Department of Human Sciences/Kinesiology, The Ohio State University College of Education and Human Ecology, Columbus, OH, USA.
The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Int J Oncol. 2015 Oct;47(4):1537-44. doi: 10.3892/ijo.2015.3141. Epub 2015 Aug 31.
Chronic inflammation plays an important role in lung carcinogenesis. Few prospective studies have examined associations between lung cancer, serum C-reactive protein (CRP), a measure of systemic inflammation, and inflammatory lifestyle factors, such as smoking and obesity. This study prospectively examined the relationship between CRP and lung cancer death and its interrelationships with several lifestyle factors. Baseline data on smoking and other lifestyle variables were collected for 8,950 participants in the Third National Health and Nutrition Examination Survey (NHANES III: 1988-1994). Baseline CRP levels were measured in serum samples by nephelometry. Mortality status was ascertained through probabilistic record matching using the National Death Index through 2006. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for CRP and lung cancer death, with adjustment for smoking and other variables. During 18 years of follow-up, 219 individuals died from lung cancer. Multivariate regression models revealed a dose-response effect for elevated CRP and risk of lung cancer death when adjusting for age, gender, BMI and smoking. Compared to individuals with CRP <3 mg/l, lung cancer death was significantly associated with elevated levels of CRP: HR=1.63 (95% CI=1.15-2.26) for 3-7 mg/l and HR=2.44 (95% CI=1.81‑3.45) for CRP >7 mg/l, P-trend <0.0001). The risk of lung cancer death for smokers increased 9-fold in adjusted models (P<0.0001). When stratified by gender and smoking status the effects of CRP were similar for smokers and males but did not reach statistical significance for females and non-smokers. This study supports a dose-dependent relationship between lung cancer death and CRP for males and smokers, but additional efforts are needed to better elucidate these relationships in women and non-smokers. The results suggest that CRP may emerge as a valuable tool in identifying high-risk subgroups of smokers for lung cancer prevention strategies.
慢性炎症在肺癌的发生发展中起着重要作用。很少有前瞻性研究探讨过肺癌、血清 C 反应蛋白（CRP）——一种全身性炎症的衡量指标，以及吸烟和肥胖等炎症生活方式因素之间的关联。本研究前瞻性地研究了 CRP 与肺癌死亡之间的关系及其与几种生活方式因素的相互关系。在第三次全国健康和营养调查（NHANES III：1988-1994 年）中，对 8950 名参与者收集了吸烟和其他生活方式变量的基线数据。采用散射比浊法测量血清样本中的 CRP 水平。通过使用国家死亡索引进行概率记录匹配，确定了截至 2006 年的死亡率状态。使用 Cox 比例风险回归模型，在调整吸烟和其他变量后，估计 CRP 与肺癌死亡的危险比（HR）。在 18 年的随访期间，有 219 人死于肺癌。多变量回归模型显示，在调整年龄、性别、BMI 和吸烟因素后，CRP 升高与肺癌死亡的风险呈剂量反应关系。与 CRP<3mg/l 的个体相比，CRP 升高与肺癌死亡显著相关：3-7mg/l 时 HR=1.63（95%CI=1.15-2.26），CRP>7mg/l 时 HR=2.44（95%CI=1.81-3.45），P-趋势<0.0001）。在调整模型中，吸烟者患肺癌死亡的风险增加了 9 倍（P<0.0001）。按性别和吸烟状况分层后，CRP 的影响在吸烟者和男性中相似，但在女性和非吸烟者中没有达到统计学意义。本研究支持男性和吸烟者肺癌死亡与 CRP 之间存在剂量依赖性关系，但需要进一步努力更好地阐明女性和非吸烟者中这些关系。结果表明，CRP 可能成为识别肺癌预防策略高危吸烟人群的有用工具。
