Sakoda Lori C, Ferrara Assiamira, Achacoso Ninah S, Peng Tiffany, Ehrlich Samantha F, Quesenberry Charles P, Habel Laurel A
Division of Research, Kaiser Permanente Northern California, Oakland, California.
Cancer Prev Res (Phila). 2015 Feb;8(2):174-9. doi: 10.1158/1940-6207.CAPR-14-0291.
Methodologic biases may explain why observational studies examining metformin use in relation to lung cancer risk have produced inconsistent results. We conducted a cohort study to further investigate this relationship, accounting for potential biases. For 47,351 patients with diabetes ages ≥40 years, who completed a health-related survey administered between 1994 and 1996, data on prescribed diabetes medications were obtained from electronic pharmacy records. Follow-up for incident lung cancer occurred from January 1, 1997, until June 30, 2012. Using Cox regression, we estimated lung cancer risk associated with new use of metformin, along with total duration, recency, and cumulative dose (all modeled as time-dependent covariates), adjusting for potential confounding factors. During 428,557 person-years of follow-up, 747 patients were diagnosed with lung cancer. No association was found with duration, dose, or recency of metformin use and overall lung cancer risk. Among never smokers, however, ever use was inversely associated with lung cancer risk [HR, 0.57; 95% confidence interval (CI), 0.33-0.99], and risk appeared to decrease monotonically with longer use (≥5 years: HR, 0.48; 95% CI, 0.21-1.09). Among current smokers, corresponding risk estimates were >1.0, although not statistically significant. Consistent with this variation in effect by smoking history, longer use was suggestively associated with lower adenocarcinoma risk (HR, 0.69; 95% CI, 0.40-1.17), but higher small cell carcinoma risk (HR, 1.82; 95% CI, 0.85-3.91). In this population, we found no evidence that metformin use affects overall lung cancer risk. The observed variation in association by smoking history and histology requires further confirmation.
方法学偏倚可能解释了为何关于二甲双胍使用与肺癌风险关系的观察性研究结果不一致。我们进行了一项队列研究，以进一步调查这种关系，并考虑潜在偏倚。对于1994年至1996年间完成健康相关调查的47351名年龄≥40岁的糖尿病患者，从电子药房记录中获取了处方糖尿病药物的数据。对肺癌发病的随访从1997年1月1日持续至2012年6月30日。使用Cox回归，我们估计了与新使用二甲双胍相关的肺癌风险，以及总疗程、近期使用情况和累积剂量（均建模为时间依赖性协变量），并对潜在混杂因素进行了调整。在428557人年的随访期间，747名患者被诊断为肺癌。未发现二甲双胍使用的疗程、剂量或近期使用情况与总体肺癌风险之间存在关联。然而，在从不吸烟者中，曾经使用二甲双胍与肺癌风险呈负相关[风险比（HR），0.57；95%置信区间（CI），0.33 - 0.99]，且随着使用时间延长（≥5年：HR，0.48；95% CI，0.21 - 1.09）风险似乎单调下降。在当前吸烟者中，相应的风险估计值>1.0，尽管无统计学意义。与这种因吸烟史导致的效应差异一致，使用时间较长与腺癌风险降低（HR，0.69；95% CI，0.40 - 1.17）有提示性关联，但与小细胞癌风险升高（HR，1.82；95% CI，0.85 - 3.91）有关。在该人群中，我们没有发现证据表明二甲双胍使用会影响总体肺癌风险。观察到的因吸烟史和组织学不同而产生的关联差异需要进一步证实。
