Influence of KRAS mutations, persistent organic pollutants, and trace elements on survival from pancreatic ductal adenocarcinoma.
Influence of KRAS mutations, persistent organic pollutants, and trace elements on survival from pancreatic ductal adenocarcinoma.
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DOI：
10.1016/j.envres.2020.109781
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发表时间：
2020-11
影响因子：
8.3
通讯作者：
PANKRAS II Study Group
中科院分区：
文献类型：
--
作者：
Porta M;Pumarega J;Amaral AFS;Genkinger JM;Camargo J;Mucci L;Alguacil J;Gasull M;Zhang X;Morales E;Iglesias M;Ogino S;Engel LS;PANKRAS II Study Group
胰腺导管腺癌（PDAC）持续生存率低的原因仅部分已知。以前没有研究分析过KRAS突变，持久性有机污染物（POP）和微量元素对PDAC或任何其他人类癌症生存期的综合影响。分析KRAS突变、持久性有机污染物和微量元素对PDAC生存率的单独和联合影响。事件的PDAC（n = 185）的情况下，在西班牙东部的五家医院在1992年至1995年进行了前瞻性的确定，并在住院期间进行了面对面的采访。通过聚合酶链反应和人工限制性片段长度多态性从肿瘤组织中确定KRAS突变状态。治疗前采集血液和趾甲样本。采用电子捕获检测的高分辨率气相色谱法分析了持久性有机污染物的血清浓度。采用电感耦合等离子体质谱法测定了趾甲样品中12种微量元素的含量。多变量考克斯比例风险回归用于评估预后相关性。KRAS突变肿瘤患者的早期死亡风险比KRAS野生型PDAC患者高70%（风险比[HR] = 1.7，p = 0.026），调整了年龄，性别和肿瘤分期。KRAS突变状态仅与生存率适度相关，当进一步调整治疗或治疗意图时，无统计学显著性。当考虑到KRAS突变状态时，治疗的有益效果保持不变，并且治疗在KRAS突变肿瘤患者亚组中的有效性似乎并没有降低。持久性有机污染物没有实质性影响生存：调整后的人力资源的最高持久性有机污染物的三分之一是接近统一的所有持久性有机污染物。当考虑POP和KRAS对生存期的联合影响时，KRAS突变肿瘤患者的HR为中度和不显著（大多数HR约为1.3至1.4）。较高浓度的铅、镉、砷、钒和铝与较好的存活率相关。当KRAS状态、持久性有机污染物和微量元素与治疗同时沿着考虑时，只有后者与生存率具有统计学显著相关性。在这项基于分子、临床和环境流行病学的研究中，当同时考虑治疗时，KRAS突变状态、持久性有机污染物和微量元素与PDAC生存率无不良关系;只有治疗与生存率独立相关。在诊断时测量的持久性有机污染物和金属没有不良预后影响，这为此类接触对PDAC患者生存的影响提供了科学和临床保证。与KRAS突变的弱相关性导致对PDAC中高度频繁的遗传改变的临床意义的了解不足。
Reasons why pancreatic ductal adenocarcinoma (PDAC) continues to have poor survival are only partly known. No previous studies have analyzed the combined influence of KRAS mutations, persistent organic pollutants (POPs), and trace elements upon survival in PDAC or in any other human cancer. To analyze the individual and combined influence of KRAS mutations, POPs, and trace elements upon survival from PDAC. Incident cases of PDAC (n = 185) were prospectively identified in five hospitals in Eastern Spain in 1992–1995 and interviewed face-to-face during hospital admission. KRAS mutational status was determined from tumour tissue through polymerase chain reaction and artificial restriction fragment length polymorphism. Blood and toenail samples were obtained before treatment. Serum concentrations of POPs were analyzed by high-resolution gas chromatography with electron-capture detection. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Multivariable Cox proportional hazards regression was used to assess prognostic associations. Patients with a KRAS mutated tumor had a 70% higher risk of early death than patients with a KRAS wild-type PDAC (hazard ratio [HR] = 1.7, p = 0.026), adjusting for age, sex, and tumor stage. KRAS mutational status was only modestly and not statistically significantly associated with survival when further adjusting by treatment or by treatment intention. The beneficial effects of treatment remained unaltered when KRAS mutational status was taken into account, and treatment did not appear to be less effective in the subgroup of patients with a KRAS mutated tumor. POPs did not materially influence survival: the adjusted HR of the highest POP tertiles was near unity for all POPs. When considering the joint effect on survival of POPs and KRAS, patients with KRAS mutated tumors had modest and nonsignificant HRs (most HRs around 1.3 to 1.4). Higher concentrations of lead, cadmium, arsenic, vanadium, and aluminium were associated with better survival. When KRAS status, POPs, and trace elements were simultaneously considered along with treatment, only the latter was statistically significantly related to survival. In this study based on molecular, clinical, and environmental epidemiology, KRAS mutational status, POPs, and trace elements were not adversely related to PDAC survival when treatment was simultaneously considered; only treatment was independently related to survival. The lack of adverse prognostic effects of POPs and metals measured at the time of diagnosis provide scientific and clinical reassurance on the effects of such exposures upon survival of patients with PDAC. The weak association with KRAS mutations contributes to the scant knowledge on the clinical implications of a genetic alteration highly frequent in PDAC.
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影响因子：
28.2
作者：
Collisson EA;Trejo CL;Silva JM;Gu S;Korkola JE;Heiser LM;Charles RP;Rabinovich BA;Hann B;Dankort D;Spellman PT;Phillips WA;Gray JW;McMahon M
通讯作者：
McMahon M
影响因子：
8.8
作者：
Eser, S.;Schnieke, A.;Schneider, G.;Saur, D.
通讯作者：
Saur, D.
影响因子：
3.8
作者：
Carrigan, Patricia E.;Hentz, Joseph G.;Miller, Laurence J.
通讯作者：
Miller, Laurence J.
影响因子：
9.3
作者：
Brychta, Nora;Krahn, Thomas;von Ahsenh, Oliver
通讯作者：
von Ahsenh, Oliver
影响因子：
1.6
作者：
Carrato A;Falcone A;Ducreux M;Valle JW;Parnaby A;Djazouli K;Alnwick-Allu K;Hutchings A;Palaska C;Parthenaki I
通讯作者：
Parthenaki I