Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk

Background: Levels of the cyclooxygenase 2 (COX2) enzyme are elevated in breast cancer tissue, and most COX2 effects are believed to be mediated through overproduction of prostaglandin E2 (PGE2). We evaluated associations between the primary urinary metabolite of PGE2 (PGE-M) and breast cancer risk. Methods: A nested case–control study of 504 cases and 1,082 controls was conducted using data from the Shanghai Women's Health Study, a large population-based prospective cohort study of 74,941 Chinese women. Urinary PGE-M was measured using a liquid chromatography/tandem mass spectrometric method. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (95% CI) with adjustment for potential confounders. Results: Overall, no association between urinary PGE-M and breast cancer was detected. However, a suggestive positive association was found among postmenopausal women. In particular, a clear dose–response relationship between urinary PGE-M and breast cancer was observed among postmenopausal women with a body mass index (BMI) < 25 kg/m2 (Plinear trend = 0.005). Among these women, risk of breast cancer increased from 1.00 (reference) to 1.06 (95% CI, 0.56–1.99), 1.50 (95% CI, 0.79–2.83), and 2.32 (95% CI, 1.24–4.41) for the lowest to highest quartiles of PGE-M, and such associations were stronger among those who were diagnosed with cancer within the first four years of sample collection. No apparent association was observed among overweight postmenopausal women (BMI ≥ 25 kg/m2). Conclusion: High urinary PGE-M level was associated with elevated risk of breast cancer among normal weight, postmenopausal women. Impact: Urinary PGE-M level may be useful for breast cancer risk assessment among normal weight, postmenopausal women. Cancer Epidemiol Biomarkers Prev; 23(12); 2866–73. ©2014 AACR.

[1]  E. Simpson,et al.  Obesity and breast cancer: role of inflammation and aromatase. , 2013, Journal of molecular endocrinology.

[2]  M. Ramos-Nino The Role of Chronic Inflammation in Obesity-Associated Cancers , 2013, ISRN oncology.

[3]  Dale P Sandler,et al.  Association between Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk: A Prospective, Case–Cohort Study of Postmenopausal Women , 2013, Cancer Prevention Research.

[4]  R. DuBois,et al.  Urinary PGE-M: A Promising Cancer Biomarker , 2013, Cancer Prevention Research.

[5]  S. H. Shirley,et al.  Transgenic insulin‐like growth factor‐1 stimulates activation of COX‐2 signaling in mammary glands , 2012, Molecular carcinogenesis.

[6]  C. Hudis,et al.  Increased levels of COX-2 and prostaglandin E2 contribute to elevated aromatase expression in inflamed breast tissue of obese women. , 2012, Cancer discovery.

[7]  R. DuBois,et al.  The role of the PGE2-aromatase pathway in obesity-associated breast inflammation. , 2012, Cancer discovery.

[8]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[9]  Priya Bhardwaj,et al.  Obesity Is Associated with Inflammation and Elevated Aromatase Expression in the Mouse Mammary Gland , 2011, Cancer Prevention Research.

[10]  X. Shu,et al.  Intra-Person Variation of Urinary Biomarkers of Oxidative Stress and Inflammation , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[11]  R. DuBois,et al.  Eicosanoids and cancer , 2010, Nature Reviews Cancer.

[12]  P. Elwood,et al.  Aspirin, salicylates, and cancer , 2009, The Lancet.

[13]  M. Etminan,et al.  Breast cancer and use of nonsteroidal anti-inflammatory drugs: a meta-analysis. , 2008, Journal of the National Cancer Institute.

[14]  P. Allavena,et al.  Cancer-related inflammation , 2008, Nature.

[15]  Louise R Howe,et al.  Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer , 2007, Breast Cancer Research.

[16]  S. Ambs,et al.  Inflammation and IGF‐I activate the Akt pathway in breast cancer , 2007, International journal of cancer.

[17]  N. Rothman,et al.  Prospective study of urinary prostaglandin E2 metabolite and colorectal cancer risk. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[18]  N. Rothman,et al.  The Shanghai Women's Health Study: rationale, study design, and baseline characteristics. , 2005, American journal of epidemiology.

[19]  J. Morrow,et al.  Levels of Prostaglandin E Metabolite, the Major Urinary Metabolite of Prostaglandin E2, Are Increased in Smokers , 2005, Clinical Cancer Research.

[20]  J. Morrow,et al.  Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer. , 2004, Analytical biochemistry.

[21]  N. Bundred,et al.  COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ , 2004, British Journal of Cancer.

[22]  C. Nishida,et al.  Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies , 2004, The Lancet.

[23]  T. Putti,et al.  Cyclooxygenase‐2 expression: a potential prognostic and predictive marker for high‐grade ductal carcinoma in situ of the breast , 2004, Histopathology.

[24]  K. Wellen,et al.  Obesity-induced inflammatory changes in adipose tissue. , 2003, The Journal of clinical investigation.

[25]  O. Watanabe,et al.  Expression of cyclooxygenase-2 in malignant and benign breast tumors. , 2003, Anticancer research.

[26]  K. Chew,et al.  Cyclooxygenase-2 expression is related to nuclear grade in ductal carcinoma in situ and is increased in its normal adjacent epithelium. , 2003, Cancer research.

[27]  A. Sahin,et al.  Cyclooxygenase-2 expression in human breast cancers and adjacent ductal carcinoma in situ. , 2002, Cancer research.

[28]  K. Subbaramaiah,et al.  PEA3 Is Up-regulated in Response to Wnt1 and Activates the Expression of Cyclooxygenase-2* , 2001, The Journal of Biological Chemistry.

[29]  T. Hla,et al.  Overexpression of Cyclooxygenase-2 Is Sufficient to Induce Tumorigenesis in Transgenic Mice* , 2001, The Journal of Biological Chemistry.

[30]  M. Taketo Cyclooxygenase-2 inhibitors in tumorigenesis (Part II). , 1998, Journal of the National Cancer Institute.

[31]  T. Luo,et al.  Aspirin use and breast cancer risk: a meta-analysis , 2011, Breast Cancer Research and Treatment.

[32]  Cancer Facts & Figures 2021 , 2010 .

[33]  M. Thun,et al.  Pharmacologic effects of NSAIDs and implications for the risks and benefits of long-term prophylactic use of aspirin to prevent cancer. , 2009, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[34]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[35]  I. M. Neiman,et al.  [Inflammation and cancer]. , 1974, Patologicheskaia fiziologiia i eksperimental'naia terapiia.