TY - JOUR
T1 - Visualization and Quantification of the Association Between Breast Cancer and Cholesterol in the All of Us Research Program
AU - Feng, Jianglin
AU - Symonds, Esteban Astiazaran
AU - Karnes, Jason H.
N1 - Funding Information:
This work was supported by grants from the Japan Society for the Promotion of Science (JSPS) Grants‐in‐Aid for Scientific Research: Nos. JP16H06313, JP22H00585 (K.A.), JP16H03842, JP21K18324, JP22H02199, JP21H04954 (Y.S.), and JP21J13562 (R.M.). This work was also supported by a grant from Core Research for Evolutional Science and Technology, Japan Science and Technology Agency: No. JPMJCR17H2. The authors thank Edanz ( https://jp.edanz.com/ac ) for editing a draft of this paper.
Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work and the University of Arizona - Banner Health All of Us Research Program is supported by OT2OD026549 from the National Institutes of Health’s Office of the Director. JHK is supported by the NIH’s National Heart, Lung, and Blood Institute (NHLBI, K01HL143137, R01 HL158686, R01 HL156993). The All of Us Research Program is supported by the National Institutes of Health, Office of the Director: Regional Medical Centers: 1 OT2 OD026549; 1 OT2 OD026554; 1 OT2 OD026557; 1 OT2 OD026556; 1 OT2 OD026550; 1 OT2 OD 026552; 1 OT2 OD026553; 1 OT2 OD026548; 1 OT2 OD026551; 1 OT2 OD026555; IAA #: AOD 16037; Federally Qualified Health Centers: HHSN 263201600085U; Data and Research Center: 5 U2C OD023196; Biobank: 1 U24 OD023121; The Participant Center: U24 OD023176; Participant Technology Systems Center: 1 U24 OD023163; Communications and Engagement: 3 OT2 OD023205; 3 OT2 OD023206; and Community Partners: 1 OT2 OD025277; 3 OT2 OD025315; 1 OT2 OD025337; 1 OT2 OD025276. In addition, the All of Us Research Program would not be possible without the partnership of its participants.
Publisher Copyright:
© The Author(s) 2023.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Epidemiologic evidence for the association of cholesterol and breast cancer is inconsistent. Several factors may contribute to this inconsistency, including limited sample sizes, confounding effects of antihyperlipidemic treatment, age, and body mass index, and the assumption that the association follows a simple linear function. Here, we aimed to address these factors by combining visualization and quantification a large-scale contemporary electronic health record database (the All of Us Research Program). We find clear visual and quantitative evidence that breast cancer is strongly, positively, and near-linearly associated with total cholesterol and low-density lipoprotein cholesterol, but not associated with triglycerides. The association of breast cancer with high-density lipoprotein cholesterol was non-linear and age dependent. Standardized odds ratios were 2.12 (95% confidence interval 1.9-2.48), P = 5.6 × 10−31 for total cholesterol; 1.99 (1.75-2.26), P = 2.6 × 10−26 for low-density lipoprotein cholesterol; 1.69 (1.3-2.2), P = 9.0 × 10−5 for high-density lipoprotein cholesterol at age < 56; and 0.65 (0.55-0.78), P = 1.2 × 10−6 for high-density lipoprotein cholesterol at age ⩾ 56. The inclusion of the lipid levels measured after antihyperlipidemic treatment in the analysis results in erroneous associations. We demonstrate that the use of the logistic regression without inspecting risk variable linearity and accounting for confounding effects may lead to inconsistent results.
AB - Epidemiologic evidence for the association of cholesterol and breast cancer is inconsistent. Several factors may contribute to this inconsistency, including limited sample sizes, confounding effects of antihyperlipidemic treatment, age, and body mass index, and the assumption that the association follows a simple linear function. Here, we aimed to address these factors by combining visualization and quantification a large-scale contemporary electronic health record database (the All of Us Research Program). We find clear visual and quantitative evidence that breast cancer is strongly, positively, and near-linearly associated with total cholesterol and low-density lipoprotein cholesterol, but not associated with triglycerides. The association of breast cancer with high-density lipoprotein cholesterol was non-linear and age dependent. Standardized odds ratios were 2.12 (95% confidence interval 1.9-2.48), P = 5.6 × 10−31 for total cholesterol; 1.99 (1.75-2.26), P = 2.6 × 10−26 for low-density lipoprotein cholesterol; 1.69 (1.3-2.2), P = 9.0 × 10−5 for high-density lipoprotein cholesterol at age < 56; and 0.65 (0.55-0.78), P = 1.2 × 10−6 for high-density lipoprotein cholesterol at age ⩾ 56. The inclusion of the lipid levels measured after antihyperlipidemic treatment in the analysis results in erroneous associations. We demonstrate that the use of the logistic regression without inspecting risk variable linearity and accounting for confounding effects may lead to inconsistent results.
KW - Breast cancer
KW - antihyperlipidemic treatment
KW - electronic medical records
KW - high-density lipoprotein cholesterol
KW - low-density lipoprotein cholesterol
KW - total cholesterol
KW - triglycerides
UR - http://www.scopus.com/inward/record.url?scp=85146278381&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85146278381&partnerID=8YFLogxK
U2 - 10.1177/11769351221144132
DO - 10.1177/11769351221144132
M3 - Article
AN - SCOPUS:85146278381
SN - 1176-9351
VL - 22
JO - Cancer Informatics
JF - Cancer Informatics
ER -