Wang Li-E, Xiong Ping, Strom Sara S, Goldberg Leonard H, Lee Jeffrey E, Ross Merrick I, Mansfield Paul F, Gershenwald Jeffrey E, Prieto Victor G, Cormier Janice N, Duvic Madeleine, Clayman Gary L, Weber Randal S, Lippman Scott M, Amos Christopher I, Spitz Margaret R, Wei Qingyi
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
J Natl Cancer Inst. 2005 Dec 21;97(24):1822-31. doi: 10.1093/jnci/dji429.
Mutagen sensitivity, measured as mutagen-induced chromatid breaks per cell in primary lymphocytes in vitro, has been used to study susceptibility to various epithelial cancers. Patients with xeroderma pigmentosum are highly sensitive to ultraviolet (UV) light due to inherited defects in DNA repair and have a 1000-fold higher risk of UV-induced skin cancer than the general population. However, an association between UV-induced chromosomal aberrations and risk of skin cancer in the general population has not been established.
We assessed in vitro UVB-induced chromatid breaks in a hospital-based case-control study. The study included 469 patients with skin cancer (231 with nonmelanoma skin cancer [NMSC] and 238 with cutaneous malignant melanoma [CMM]) and 329 cancer-free control subjects. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two-sided.
Compared with the frequency of UVB-induced chromatid breaks per cell in control subjects (mean = 0.28 breaks per cell, 95% CI = 0.27 to 0.30), that in NMSC patients (basal cell carcinoma [BCC], n = 143, mean = 0.36 breaks per cell, 95% CI = 0.33 to 0.39 and squamous cell carcinoma [SCC], n = 88, mean = 0.35 breaks per cell, 95% CI = 0.32 to 0.38) was higher (P = .001 and P < .001, respectively), but that in CMM case patients (mean = 0.30 breaks per cell, 95% CI = 0.28 to 0.33) was not (P = .22). A frequency of chromatid breaks per cell above the median of control subjects was associated with nearly threefold increased risks for BCC (OR = 2.78, 95% CI = 1.79 to 4.30) and SCC (OR = 2.62, 95% CI = 1.50 to 4.60), but not with an increased risk of CMM. A dose-response relationship was evident between mutagen sensitivity and risk for both BCC (Ptrend < .001) and SCC (Ptrend < .001). Multiplicative interactions between mutagen sensitivity and sun exposure variables on risk, particularly for sunburn in BCC and hair color, tanning ability, and family history of skin cancer in SCC, were seen for NMSC but not CMM.
UVB-induced mutagen sensitivity may play a role in susceptibility to NMSC but not to CMM.
诱变敏感性通过体外原代淋巴细胞中诱变剂诱导的每个细胞的染色单体断裂数来衡量，已被用于研究对各种上皮癌的易感性。着色性干皮病患者由于DNA修复存在遗传性缺陷，对紫外线（UV）高度敏感，患紫外线诱导的皮肤癌的风险比普通人群高1000倍。然而，普通人群中紫外线诱导的染色体畸变与皮肤癌风险之间的关联尚未确立。
在一项基于医院的病例对照研究中，我们评估了体外中波紫外线（UVB）诱导的染色单体断裂情况。该研究纳入了469例皮肤癌患者（231例非黑素瘤皮肤癌[NMSC]患者和238例皮肤恶性黑色素瘤[CMM]患者）以及329例无癌对照者。采用多变量逻辑回归计算比值比（OR）和95%置信区间（CI）。所有统计检验均为双侧检验。
与对照者每个细胞中UVB诱导的染色单体断裂频率（平均值=每个细胞0.28次断裂，95%CI=0.27至0.30）相比，NMSC患者（基底细胞癌[BCC]，n=143，平均值=每个细胞0.36次断裂，95%CI=0.33至0.39；鳞状细胞癌[SCC]，n=88，平均值=每个细胞0.35次断裂，95%CI=0.32至0.38）的频率更高（P分别为0.001和P<0.001），但CMM病例患者（平均值=每个细胞0.30次断裂，95%CI=0.28至0.33）并非如此（P=0.22）。每个细胞的染色单体断裂频率高于对照者中位数与BCC（OR=2.78，95%CI=1.79至4.30）和SCC（OR=2.62，95%CI=1.50至4.60）风险增加近三倍相关，但与CMM风险增加无关。诱变敏感性与BCC（Ptrend<0.001）和SCC（Ptrend<0.001）风险之间均存在明显的剂量反应关系。在NMSC患者中观察到诱变敏感性与日晒变量对风险的相乘交互作用，特别是BCC中的晒伤以及SCC中的头发颜色、晒黑能力和皮肤癌家族史，但在CMM患者中未观察到。
UVB诱导的诱变敏感性可能在NMSC易感性中起作用，但在CMM易感性中不起作用。
