Abstract
Mutations in the p53 gene are among the most frequent genetic events in human cancer and may be triggered by environmental and occupational exposures. We examined the association of clinical and pathological characteristics of breast tumors and breast cancer risk factors according to the prevalence and type of p53 mutations. Using tumor blocks from incident cases from a case–control study in western New York, we screened for p53 mutations in exons 2–11 using the Affymetrix p53 Gene Chip array and analyzed case–case comparisons using logistic regression. The p53 mutation frequency among cases was 28.1 %; 95 % were point mutations (13 % of which were silent) and the remainder were single base pair deletions. Sixty seven percent of all point mutations were transitions; 24 % of them are G:C>A:T at CpG sites. Positive p53 mutation status was associated with poorer differentiation (OR, 95 % CI 2.29, 1.21–4.32), higher nuclear grade (OR, 95 % CI 1.99, 1.22–3.25), and increased Ki-67 status (OR, 95 % CI 1.81, 1.10–2.98). Cases with P53 mutations were more likely to have a combined ER-positive and PR-negative status (OR, 95 % CI 1.65, 1.01–2.71), and a combined ER-negative and PR-negative status (OR, 95 % CI 2.18, 1.47–3.23). Body mass index >30 kg/m2, waist circumference >79 cm, and waist-to-hip ratio >0.86 were also associated with p53 status; obese breast cancer cases are more likely to have p53 mutations (OR, 95 % CI 1.78, 1.19–2.68). We confirmed that p53 mutations are associated with less favorable tumor characteristics and identified an association of p53 mutation status and adiposity.
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This work was funded by DOD Breast Cancer Research Program (DAMD 179616202, DAMD 17030446) and United States Public Health Service (USPHS) Grant Numbers K07CA136969 and R01CA092040 from the National Cancer Institute and P50-AA09802 from the National Institute on Alcohol Abuse and Alcoholism. These studies were conducted in part at the Lombardi Comprehensive Cancer Center Histopathology & Tissue Shared resource which is supported in part by NIH/NCI Grant P30-CA051008. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.
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Heather M. Ochs-Balcom and Catalin Marian have contributed equally to this work.
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Ochs-Balcom, H.M., Marian, C., Nie, J. et al. Adiposity is associated with p53 gene mutations in breast cancer. Breast Cancer Res Treat 153, 635–645 (2015). https://doi.org/10.1007/s10549-015-3570-5
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DOI: https://doi.org/10.1007/s10549-015-3570-5