The Association of Modifiable Breast Cancer Risk Factors and Somatic Genomic Alterations in Breast Tumors: The Cancer Genome Atlas Network
The Association of Modifiable Breast Cancer Risk Factors and Somatic Genomic Alterations in Breast Tumors: The Cancer Genome Atlas Network
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DOI：
10.1158/1055-9965.epi-19-1087
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发表时间：
2020-03-01
影响因子：
3.8
通讯作者：
Kraft, Peter
中科院分区：
文献类型：
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作者：
Heng, Yujing J.;Hankinson, Susan E.;Kraft, Peter
背景：可改变的乳腺癌危险因素与肿瘤基因组改变之间的联系在很大程度上尚未探索。我们评估了诊断前体重指数（BMI）、吸烟和饮酒与体细胞拷贝数变异（SCNV）、总体细胞突变负荷（TSMB）、7个单碱基取代（SBS）标记的相关性。（SBS1、SBS2、SBS3、SBS5、SBS13、SBS29和SBS30）和9个驱动突变方法：从TCGA数据库中检索临床和基因组数据。从四个TCGA站点（n = 219名女性）收集风险因素信息，包括BMI（诊断前1年），吸烟（吸烟者/非吸烟者）和饮酒（当前饮酒者/非饮酒者）。在所有肿瘤中进行多变量回归分析，并根据雌激素受体（ER）状态分层。结果：在所有女性（P = 0.039）和ER肿瘤女性（P = 0.031）中，BMI增加与SCNV增加相关。吸烟者的SCNV和TSMB高于非吸烟者（P <0.05）。饮酒者的SCNV高于不饮酒者（P <0.05）. SBS3（基于缺陷性同源重组的修复）仅在患有ER疾病的饮酒者中发现。GATA3基因突变发生在BMI较高的女性中。没有关联是显着的多重测试correction.Conclusions后：这项研究提供了初步证据表明，BMI，吸烟，饮酒可以影响乳腺肿瘤生物学，特别是DNA的改变。影响：这项研究证明了可改变的乳腺癌风险因素与肿瘤基因组改变之间的联系。
Background: The link between modifiable breast cancer risk factors and tumor genomic alterations remains largely unexplored. We evaluated the association of prediagnostic body mass index (BMI), cigarette smoking, and alcohol consumption with somatic copy number variation (SCNV), total somatic mutation burden (TSMB), seven single base substitution (SBS) signatures (SBS1, SBS2, SBS3, SBS5, SBS13, SBS29, and SBS30), and nine driver mutations (CDH1, GATA3, KMT2C, MAP2K4, MAP3K1, NCOR1, PIK3CA, RUNX1, and TP53) in a subset of The Cancer Genome Atlas (TCGA).Methods: Clinical and genomic data were retrieved from the TCGA database. Risk factor information was collected from four TCGA sites (n = 219 women), including BMI (1 year before diagnosis), cigarette smoking (smokers/nonsmokers), and alcohol consumption (current drinkers/nondrinkers). Multivariable regression analyses were conducted in all tumors and stratified according to estrogen receptor (ER) status.Results: Increasing BMI was associated with increasing SCNV in all women (P = 0.039) and among women with ER- tumors (P = 0.031). Smokers had higher SCNV and TSMB versus nonsmokers (P < 0.05 all women). Alcohol drinkers had higher SCNV versus nondrinkers (P < 0.05 all women and among women with ER- tumors). SBS3 (defective homologous recombination-based repair) was exclusively found in alcohol drinkers with ER- disease. GATA3 mutation was more likely to occur in women with higher BMI. No association was significant after multiple testing correction.Conclusions: This study provides preliminary evidence that BMI, cigarette smoking, and alcohol consumption can influence breast tumor biology, in particular, DNA alterations. Impact: This study demonstrates a link between modifiable breast cancer risk factors and tumor genomic alterations.