Wake Forest University Health Sciences, Department of Cancer Biology, Winston-Salem, NC, USA.
Cancer Biol Ther. 2010 Jun 15;9(12):994-9. doi: 10.4161/cbt.9.12.11689. Epub 2010 Jun 4.
Prospective epidemiologic studies indicate that the risk for advanced prostate cancer is increased among men with high levels of serum calcium. Because serum calcium levels are influenced by the calcium-sensing receptor (CaSR), we examined prostate cancer in African-American men in relation to three single nucleotide polymorphisms (SNPs) in the CaSR gene, A986S, R990G and Q1011E. This is the first study of CaSR polymorphisms and risk of prostate cancer.
The CaSR genotypes were not associated with prostate cancer overall. However, we observed significant heterogeneity by disease stage for the Q1011E polymorphism (p = 0.02). Advanced cases were significantly less likely than controls or localized cases to be homozygous for the minor allele of the Q1011E polymorphism (1 vs. 5%). Cases with advanced disease were six times less likely to carry two copies of the minor allele than were controls (OR = 0.16, p = 0.02) or localized cases (OR = 0.15, p = 0.01) and were significantly older at diagnosis (68.8 ± 5.7 vs. 64.0 ± 9.0 y for the QQ and EE genotypes, p = 0.004).
We genotyped three CaSR SNPs for 458 African-American prostate cancer cases and 248 controls from a population-based case-control study, the California Collaborative Prostate Cancer Study.
The CaSR Q1011E minor allele, which is common in populations with African ancestry, may be associated with a less aggressive form of prostate cancer among African-American men.
前瞻性流行病学研究表明,血清钙水平高的男性患晚期前列腺癌的风险增加。由于血清钙水平受钙敏感受体(CaSR)的影响,我们研究了非洲裔美国男性的前列腺癌与 CaSR 基因中的三个单核苷酸多态性(SNP)之间的关系,即 A986S、R990G 和 Q1011E。这是首次研究 CaSR 多态性与前列腺癌风险的关系。
CaSR 基因型与前列腺癌总体无关。然而,我们观察到 Q1011E 多态性与疾病分期存在显著的异质性(p = 0.02)。与对照组或局限性病例相比,晚期病例纯合子携带 Q1011E 多态性的次要等位基因的可能性显著降低(1 比 5%)。与对照组(OR = 0.16,p = 0.02)或局限性病例(OR = 0.15,p = 0.01)相比,携带两个次要等位基因的晚期病例的可能性要小 6 倍,且诊断时年龄明显更大(68.8 ± 5.7 比 QQ 和 EE 基因型的 64.0 ± 9.0 岁,p = 0.004)。
我们对来自基于人群的病例对照研究——加利福尼亚合作前列腺癌研究中的 458 例非洲裔美国前列腺癌病例和 248 例对照进行了三个 CaSR SNP 的基因分型。
CaSR Q1011E 次要等位基因在具有非洲血统的人群中很常见,可能与非洲裔美国男性中侵袭性较弱的前列腺癌形式有关。