Discovering plasma proteins associated with breast cancer incidence in postmenopausal women in the Atherosclerosis Risk in Communities study

危险系数 乳腺癌 欧洲癌症与营养前瞻性调查 入射(几何) 前瞻性队列研究 比例危险模型 医学 肿瘤科 队列 癌症 人口 内科学 史诗 置信区间 内分泌学 物理 光学 艺术 环境卫生 文学类
作者
Maria‐Eleni Syleouni,Corinne E. Joshu,Josef Coresh,Marc J. Gunter,Kenneth R. Butler,David Couper,Marcela Guevara,Jiayun Lu,Anna E. Prizment,Elio Ríboli,Meng Ru,Yahya Mahamat‐Saleh,Karl Smith‐Byrne,Mehrnoosh M. Soori,Kala Visvanathan,Vernon A. Burk,Ziqiao Wang,Nilanjan Chatterjee,Sabine Rohrmann,Elizabeth A. Platz
出处
期刊:Journal of the National Cancer Institute [Oxford University Press]
卷期号:117 (10): 2044-2052 被引量:2
标识
DOI:10.1093/jnci/djaf170
摘要

Abstract Background Plasma proteomic data can be used to discover breast cancer risk biomarkers beyond established risk factors. Discovery using a large-scale platform in a diverse population is needed. Methods We investigated 4712 plasma proteins and breast cancer risk among postmenopausal women in a prospective cohort analysis in the Atherosclerosis Risk in Communities study. Proteins were measured by SomaScan 5K Assay. Incident cases were ascertained primarily from state cancer registries. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox regression adjusting for risk factors and applied the Benjamini-Hochberg method to control false discovery. We determined whether the statistically significant proteins were confirmed in a case-cohort study within the European Prospective Investigation into Cancer and Nutrition. Results After median follow-up of 23.3 years, 340 of 4403 women had an incident breast cancer. Two proteins were statistically significantly associated after P value adjustment: per doubling, the hazard ratio of breast cancer was 1.45 (95% CI = 1.23 to 1.70; P = 7.47*10−6, Padjusted = .0370) for protein LEG1 homolog and 2.52 (95% CI = 1.66 to 3.83; P = 1.50*10−5, Padjusted = 0.0371) for adenosine diphosphate (ADP)–dependent glucokinase. Results were consistent in a lagged analysis and among Black (28.1%) and White women. In the European Prospective Investigation into Cancer and Nutrition, both associations were confirmed (protein LEG1 homolog: HR = 1.24, 95% CI = 1.14 to 1.35; P = 9.79*10−7; ADP–dependent glucokinase: HR = 1.13, 95% CI = 1.03 to 1.23; P = .01). Conclusion We identified 2 plasma proteins associated with increased breast cancer risk over the longer term in postmenopausal women; both were confirmed in an independent cohort. If further validated, these plasma protein biomarkers could be considered for utility in current risk stratification tools.
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