Smoking Status at Diagnosis and Colorectal Cancer Prognosis According to Tumor Lymphocytic Reaction
Smoking Status at Diagnosis and Colorectal Cancer Prognosis According to Tumor Lymphocytic Reaction
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DOI：
10.1093/jncics/pkaa040
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发表时间：
2020-10-01
影响因子：
4.4
通讯作者：
Ogino, Shuji
中科院分区：
文献类型：
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作者：
Fujiyoshi, Kenji;Chen, Yang;Ogino, Shuji
背景：吸烟与结直肠癌患者的生存不良有关，并可能潜在地抑制肿瘤微环境中的免疫反应。我们假设在诊断为结直肠癌时吸烟行为的预后关联可能因癌组织中的淋巴细胞反应模式不同而不同。方法：在两项大型前瞻性队列研究(护士健康研究和卫生专业人员随访研究)中，我们对1474例结直肠癌患者进行了4种组织病理学淋巴细胞反应类型的研究，包括肿瘤浸润性淋巴细胞(TIL)、瘤周反应、瘤周淋巴细胞反应和克罗恩样淋巴反应。利用事件结直肠癌患者的协变量数据，采用逆概率加权多变量COX比例风险回归模型校正组织可获得性和潜在混杂因素的选择偏差，这些混杂因素包括肿瘤分化程度、疾病分期、微卫星不稳定状态、CpG岛甲基化表型、长分布核苷酸元素-1甲基化以及KRAS、BRAF和PIK3CA突变。结果：诊断时吸烟状况与预后的关系因TIL状况而异。与从不吸烟的人相比，在TIL阴性或低TIL的肿瘤中，现有吸烟者的多变量调整后的结直肠癌特异性死亡风险比为1.50(95%可信区间=1.10~2.06)，在TIL中等或高的肿瘤中(双边P交互作用=0.009)，多变量调整后的结直肠癌特异性死亡风险比为0.43(95%可信区间=0.16~1.12)。在其他类型的淋巴细胞反应中没有观察到有统计学意义的相互作用。结论：对于TIL阴性或低TIL的癌症，确诊时吸烟状况与结直肠癌死亡率的相关性可能更强，这表明吸烟和淋巴细胞反应在结直肠癌微环境中存在潜在的相互作用。
Background: Smoking has been associated with worse colorectal cancer patient survival and may potentially suppress the immune response in the tumor microenvironment. We hypothesized that the prognostic association of smoking behavior at colorectal cancer diagnosis might differ by lymphocytic reaction patterns in cancer tissue. Methods: Using 1474 colon and rectal cancer patients within 2 large prospective cohort studies (Nurses' Health Study and Health Professionals Follow-up Study), we characterized 4 patterns of histopathologic lymphocytic reaction, including tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral lymphocytic reaction, and Crohn's-like lymphoid reaction. Using covariate data of 4420 incident colorectal cancer patients in total, an inverse probability weighted multivariable Cox proportional hazards regression model was conducted to adjust for selection bias due to tissue availability and potential confounders, including tumor differentiation, disease stage, microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Results: The prognostic association of smoking status at diagnosis differed by TIL status. Compared with never smokers, the multivariable-adjusted colorectal cancer-specific mortality hazard ratio for current smokers was 1.50 (95% confidence interval = 1.10 to 2.06) in tumors with negative or low TIL and 0.43 (95% confidence interval = 0.16 to 1.12) in tumors with intermediate or high TIL (2-sided P-interaction = .009). No statistically significant interactions were observed in the other patterns of lymphocytic reaction. Conclusions: The association of smoking status at diagnosis with colorectal cancer mortality may be stronger for carcinomas with negative or low TIL, suggesting a potential interplay of smoking and lymphocytic reaction in the colorectal cancer microenvironment.