Friedman Gary D, Achacoso Ninah, Habel Laurel A
Division of Research, Oakland, CA.
Department of Health Research and Policy, Stanford University School of Medicine, CA.
Perm J. 2019;23. doi: 10.7812/TPP/18-040.
Epidemiologic analyses of gabapentin use and cancer risk in Kaiser Permanente Northern California were previously carried out in a collaborative study and independently evaluated in a UK database.
To update these epidemiologic analyses with 7.5 more years of follow-up.
Case-control analyses using conditional logistic regression to estimate relative risk by odds ratios using the prior collaboration's criteria for identifying positive drug-cancer associations and our more stringent criteria requiring stronger association, lower p values, and evidence of dose response. New associations were reanalyzed with additional control for limited measures of smoking and alcohol use.
Gabapentin-cancer associations.
No previously found associations met our stringent criteria, but cancers of the mouth/pharynx, esophagus, liver, and vagina did. All odds ratios for 3 or more and 8 or more prescriptions were moderately reduced by control for smoking and alcohol. Substantial elevations of risk of mouth/pharynx, liver, and vaginal cancers were associated with only 1 prescription dispensed. Sensitivity analyses aimed at possible confounding and other biases did not change our conclusions but did reveal a markedly increased risk of vaginal cancer in gabapentin users with epilepsy compared with users without.
The reduced magnitude of relative risk with control for smoking and alcohol use suggests confounding by known risk factors. Biologically implausible elevated risk from just 1 prescription suggests confounding by indication. Either or both of these concerns applies to each of the 4 cancer sites associated with gabapentin use. Updated analyses show little if any evidence for carcinogenic effects of gabapentin.
先前在一项合作研究中对北加利福尼亚州凯撒医疗集团使用加巴喷丁与癌症风险进行了流行病学分析，并在一个英国数据库中进行了独立评估。
通过延长7.5年的随访来更新这些流行病学分析。
病例对照分析，使用条件逻辑回归通过比值比估计相对风险，采用先前合作研究中确定药物与癌症阳性关联的标准，以及我们更严格的标准，即要求更强的关联、更低的P值和剂量反应证据。对新发现的关联进行重新分析，并额外控制吸烟和饮酒的有限指标。
加巴喷丁与癌症的关联。
先前发现的关联均未达到我们的严格标准，但口腔/咽部、食管、肝脏和阴道的癌症达到了。对吸烟和饮酒进行控制后，3次及以上和8次及以上处方的所有比值比均适度降低。仅1次配方便与口腔/咽部、肝脏和阴道癌症风险的大幅升高相关。旨在评估可能的混杂因素和其他偏倚的敏感性分析并未改变我们的结论，但确实显示与无癫痫的加巴喷丁使用者相比，有癫痫的加巴喷丁使用者患阴道癌的风险显著增加。
控制吸烟和饮酒后相对风险降低，这表明存在已知风险因素的混杂作用。仅1次处方就出现生物学上不合理的风险升高，这表明存在指征混杂。这些问题中的一个或两个适用于与加巴喷丁使用相关的4个癌症部位中的每一个。更新后的分析显示，几乎没有证据表明加巴喷丁有致癌作用。
