Ramachandran S, Fryer A A, Smith A G, Lear J T, Bowers B, Hartland A J, Whiteside J R, Jones P W, Strange R C
Centre for Cell and Molecular Medicine and Department of Dermatology, North Staffordshire Hospital, Stoke-on-Trent, Staffordshire, UK.
Pharmacogenetics. 2001 Apr;11(3):247-54. doi: 10.1097/00008571-200104000-00008.
Previous studies have shown that patients who present at first or a later presentation with a cluster of new basal cell carcinoma (BCC) comprise a subgroup, termed multiple presentation phenotype (MPP), that is at increased risk of developing further lesions. In this study, we examined the hypothesis that patients who develop multiple clusters are a high-risk subgroup. We found, in a total group of 926 BCC patients, 32 patients with 2-5 BCC clusters (multiple cluster MPP) and 113 cases with only one cluster (single cluster MPP). Multiple cluster MPP cases had mean of 11.3 BCC compared with 3.7 in single cluster MPP cases during similar follow-up. Ultraviolet (UV) exposure in these groups was similar. We determined whether the multiple cluster MPP was associated with characteristics associated with sensitivity to UV or glutathione S-transferase (GST) GSTT1, GSTM1, cytochrome P450 (CYP) CYP2D6, tumour necrosis factor (TNF)-alpha and vitamin D receptor (VDR) genotypes previously associated with BCC presentational phenotypes. While the frequencies of blue eyes and male gender were greater in multiple cluster than single cluster cases, these differences were not significant. In multiple cluster cases, mean age at first presentation with single tumours occurred earlier and the frequencies of CYP2D6 extensive metabolizer (EM) (94.4%) and GSTT1 null (41.2%) were significantly greater (P = 0.028 and P = 0.004) than in single cluster cases (67.1% and 14.3%, respectively). The odds ratios for the individual associations of CYP2D6 EM and GSTT1 null with the multiple cluster MPP were relatively larger; 15.5 and 7.39, respectively. TNF-alpha and VDR genotypes were not associated with multiple cluster MPP. We propose that the MPP is not the consequence of excessive UV exposure but rather reflects the presence of a distinct BCC subgroup which is defined by combinations of risk genes.
以往的研究表明，初发或后续出现一系列新发基底细胞癌（BCC）的患者构成一个亚组，称为多发性表现型（MPP），该亚组发生更多病变的风险增加。在本研究中，我们检验了发生多个病灶群的患者是高危亚组这一假设。我们在总共926例BCC患者中发现，32例患者有2 - 5个BCC病灶群（多病灶群MPP），113例患者仅有一个病灶群（单病灶群MPP）。在相似的随访期间，多病灶群MPP病例的BCC平均数量为11.3个，而单病灶群MPP病例为3.7个。这些组中的紫外线（UV）暴露情况相似。我们确定多病灶群MPP是否与先前与BCC表现型相关的对UV或谷胱甘肽S - 转移酶（GST）GSTT1、GSTM1、细胞色素P450（CYP）CYP2D6、肿瘤坏死因子（TNF） - α和维生素D受体（VDR）基因型相关的特征有关。虽然多病灶群病例中蓝眼睛和男性的比例高于单病灶群病例，但这些差异并不显著。在多病灶群病例中，首次出现单个肿瘤时的平均年龄更早，且CYP2D6广泛代谢型（EM）（94.4%）和GSTT1缺失型（41.2%）的比例显著高于单病灶群病例（分别为67.1%和14.3%）（P = 0.028和P = 0.004）。CYP2D6 EM和GSTT1缺失型与多病灶群MPP的个体关联的优势比相对较大；分别为15.5和7.39。TNF - α和VDR基因型与多病灶群MPP无关。我们提出，MPP不是过度UV暴露的结果，而是反映了一个由风险基因组合定义的独特BCC亚组的存在。
