Bhavsar Nrupen A, Bream Jay H, Meeker Alan K, Drake Charles G, Peskoe Sarah B, Dabitao Djeneba, De Marzo Angelo M, Isaacs William B, Platz Elizabeth A
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland. Center for Learning Health Care, Duke Clinical Research Institute, Durham, North Carolina.
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2561-7. doi: 10.1158/1055-9965.EPI-14-0010. Epub 2014 Aug 22.
TH1 cytokines, such as IFNγ and TNFα, and potentially innate cytokines, such as IL6, can potentiate the immune response to tumor. Cytokines, such as IL1β, IL8, and IL10, may suppress anticancer immunity. Thus, we prospectively evaluated the association between peripheral-cytokine concentrations and prostate cancer.
We conducted an age-race matched case-control study (268 pairs) of incident prostate cancer in CLUE-II. We measured plasma IFNγ, IL10, IL12p70, IL1β, IL6, IL8, and TNFα concentrations using an ultrasensitive multiplex kit. ORs and 95% confidence intervals (CI) were calculated using conditional logistic regression.
The OR of prostate cancer decreased across quartiles of IFNγ (highest vs. lowest quartiles: OR, 0.49; 95% CI, 0.30-0.81; Ptrend = 0.006), TNFα (OR, 0.56; 95% CI, 0.33-0.96; Ptrend = 0.01), and IL6 (OR, 0.46; 95% CI, 0.26-0.79; Ptrend = 0.007). Higher TNFα (OR, 0.28; 95% CI, 0.09-0.85; Ptrend = 0.01) and IL6 (OR, 0.20; 95% CI, 0.06-0.67; Ptrend = 0.003) concentrations were associated with lower Gleason sum ≥7 disease risk. Other cytokines were not as clearly associated with risk.
Men with a prediagnostic circulating TH1 profile and higher IL6 may have a lower risk of prostate cancer, including aggressive disease. Whether this profile reflects (i) an intraprostatic immune environment in benign tissue that protects against prostate cancer, (ii) the immune milieu in response to a prostate adenocarcinoma that inhibits tumor growth and detectability, and/or (iii) a systemic immune profile that mediates the influence of modifiable factors on risk, warrants additional study.
Identifying specific inflammatory cytokines associated with prostate cancer may lead to improved prevention and treatment strategies.
TH1细胞因子，如IFNγ和TNFα，以及潜在的固有细胞因子，如IL6，可增强对肿瘤的免疫反应。细胞因子，如IL1β、IL8和IL10，可能会抑制抗癌免疫。因此，我们前瞻性地评估了外周细胞因子浓度与前列腺癌之间的关联。
我们在CLUE-II中进行了一项年龄-种族匹配的病例对照研究（268对），研究对象为新发前列腺癌患者。我们使用超灵敏多重检测试剂盒测量血浆IFNγ、IL10、IL12p70、IL1β、IL6、IL8和TNFα的浓度。使用条件逻辑回归计算比值比（OR）和95%置信区间（CI）。
前列腺癌的OR值在IFNγ的四分位数中呈下降趋势（最高四分位数与最低四分位数相比：OR，0.49；95%CI，0.30-0.81；P趋势=0.006），TNFα（OR，0.56；95%CI，0.33-0.96；P趋势=0.01）和IL6（OR，0.46；95%CI，0.26-0.79；P趋势=0.007）。较高的TNFα（OR，0.28；95%CI，0.09-0.85；P趋势=0.01）和IL6（OR，0.20；95%CI，0.06-0.67；P趋势=0.003）浓度与较低的Gleason总分≥7疾病风险相关。其他细胞因子与风险的关联不那么明显。
诊断前循环中具有TH1特征且IL6水平较高的男性患前列腺癌（包括侵袭性疾病）的风险可能较低。这种特征是否反映了（i）良性组织中防止前列腺癌的前列腺内免疫环境，（ii）对抑制肿瘤生长和可检测性的前列腺腺癌作出反应的免疫环境，和/或（iii）介导可改变因素对风险影响的全身免疫特征，值得进一步研究。
识别与前列腺癌相关的特定炎性细胞因子可能会带来更好的预防和治疗策略。
