Warkentin Matthew T, Tammemägi Martin C, Freedman Matthew T, Ragard Lawrence R, Hocking William G, Kvale Paul A, Brenner Darren R, Hu Ping, Riley Thomas L, Commins John, Church Timothy R, Berg Christine D
Department of Health Sciences, Brock University, St. Catharine's, Ontario, Canada.
Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, Alberta, Canada.
JNCI Cancer Spectr. 2018 Jan 31;2(1):pkx010. doi: 10.1093/jncics/pkx010. eCollection 2018 Jan.
A small proportion of non-small cell lung cancers (NSCLCs) have been observed to spread to distant lymph nodes (N3) or metastasize (M1) or both, while the primary tumor is small (≤3 cm, T1). These small aggressive NSCLCs (SA-NSLSC) are important as they are clinically significant, may identify unique biologic pathways, and warrant aggressive follow-up and treatment. This study identifies factors associated with SA-NSCLC and attempts to validate a previous finding that women with a family history of lung cancer are at particularly elevated risk of SA-NSCLC.
This study used a case-case design within the National Cancer Institute's National Lung Screening Trial (NLST) cohort. Case patients and "control" patients were selected based on TNM staging parameters. Case patients (n = 64) had T1 NSCLCs that were N3 or M1 or both, while "control" patients (n = 206) had T2 or T3, N0 to N2, and M0 NSCLCs. Univariate and multivariable logistic regression were used to identify factors associated with SA-NSCLC.
In bootstrap bias-corrected multivariable logistic regression models, small aggressive adenocarcinomas were associated with a positive history of emphysema (odds ratio [OR] = 5.15, 95% confidence interval [CI] = 1.63 to 23.00) and the interaction of female sex and a positive family history of lung cancer (OR = 6.55, 95% CI = 1.06 to 50.80).
Emphysema may play a role in early lung cancer progression. Females with a family history of lung cancer are at increased risk of having small aggressive lung adenocarcinomas. These results validate previous findings and encourage research on the role of female hormones interacting with family history and genetic factors in lung carcinogenesis and progression.
已观察到一小部分非小细胞肺癌（NSCLC）在原发肿瘤较小（≤3 cm，T1）时就已扩散至远处淋巴结（N3）或发生转移（M1）或两者皆有。这些侵袭性小的NSCLC（SA - NSCLC）很重要，因为它们具有临床意义，可能识别出独特的生物学途径，并且需要积极的随访和治疗。本研究确定与SA - NSCLC相关的因素，并试图验证先前的一项发现，即有肺癌家族史的女性患SA - NSCLC的风险特别高。
本研究在国立癌症研究所的国家肺癌筛查试验（NLST）队列中采用病例 - 病例设计。根据TNM分期参数选择病例患者和“对照”患者。病例患者（n = 64）患有T1期NSCLC且伴有N3或M1或两者皆有，而“对照”患者（n = 206）患有T2或T3期、N0至N2期且M0期的NSCLC。采用单因素和多因素逻辑回归来确定与SA - NSCLC相关的因素。
在经自抽样偏差校正的多因素逻辑回归模型中，侵袭性小的腺癌与肺气肿阳性病史（比值比[OR] = 5.15，95%置信区间[CI] = 1.63至23.00）以及女性性别与肺癌家族史阳性的相互作用（OR = 6.55，95% CI = 1.06至50.80）相关。
肺气肿可能在早期肺癌进展中起作用。有肺癌家族史的女性患侵袭性小的肺腺癌的风险增加。这些结果验证了先前的发现，并鼓励对女性激素与家族史和遗传因素相互作用在肺癌发生和进展中的作用进行研究。
