Wong Jason Y Y, Bassig Bryan A, Loftfield Erikka, Hu Wei, Freedman Neal D, Ji Bu-Tian, Elliott Paul, Silverman Debra T, Chanock Stephen J, Rothman Nathaniel, Lan Qing
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
JNCI Cancer Spectr. 2019 Dec 12;4(2):pkz102. doi: 10.1093/jncics/pkz102. eCollection 2020 Apr.
The contribution of measurable immunological and inflammatory parameters to lung cancer development remains unclear, particularly among never smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK).
We evaluated 424 407 adults aged 37-73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered and collected at baseline in 2006-2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference.
There were 1493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was statistically significantly associated with elevated lung cancer risk (HR = 1.67, 95% CI = 1.41 to 1.98). Among women, increased risks were found in current smokers ( / = 244 / 19 464, HR = 2.15, 95% CI = 1.46 to 3.16), former smokers ( / = 280 / 69 198, HR = 1.75, 95% CI = 1.24 to 2.47), and never smokers without environmental tobacco smoke exposure (n / n = 108 / 111 294, HR = 1.93, 95% CI = 1.11 to 3.35). Among men, stronger associations were identified in current smokers (n / = 329 / 22 934, HR = 2.95, 95% CI = 2.04 to 4.26) and former smokers ( / = 358/71 616, HR = 2.38, 95% CI = 1.74 to 3.27) but not in never smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions.
Elevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men.
可测量的免疫和炎症参数对肺癌发生的作用仍不明确,尤其是在从不吸烟者中。我们调查了英国全血细胞计数和分类白细胞计数与肺癌发病风险之间的关系,以及按吸烟状况和性别定义的亚组中的关系。
我们评估了英国生物银行中424407名年龄在37 - 73岁之间的成年人。2006 - 2010年在基线时进行问卷调查、体格测量并采集血液。使用标准方法测量全血细胞计数。从癌症登记处获取肺癌诊断和组织学分类信息。多变量Cox回归模型用于估计全血细胞计数和亚型特异性计数四分位数(Q)与肺癌发病的风险比(HR)及95%置信区间,以Q1作为参照。
在平均7年的随访期间共诊断出1493例肺癌病例。总体而言,全血细胞计数最高四分位数与肺癌风险升高在统计学上显著相关(HR = 1.67,95% CI = 1.41至1.98)。在女性中,现吸烟者(n / N = 244 / 19464,HR = 2.15,95% CI = 1.46至3.16)、既往吸烟者(n / N = 280 / 69198,HR = 1.75,95% CI = 1.24至2.47)以及无环境烟草烟雾暴露的从不吸烟者(n / N = 108 / 111294,HR = 1.93,95% CI = 1.11至3.35)的肺癌风险增加。在男性中,现吸烟者(n / N = 329 / 22934,HR = 2.95,95% CI = 2.04至4.26)和既往吸烟者(n / N = 358 / 71616,HR = 2.38,95% CI = 1.74至3.27)的关联更强,但从不吸烟者中未发现关联。肺腺癌和鳞状细胞癌的结果相似,主要由中性粒细胞比例升高所致。
白细胞升高可能是肺癌风险增加的众多重要标志物之一,尤其是在从不吸烟的女性和曾经吸烟的男性中。