Han Jiali, Cox David G, Colditz Graham A, Hunter David J
Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Mol Carcinog. 2006 Sep;45(9):694-700. doi: 10.1002/mc.20190.
The p53 gene is involved in the control of cell-cycle arrest and apoptosis. The germline Arg72Pro polymorphism alters the protein's biochemical functions, and may confer individual susceptibility to skin cancer. We evaluated the association of the Arg72Pro polymorphism with skin cancer risk among Caucasians in a nested case-control study within the Nurses' Health Study (NHS) (219 melanoma, 286 squamous cell carcinoma (SCC), and 300 basal cell carcinoma (BCC) and 874 controls). Compared to the Arg/Arg genotype, the Pro/Pro genotype had an OR of 1.57 (95%CI, 0.81-3.06) for melanoma risk, and an OR of 1.79 (95%CI, 1.01-3.17) for BCC risk. The positive association of the Pro allele with BCC risk was only limited to women with two or fewer lifetime sunburns (P, trend, 0.002; P, interaction, 0.02). No association was observed between the polymorphism and SCC risk. We also observed that the Pro allele was inversely associated with the risk of childhood sunburn among Caucasian participants pooled from four nested case-control studies within the NHS. This study suggests that the Arg72Pro polymorphism may play a role in skin carcinogenesis.
p53基因参与细胞周期停滞和细胞凋亡的调控。种系中的Arg72Pro多态性改变了该蛋白的生化功能,并可能使个体易患皮肤癌。在护士健康研究(NHS)的一项巢式病例对照研究中,我们评估了白种人中Arg72Pro多态性与皮肤癌风险之间的关联(219例黑色素瘤、286例鳞状细胞癌(SCC)、300例基底细胞癌(BCC)和874例对照)。与Arg/Arg基因型相比,Pro/Pro基因型患黑色素瘤风险的比值比(OR)为1.57(95%可信区间,0.81 - 3.06),患BCC风险的OR为1.79(95%可信区间,1.01 - 3.17)。Pro等位基因与BCC风险的正相关仅局限于一生中晒伤次数为两次或更少的女性(P趋势,0.002;P交互作用,0.02)。未观察到该多态性与SCC风险之间存在关联。我们还观察到,在从NHS内四项巢式病例对照研究汇总的白种人参与者中,Pro等位基因与儿童期晒伤风险呈负相关。这项研究表明,Arg72Pro多态性可能在皮肤癌发生过程中起作用。