Affiliation of authors: University of Pittsburgh, Graduate School of Public Health, Pittsburgh, PA.
Correspondence to: Roberta B. Ness, M.D., M.P.H., University of Pittsburgh, Graduate School of Public Health, Rm. 517, Parran Hall, 130 DeSoto St., Pittsburgh, PA 15261.
We appreciate Dr. Balkwill's letter expanding upon our discussion of the role of inflammation in the pathogenesis of ovarian cancer (1). Dr. Balkwill presents a synopsis of data suggesting that cytokines are one type of inflammatory mediator that may potentially initiate or promote ovarian cancer. We have also hypothesized that other mechanisms that come into play in the inflammatory process, including rapid DNA turnover, oxidative stress, and prostaglandins, may play some role in ovarian cancer development. We certainly agree that these mechanisms are not uniquely related to ovarian cancer. Indeed, our hypothesis drew on the thinking by Ames et al. (2), who suggested that inflammation underlies carcinogenesis in general. Our paper provided specific epidemiologic and some basic biologic support for a relationship between inflammation and ovarian carcinogenesis.
The presence of cytokines, e.g., tumor necrosis factor- (TNF-
) in already
developed ovarian tumors cannot be taken as evidence that cytokines cause ovarian tumors, since
tumor development almost surely results in an inflammatory response. However, the fact that
mice deficient in TNF-
do not develop skin cancers suggests that, at least for that tumor
type, cytokines are important factors in carcinogenesis. We do not believe that any of the
experiments to which Dr. Balkwill refers can clearly distinguish between tumor initiation and
tumor promotion. Nor does this body of evidence preclude a role for oxidation, genetic damage,
etc., in tumor initiation. However, Dr. Balkwill's experiments add fuel to our fire and
support our call for further work along this line of inquiry.
REFERENCES
1
Ness RB, Cottreau C. Possible role of ovarian epithelial
inflammation in ovarian cancer. J Natl Cancer Inst 1999;91:1459-67.
2 Ames BN, Gold LS, Willett WC. The causes and prevention of cancer. Proc Natl Acad Sci U S A 1995;92:5258-65.[Abstract]
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