Association between Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk: A Prospective, Case–Cohort Study of Postmenopausal Women

Kim, Sangmi; Taylor, Jack A.; Milne, Ginger L.; Sandler, Dale P.

doi:10.1158/1940-6207.capr-13-0040

Cited by 44 publications

(45 citation statements)

References 48 publications

(54 reference statements)

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“…A recent case-cohort study nested within the Sister Study cohort reported a positive association between urinary PGE-M and breast cancer risk among postmenopausal women who did not regularly use NSAIDs (32). However, the potential effect of body weight on the association between urinary PGE-M and breast cancer risk was not evaluated.…”

Section: Discussionmentioning

confidence: 99%

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Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk

Cui

Shu

Gao

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Levels of the cyclooxygenase 2 (COX-2) enzyme are elevated in breast cancer tissue, and most COX-2 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 BMI<25 kg/m2 (P for linear 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 4 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.

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Section: Discussionmentioning

confidence: 99%

“…It has been reported that NSAID use and cigarette smoking may influence urinary levels of PGE-M (17, 32, 37). In the SWHS cohort, only a small proportion of women (< 5%) took aspirin regularly or smoked cigarettes.…”

Section: Discussionmentioning

confidence: 99%

Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk

Cui

Shu

Gao

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…[55][56][57][58] In addition, increased prostaglandin E2 metabolite in the urine is found in women who are obese and is associated with an increased risk of postmenopausal breast cancer. 59,60 This could be a consequence of increased COX-2 levels in inflamed fat. Thus, smoldering WAT inflammation and low-grade systemic inflammation are inexorably coupled, and each perpetuates the other.…”

Section: Extended Impact Of the Inflamed Microenvironmentmentioning

confidence: 99%

Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation

Iyengar

Gucalp

Dannenberg

et al. 2016

JCO

664

522

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There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. MethodsWe review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. ResultsLocally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling. Within this distinctly altered local environment, several pathophysiologic changes are found that may promote breast and other cancers. Consistently, adipose tissue inflammation is associated with a worse prognosis in patients with breast and tongue cancers. Systemically, the metabolic syndrome, including dyslipidemia and insulin resistance, occurs in the setting of adipose inflammation and operates in concert with local mechanisms to sustain the inflamed microenvironment and promote tumor growth. Importantly, adipose inflammation and its protumor consequences can be found in some individuals who are not considered to be obese or overweight by body mass index. ConclusionThe tumor-promoting effects of obesity occur at the local level via adipose inflammation and associated alterations in the microenvironment, as well as systemically via circulating metabolic and inflammatory mediators associated with adipose inflammation. Accurately characterizing the obese state and identifying patients at increased risk for cancer development and progression will likely require more precise assessments than body mass index alone. Biomarkers of adipose tissue inflammation would help to identify high-risk populations. Moreover, adipose inflammation is a reversible process and represents a novel therapeutic target that warrants further study to break the obesity-cancer link.

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“…In considering cancer risk factors, levels of urinary PGE-M are increased in both smokers and obese individuals (33,34). Moreover, several studies have already demonstrated the promise of urinary PGE-M as a cancer risk biomarker (35)(36)(37). Increased levels of urinary PGE-M have been found in both non-small cell lung cancer and colorectal cancer patients (38,39).…”

Section: Introductionmentioning

confidence: 99%

Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients

Kekatpure

Wang

et al. 2016

Cancer Prevention Research

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Cyclooxygenase-2 (COX-2)-derived prostaglandin E 2 (PGE 2 ) plays a role in the development and progression of epithelial malignancies. Measurements of urinary PGE-M, a stable metabolite of PGE 2 , reflect systemic PGE 2 levels. Here, we investigated whether urinary PGE-M levels were elevated in healthy tobacco users and in patients with oral squamous cell carcinoma (OSCC). Median urinary PGE-M levels were increased in healthy tobacco quid chewers [21.3 ng/mg creatinine (Cr); n ¼ 33; P ¼ 0.03] and smokers (32.1 ng/mg Cr; n ¼ 31; P < 0.001) compared with never tobacco quid chewers-never smokers (18.8 ng/mg Cr; n ¼ 30). Urinary PGE-M levels were also compared in OSCC patients versus healthy tobacco users. An approximately 1-fold increase in median urinary PGE-M level was found in OSCC patients (48.7 ng/mg Cr, n ¼ 78) versus healthy controls (24.5 ng/mg Cr, n ¼ 64; P < 0.001). We further determined whether baseline urinary PGE-M levels were prognostic in OSCC patients who underwent treatment with curative intent. A nearly 1-fold increase in baseline urinary PGE-M levels (64.7 vs. 33.8 ng/mg Cr, P < 0.001) was found in the group of OSCC patients who progressed (n ¼ 37) compared with the group that remained progression free (n ¼ 41). Patients with high baseline levels of urinary PGE-M had both worse disease-specific survival [HR, 1.01 per unit increase; 95% confidence interval (CI), 1.01-1.02; P < 0.001] and overall survival (HR, 1.01 per unit increase; 95% CI, 1.00-1.02; P ¼ 0.03). Taken together, our findings raise the possibility that NSAIDs, prototypic inhibitors of PGE 2 synthesis, may be beneficial for reducing the risk of tobacco-related aerodigestive malignancies or treating OSCC patients with high urinary PGE-M levels. Cancer Prev Res; 9(6); 428-36. Ó2016 AACR.

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Association between Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk: A Prospective, Case–Cohort Study of Postmenopausal Women

Cited by 44 publications

References 48 publications

Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk

Urinary Prostaglandin E2 Metabolite and Breast Cancer Risk

Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation

Elevated Levels of Urinary PGE-M Are Found in Tobacco Users and Indicate a Poor Prognosis for Oral Squamous Cell Carcinoma Patients

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