CORRESPONDENCE

RESPONSE: Re: Insulin-Like Growth Factor-I (IGF-I) and IGF Binding Protein-3 as Predictors of Advanced-Stage Prostate Cancer

June M. Chan

Correspondence to: June M. Chan, Sc.D., Department of Epidemiology and Biostatistics and Urology, University of California, 3333 California St., Ste. 280, San Francisco, CA 94118 (e-mail: jchan{at}epi.ucsf.edu).

We recently reported a strong, statistically significant association between serum insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) and subsequent risk of advanced-stage prostate cancer in a nested case–control study in the Physicians’ Health Study (relative risk [RR] = 5.1, 95% confidence interval [CI] 2.0 to 13.2 for IGF-I; RR = 0.2, 95% CI = 0.1 to 0.6 for IGFBP-3, comparing highest versus lowest quartiles) (1). In contrast, Dr. Lehrer and colleagues observed no correlation between serum IGF-I levels and increasing tumor stage among 114 men with prostate cancer. Furthermore, they did not observe any difference in mean level of IGF-I between the 114 men with prostate cancer and 12 men with benign prostatic hypertrophy. They conclude that "serum IGF-I levels are not related to advanced-stage prostate cancer."

It is important to note several differences between these two reports that may explain any apparent discrepancies: 1) Our blood samples were collected long before diagnosis of prostate cancer (average time from blood collection to prostate cancer diagnosis among the case patients = 9 years). In contrast, Lehrer et al. assayed serum collected after diagnosis. The actions of IGF-I and IGFBP-3 may vary at different times in the course of tumor development. This difference is evident in Table 4 from our paper, where the relative risks were stronger among men diagnosed later in the follow-up. 2) We compared levels of IGF-I and IGFBP-3 among 530 men who subsequently developed prostate cancer with that of 534 men who did not develop prostate cancer in the following 13 years. The results of Lehrer et al. are based on case–case comparisons and just 12 patients with benign prostatic hypertrophy, providing inadequate power to study this association. 3) Our assays were conducted in two waves, and the intra-assay coefficients of variation were very good for both waves (4.9% and 6.5% for IGF-I in waves 1 and 2, respectively). Lehrer et al. did not report any quality control data for their assays; nondifferential measurement error tends to bias associations to the null and could also partially explain any apparent lack of association.

Thus, these results suggest that IGF-I and IGFBP-3 play different roles in prostate cancer development at different times. Specifically, IGF may be related to an increased risk for the development of prostate cancer rather than act as a marker for the presence of tumor. The results of Lehrer et al. are not necessarily in conflict with ours. Our results indicate that serum IGF-I and IGFBP-3 may predict future risk of advanced stage prostate cancer several years before any clinical evidence of disease.

NOTES

The study design and methods employed in this investigation of the Physicians’ Health Study were reviewed and approved by the Human Research Committee of Brigham and Women’s Hospital.

REFERENCES

1 Chan JM, Stampfer MJ, Ma J, Gann P, Gaziano JM, Pollak M, et al. Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. J Natl Cancer Inst 2002;94:1099–106.[Abstract/Free Full Text]



             
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