Friedman Gary D, Asgari Maryam M, Warton E Margaret, Chan James, Habel Laurel A
Division of Research, Kaiser Permanente Medical Care Program, Oakland, California, USA.
Arch Intern Med. 2012 Sep 10;172(16):1246-51. doi: 10.1001/archinternmed.2012.2754.
In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other commonly used antihypertensive drugs.
In a comprehensive medical care program, we evaluated prescriptions dispensed and cancer occurrence from August 1, 1994, to February 29, 2008. We identified 712 patients with lip cancer (cases) and 22,904 comparison individuals (controls) matched for age, sex, and cohort year of entry in the susceptible group, non-Hispanic whites. We determined use, at least 2 years before diagnosis or control index date, of the commonly prescribed diuretics hydrochlorothiazide and hydrochlorothiazide combined with triamterene, the angiotensin-converting enzyme inhibitor lisinopril, the calcium channel blocker nifedipine, and the β-adrenergic blocker atenolol, the only nonphotosensitizer agent studied. We analyzed the use of each drug exclusively and regardless of use of the others, and focused on duration of use. Conditional logistic regression was used for analysis of matched case-control sets, with control for cigarette smoking.
At least a 5-year supply of a drug yielded the following odds ratios (95% CIs), respectively, compared with no use: hydrochlorothiazide, 4.22 (2.82-6.31); hydrochlorothiazide-triamterene, 2.82 (1.74-4.55); lisinopril, 1.42 (0.95-2.13); nifedipine, 2.50 (1.29-4.84); and atenolol, 1.93 (1.29-2.91). When the other drugs were excluded, the odds ratio for atenolol was reduced to 0.54 (0.07-4.08).
These data support an increased risk of lip cancer in non-Hispanic whites receiving treatment for hypertension with long-term use of photosensitizing drugs.
在筛查药物的潜在致癌作用时，我们注意到唇癌风险与具有光敏性的抗高血压药物氢氯噻嗪和硝苯地平之间存在关联。在本研究中，我们进一步明确了这些药物以及其他常用抗高血压药物与唇癌风险之间的关系。
在一项综合医疗保健项目中，我们评估了1994年8月1日至2008年2月29日期间发放的处方及癌症发生情况。我们确定了712例唇癌患者（病例组）和22,904名对照个体（对照组），这些对照个体在年龄、性别以及进入易感组（非西班牙裔白人）的队列年份方面与病例组相匹配。我们确定了在诊断或对照索引日期前至少2年使用常用利尿剂氢氯噻嗪、氢氯噻嗪与氨苯蝶啶联用、血管紧张素转换酶抑制剂赖诺普利、钙通道阻滞剂硝苯地平以及β-肾上腺素能阻滞剂阿替洛尔（唯一研究的非光敏性药物）的情况。我们分别分析了每种药物的使用情况，且不考虑其他药物的使用情况，并重点关注使用时长。采用条件逻辑回归分析匹配的病例对照数据集，并对吸烟情况进行了控制。
与未使用药物相比，至少使用5年的药物产生的比值比（95%置信区间）分别为：氢氯噻嗪，4.22（2.82 - 6.31）；氢氯噻嗪 - 氨苯蝶啶，2.82（1.74 - 4.55）；赖诺普利，1.42（0.95 - 2.13）；硝苯地平，2.50（1.29 - 4.84）；阿替洛尔，1.93（1.29 - 2.91）。当排除其他药物时，阿替洛尔的比值比降至0.54（0.07 - 4.08）。
这些数据支持了在非西班牙裔白人中，长期使用光敏性药物治疗高血压会增加患唇癌的风险。
