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Cancer. 2017 Nov 1;123(21):4130-4138. doi: 10.1002/cncr.30831. Epub 2017 Jul 12.

Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

Author information

1
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
2
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, Florida.
3
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.
4
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.
5
Department of Statistics, Ohio State University, Columbus, Ohio.
6
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
7
Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.
8
Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
9
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
10
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
11
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
12
Department of Histopathology, St. James's Hospital and Trinity College Dublin Medical School, Dublin, Ireland.
13
Koch Institute for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts.
14
Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.

Abstract

BACKGROUND:

Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer.

METHODS:

Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression.

RESULTS:

Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10-4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25).

CONCLUSIONS:

This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society.

KEYWORDS:

body mass index; chromatin modification; chromatin remodeling; gene expression; obesity; prostate cancer; prostate cancer-specific mortality

PMID:
28700821
PMCID:
PMC5802874
DOI:
10.1002/cncr.30831
[Indexed for MEDLINE]
Free PMC Article

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