口腔癌前病變患者之自體抗體、貧血、補血素缺乏及高同型半胱氨酸血症研究

Autoantibodies, anemia, hematinic deficiencies, and hyperhomocysteinemia in oral precancer patients

吳昱學(Yu-Hsueh Wu)

指導教授 ： 陳信銘

共同指導教授 ： 江俊斌 ； 孫安迪

國立臺灣大學/醫學院/臨床牙醫學研究所/博士(2019年)

https://doi.org/10.6342/NTU201904253

摘要

背景/目的：先前研究發現許多口腔黏膜疾病的患者，部分會有貧血、補血質缺乏、血清自體抗體陽性與高同半胱胺酸血症之情形。本研究的目的為量測並比較131位口腔癌前病變的患者，是否比健康對照組有較多貧血、補血質缺乏、血清自體抗體陽性與高同半胱胺酸血症之情形。

方法：量測並比較131位口腔癌前病變患者(包含96位白斑患者，26位紅白斑患者，9位疣狀增生患者)與131位年齡、性別配對之對照組個體，其全血檢查、血清鐵、維生素B12、葉酸、同半胱氨酸（homocysteine）、胃壁細胞抗體(gastric parietal cell, GPCA)、甲狀腺球蛋白抗體(thyroglobulin antibody, TGA)、和甲狀腺微粒體抗體(thyroid microsomal antibody, TMA)等項目的差異。

結果：我們發現131位口腔癌前病變患者的血清中，有較高的頻率出現 GPCA (10.7% vs. 2.3%，P = 0.012，具顯著性差異)、TGA (4.6% vs. 2.3%，P = 0.498)與TMA (8.4% vs. 2.3%，P = 0.054，邊際顯著性差異) 陽性。同時，也發現有1位 (0.8%)、 6位 (4.6%)及16位(12.2%)口腔癌前病變患者的血清中，分別出現三種(GPCA+TGA+TMA)、兩種(GPCA+TGA, GPCA+TMA或TGA+TMA)及單種(GPCA, TGA, TMA)自體抗體。其中，測量10 位TGA/TMA陽性的患者其血清中促甲狀腺激素(thyroid-stimulating hormone, TSH)的濃度，發現有80%、10%及10%的患者分別出現正常、過低與過高的情形。我們還發現26位每天抽超過20支菸的患者，其血清中GPCA陽性率明顯高於每天抽少於20支菸的61名吸菸者（P = 0.008）。此外，我們也發現131名口腔癌前病變患者的平均血清鐵（女性）、維生素B12及葉酸的濃度顯著性較低，而血清同半胱氨酸的平均濃度則高於健康對照組（P < 0.05）。並且，這131名口腔癌前病變患者的血紅素（3.1％）、維生素B12（43.5％）及葉酸（46.6％）缺乏的頻率與高同半胱氨酸血症（22.1％）的頻率，則顯著高於健康對照組（P < 0.05）。進一步比較87名吸菸者的血清葉酸平均濃度，發現其平均值低於44名無吸菸者（P = 0.002），而26位每天抽超過20支菸的患者，血清葉酸平均濃度低於每天吸菸量小於20支的61位患者（P = 0.024），52位有嚼檳榔習慣的患者，血清葉酸平均濃度亦低於79位沒有嚼檳榔習慣的患者（P = 0.051，邊際顯著性差異）。

結論：131名口腔癌前病變患者中，約有17.6％具有血清GPCA/TGA/TMA陽性之情形。只有約20％的TGA/TMA陽性口腔癌前病變患者，有甲狀腺功能減退或甲狀腺功能亢進之情形。131名口腔癌前病變患者的貧血、血清維生素B12、葉酸缺乏以及高同半胱氨酸血症的發生的頻率，皆顯著高於健康對照組個體。

關鍵字

口腔癌前病變 ； 胃壁細胞抗體 ； 甲狀腺球蛋白抗體 ； 甲狀腺過氧化?抗體 ； 鐵 ； 維生素B12 ； 葉酸

並列摘要

Background/Purpose: Previous studies found relatively higher frequencies of autoantibodies, anemia, hematinic deficiencies, and hyperhomocysteinemia in patients with different types of oral mucosal diseases. The purpose of this study evaluated whether 131 patients with oral precancerous lesions (oral precancer patients) had significantly higher frequencies of autoantibodies, anemia, hematinic deficiencies, and hyperhomocysteinemia than 131 healthy control subjects.

Methods: The serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), thyroid microsomal antibody (TMA) levels, complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 131 oral precancer patients including 96 oral leukoplakia, 26 oral erythroleukoplakia, and 9 oral verrucous hyperplasia patients and in 131 age- and sex-matched healthy control subjects were measured and compared.

Results: We found that 131 oral precancer patients had higher frequencies of serum GPCA (10.7% vs. 2.3%, P = 0.012, statistically significant), TGA (4.6% vs. 2.3%, P = 0.498), and TMA (8.4% vs. 2.3%, P = 0.054, marginal significance) positivities than 131 healthy control subjects. We also found that 1 (0.8%), 6 (4.6%), and 16 (12.2%) oral precancer patients had the presence of three (GPCA+TGA+TMA), two (GPCA+TGA, GPCA+TMA, or TGA+TMA), or one (GPCA only, TGA only, or TMA only) autoantibody in their sera, respectively. Of 10 TGA/TMA-positive oral precancer patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 80%, 10%, and 10% of these 10 TGA/TMA-positive oral precancer patients had normal, lower, and higher serum TSH levels, respectively. We also discovered a significantly higher GPCA positive rate in 26 smokers consuming > 20 cigarettes per day than in 61 smokers consuming ≤ 20 cigarettes per day (P = 0.008). In addition, we demonstrated significantly lower mean serum iron (for women only), vitamin B12, and folic acid levels and a significantly higher mean serum homocysteine level in 131 oral precancer patients than in 131 healthy control subjects (all P-values < 0.05). Moreover, 131 oral precancer patients had significantly higher frequencies of blood hemoglobin (3.1%), vitamin B12 (43.5%), and folic acid (46.6%) deficiencies and hyperhomocysteinemia (22.1%) than 131 healthy control subjects (all P-values < 0.05). Of 131 oral precancer patients, lower mean serum folic acid levels were found in 87 cigarette smokers than in 44 non-smokers (P = 0.002), in 26 smokers consuming > 20 cigarettes per day than in 61 smokers consuming ≤ 20 cigarettes per day (P = 0.024), and in 52 betel quid chewers than in 79 non-chewers (P = 0.051, marginal significance).

Conclusions: Approximately 17.6% of 131 oral precancer patients have serum GPCA/TGA/TMA positivity. Only approximately 20% of TGA/TMA-positive oral precancer patients have either hypothyroidism or hyperthyroidism. There are significantly higher frequencies of anemia, serum vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in 131 oral precancer patients than in 131 healthy control subjects.

並列關鍵字

Oral precancer ； gastric parietal cell antibody ； thyroglobulin antibody ； thyroid microsomal antibody ； iron ； vitamin B12 ； folic acid

參考文獻

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