Dybdahl M, Frentz G, Vogel U, Wallin H, Nexø B A
National Institute of Occupational Health, Copenhagen, Denmark.
Mutat Res. 1999 Jan 26;433(1):15-22. doi: 10.1016/s0921-8777(98)00057-3.
We have studied DNA repair in patients with psoriasis aiming at investigating the importance of repair in chemically induced cancer. An increased risk of non-melanoma skin cancer has been observed in psoriasis patients extensively treated with tar, methotrexate and photochemotherapy (psoralen + UVA). We measured the DNA repair capacity (DRC) by a host cell reactivation (HCR) assay in lymphocytes from psoriasis patients with and without basal cell cancer and non-psoriatic persons with and without basal cell cancer (4 x 20 study persons). Among psoriasis patients we observed a significant lower DRC in patients with skin cancer compared to patients without skin cancer (P = 0.015; Mann-Whitney, one-sided). Using the median of the healthy control group (group 4) as a cutoff value to divide the psoriasis patients into groups of high and low repair, we found that individuals who had a low repair capacity had a 6.4-fold increased skin cancer risk compared to individuals with high repair (95% confidence interval (CI), 1.44-28.5). The level of DNA repair was correlated with the age at which the psoriasis patients got their first skin cancer. The lower the level of DNA repair, the earlier the psoriasis patients had their first skin tumor (P = 0.070 Spearman; one-sided). Psoriasis patients without BCC had marginally higher repair than healthy controls (P = 0.11, Mann-Whitney, two-sided). We found no difference between BCC patients without psoriasis and healthy controls. In conclusion, these findings suggest a protective role of DNA repair in a predominantly chemically induced cancer.
我们对银屑病患者的DNA修复进行了研究,旨在调查修复在化学诱导癌症中的重要性。在接受焦油、甲氨蝶呤和光化学疗法(补骨脂素+紫外线A)广泛治疗的银屑病患者中,观察到非黑色素瘤皮肤癌的风险增加。我们通过宿主细胞再激活(HCR)试验,测量了患有和未患有基底细胞癌的银屑病患者以及患有和未患有基底细胞癌的非银屑病患者(4×20名研究对象)淋巴细胞中的DNA修复能力(DRC)。在银屑病患者中,我们观察到患有皮肤癌的患者与未患皮肤癌的患者相比,DRC显著降低(P = 0.015;Mann-Whitney,单侧)。以健康对照组(第4组)的中位数作为临界值,将银屑病患者分为高修复组和低修复组,我们发现修复能力低的个体患皮肤癌的风险比修复能力高的个体高6.4倍(95%置信区间(CI),1.44 - 28.5)。DNA修复水平与银屑病患者首次患皮肤癌的年龄相关。DNA修复水平越低,银屑病患者首次出现皮肤肿瘤的时间越早(P = 0.070,Spearman;单侧)。没有基底细胞癌的银屑病患者的修复能力略高于健康对照组(P = 0.11,Mann-Whitney,双侧)。我们发现没有银屑病的基底细胞癌患者与健康对照组之间没有差异。总之,这些发现表明DNA修复在主要由化学诱导的癌症中具有保护作用。