Moon Sam, Holley Sarah, Bodiwala Dhaval, Luscombe Christopher J, French Michael E, Liu Samson, Saxby Mark F, Jones Peter W, Fryer Anthony A, Strange Richard C
Human Genomics Research Group, Institute of Science and Technology in Medicine, Keele University Medical School, Hartshill Campus, University Hospital of North Staffordshire, Staffordshire, England.
Ann Hum Genet. 2006 Mar;70(Pt 2):226-36. doi: 10.1111/j.1529-8817.2005.00219.x.
Ultraviolet radiation (UVR) may protect against prostate cancer via a mechanism involving vitamin D. Thus, the vitamin D receptor (VDR) gene is a susceptibility candidate, though published data are discrepant. We studied the association of prostate cancer risk with five VDR single nucleotide polymorphisms (SNPs): G/A(1229) (SNP 1), A/G(3944) (SNP 2), T/C(30875) (SNP 3), C/T(48200) (SNP 4) and C/T(65013) (SNP 5), in 430 cancer and 310 benign prostatic hypertrophy (BPH) patients. The SNP 2 GG genotype frequency was lower in cancer than BPH patients (odds ratio = 0.63, 95% CI = 0.41-0.98, p = 0.039). SNPs 1 and 2, and SNPs 4 and 5, were in linkage disequilibrium. Two copies of haplotypes comprising SNPs 1-2, G-G (odds ratio = 0.63, p = 0.039), SNPs 2-3 G-C (odds ratio = 0.45, p = 0.008) and SNPs 1-2-3 G-G-C (odds ratio = 0.44, p = 0.006), but not SNPs 1-3, G-C (odds ratio = 0.81, p = 0.34), were associated with reduced risk (reference, no copies of the haplotypes). These associations were observed after stratification of subjects by extent of UVR exposure. These data show that SNP 2 GG genotype mediates prostate cancer risk, complementing studies reporting this allele is protective in malignant melanoma pathogenesis. They further suggest that published associations of risk with SNP 1 may result from linkage disequilibrium with SNP 2.
紫外线辐射（UVR）可能通过一种涉及维生素D的机制预防前列腺癌。因此，维生素D受体（VDR）基因是一个易感候选基因，尽管已发表的数据存在差异。我们研究了前列腺癌风险与五个VDR单核苷酸多态性（SNP）的关联：G/A(1229)（SNP 1）、A/G(3944)（SNP 2）、T/C(30875)（SNP 3）、C/T(48200)（SNP 4）和C/T(65013)（SNP 5），研究对象为430例癌症患者和310例良性前列腺增生（BPH）患者。SNP 2的GG基因型频率在癌症患者中低于BPH患者（优势比 = 0.63，95%置信区间 = 0.41 - 0.98，p = 0.039）。SNP 1和SNP 2，以及SNP 4和SNP 5处于连锁不平衡状态。包含SNP 1 - 2的G - G单倍型两份拷贝（优势比 = 0.63，p = 0.039）、SNP 2 - 3的G - C单倍型两份拷贝（优势比 = 0.45，p = 0.008）和SNP 1 - 2 - 3的G - G - C单倍型两份拷贝（优势比 = 0.44，p = 0.006），而非SNP 1 - 3的G - C单倍型两份拷贝（优势比 = 0.81，p = 0.34），与风险降低相关（参照，无单倍型拷贝）。这些关联在根据UVR暴露程度对受试者进行分层后观察到。这些数据表明SNP 2的GG基因型介导前列腺癌风险，补充了报道该等位基因在恶性黑色素瘤发病机制中具有保护作用的研究。它们进一步表明，已发表的风险与SNP 1的关联可能是由于与SNP 2的连锁不平衡所致。
