Inflammation and endometrial cancer: a hypothesis.
Endometrial cancer is the most common gynecologic malignancy in the United States. Substantial epidemiologic data implicate an imbalance of estrogens and progestogens in the etiology of this disease. We propose that inflammation also plays a role in endometrial cancer development. Emerging laboratory data suggest that elevated levels of prostaglandin E(2) may underlie the transformation of normal endometrium to neoplastic tissue and that in vitro nonsteroidal anti-inflammatory drugs may inhibit endometrial cancer cell growth. In this review, we suggest that the risk factors for endometrial cancer--unopposed estrogens, anovulation, polycystic ovary syndrome, excessive menstruation, early menarche, and late menopause--may be viewed as factors increasing the exposure of the endometrium to inflammation, whereas pregnancy and smoking, two likely protective factors, have the opposite effect. Chronic inflammation can induce rapid cell division, increasing the possibility for replication error, ineffective DNA repair, and subsequent mutations. A proinflammatory milieu can also directly increase estrogen production. Hence, inflammation may work in conjunction with or in addition to estrogen exposure in the development of endometrial cancer.
Modugno
Francesmary
F
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 516A Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261, USA. modugno+@pitt.edu
Ness
Roberta B
RB
Chen
Chu
C
Weiss
Noel S
NS
D000858:Anovulation / Q000150:complications / Q000276:immunology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D015232:Dinoprostone / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000453:epidemiology / Q000276:immunology* / Q000503:physiopathology*; D005260:Female; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008599:Menstruation Disturbances / Q000150:complications / Q000276:immunology; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000276:immunology; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015232:Dinoprostone