Gross Neil D, Boyle Jay O, Morrow Jason D, Williams Myles K, Moskowitz Chaya S, Subbaramaiah Kotha, Dannenberg Andrew J, Duffield-Lillico Anna J
Department of Surgery (Head and Neck Service), Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Clin Cancer Res. 2005 Aug 15;11(16):6087-93. doi: 10.1158/1078-0432.CCR-05-0733.
Increased levels of cyclooxygenase-2 and prostaglandin E2 (PGE2) have been observed in tobacco-related malignancies of the upper aerodigestive tract. Moreover, exposure to tobacco smoke can stimulate the synthesis of PGE2. Recent evidence suggests that urinary PGE metabolite (PGE-M) can be used as an index of systemic PGE2 production. In this study, we investigated whether levels of urinary PGE-M were increased in smokers and in patients with head and neck squamous cell carcinoma (HNSCC).
Fifty-eight HNSCC cases and 29 age- and gender-matched healthy controls were prospectively enrolled in the study. A detailed smoking history and single void urine specimen were obtained from each participant. Levels of urinary PGE-M were quantified in a blinded fashion using mass spectrometry and compared with smoking history and tumor status.
Adjusted for case-control matching, median urinary PGE-M levels were significantly higher in ever smokers (15.7 ng/mg creatinine) compared with never smokers (9.9 ng/mg creatinine) for the entire study population (n = 87, P = 0.005). Concentrations of urinary PGE-M were nearly doubled in ever smokers (15.2 ng/mg creatinine) versus never smokers (7.8 ng/mg creatinine) among healthy controls (P = 0.001). Higher PGE-M levels were observed in current versus former smokers and in those with greater pack-year exposure. A significant difference in amounts of PGE-M was not observed in patients with HNSCC versus healthy controls.
Increased levels of urinary PGE-M were observed in smokers. Urinary PGE-M may have use as a noninvasive biomarker of the effects of tobacco smoke exposure.
在上呼吸道和消化道的烟草相关恶性肿瘤中,已观察到环氧合酶 -2 和前列腺素 E2(PGE2)水平升高。此外,接触烟草烟雾可刺激 PGE2 的合成。最近的证据表明,尿 PGE 代谢物(PGE-M)可作为全身 PGE2 产生的指标。在本研究中,我们调查了吸烟者和头颈部鳞状细胞癌(HNSCC)患者的尿 PGE-M 水平是否升高。
前瞻性纳入 58 例 HNSCC 病例和 29 例年龄及性别匹配的健康对照者进行研究。从每位参与者处获取详细的吸烟史和单次晨尿标本。采用质谱法以盲法对尿 PGE-M 水平进行定量,并与吸烟史和肿瘤状态进行比较。
对病例对照匹配进行调整后,在整个研究人群(n = 87,P = 0.005)中,曾经吸烟者的尿 PGE-M 中位数水平(15.7 ng/mg 肌酐)显著高于从不吸烟者(9.9 ng/mg 肌酐)。在健康对照者中,曾经吸烟者的尿 PGE-M 浓度(15.2 ng/mg 肌酐)几乎是从不吸烟者(7.8 ng/mg 肌酐)的两倍(P = 0.001)。当前吸烟者与既往吸烟者相比以及吸烟包年数更多者中观察到更高的 PGE-M 水平。HNSCC 患者与健康对照者之间未观察到 PGE-M 量的显著差异。
吸烟者尿 PGE-M 水平升高。尿 PGE-M 可能用作烟草烟雾暴露影响的非侵入性生物标志物。