Rossing M A, Scholes D, Cushing-Haugen K L, Voigt L F
Fred Hutchinson Cancer Research Center, Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle 98109-1024, USA.
Cancer Epidemiol Biomarkers Prev. 2000 Mar;9(3):319-23.
Histamine (H2) receptor antagonists, such as cimetidine and ranitidine, became available in the late 1970s and presently number among the most commonly used drugs. Cimetidine has been hypothesized to exert a cancer preventive effect on the prostate due to its ability to inhibit the binding of dihydrotestosterone to androgen receptors. Other hormonal effects of this drug include increases in serum prolactin levels and inhibition of 2-hydroxylation of estradiol. We assessed risk of prostate and breast cancers in a cohort of 48,512 members of the Group Health Cooperative of Puget Sound prescribed cimetidine or another H2 blocker between 1977 and 1995. Standardized incidence ratios were calculated comparing the observed numbers of cancers to those expected based on population rates in western Washington State. Because cimetidine, but not other H2 blockers, influences hormonal activity and metabolism, we conducted nested case-control studies comparing cancer risk among individuals treated with cimetidine to individuals who used other H2 blockers. Risks of breast and prostate cancers were identical among users of cimetidine and users of other H2 blockers (relative risk, 1.0 for both cancers). We observed no trend in risk of breast cancer according to time since first or last cimetidine prescription or number of cimetidine prescriptions filled. For prostate cancer, our findings were similar save for a modest increase in risk among men who had filled > or =21 cimetidine prescriptions (relative risk, 1.4; 95% confidence interval, 1.0-1.9). Our results suggest that use of cimetidine does not influence risk of female breast cancer. Further, these data provide little evidence to support the previously hypothesized preventive effect of cimetidine on risk of prostate cancer.
组胺(H2)受体拮抗剂,如西咪替丁和雷尼替丁,于20世纪70年代末问世,目前是最常用的药物之一。据推测,西咪替丁因其能够抑制二氢睾酮与雄激素受体的结合而对前列腺具有癌症预防作用。该药物的其他激素作用包括血清催乳素水平升高和抑制雌二醇的2-羟化作用。我们评估了普吉特海湾健康合作组织的48512名成员在1977年至1995年间服用西咪替丁或其他H2阻滞剂后患前列腺癌和乳腺癌的风险。通过比较观察到的癌症病例数与基于华盛顿州西部人群发病率预期的病例数,计算标准化发病率比。由于西咪替丁而非其他H2阻滞剂会影响激素活性和代谢,我们进行了巢式病例对照研究,比较服用西咪替丁的个体与使用其他H2阻滞剂的个体的癌症风险。西咪替丁使用者和其他H2阻滞剂使用者患乳腺癌和前列腺癌的风险相同(两种癌症的相对风险均为1.0)。根据首次或最后一次西咪替丁处方时间或所填充的西咪替丁处方数量,我们未观察到乳腺癌风险的变化趋势。对于前列腺癌,我们的研究结果相似,但在填充≥21张西咪替丁处方的男性中风险略有增加(相对风险,1.4;95%置信区间,1.0 - 1.9)。我们的结果表明,使用西咪替丁不会影响女性乳腺癌风险。此外,这些数据几乎没有证据支持先前假设的西咪替丁对前列腺癌风险的预防作用。