blood donation, body mass index, and smoking. Statistical tests were two-sided. Results: Mean percent DNA repair capacity was lower in breast cancer case patients than in control subjects (difference = 8.6, 95% CI = 4.3 to 13.8, P = .001). Using the quartile with the highest percent DNA repair capacity as the referent group, adjusted odds ratios of breast cancer increased from 1.23 (95% CI = 0.57 to 2.65) to 2.38 (95% CI = 1.17 to 4.86) to 2.99 (95% CI = 1.45 to 6.17) (P-trend = .002) as DNA repair capacity decreased. Conclusions: Deficient DNA repair capacity is associated with increased breast cancer risk.