Yang Hannah P, Garcia-Closas Montserrat, Lacey James V, Brinton Louise A, Lissowska Jolanta, Peplonska Beta, Chanock Stephen, Gaudet Mia M
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
Cancer Epidemiol Biomarkers Prev. 2009 Feb;18(2):585-9. doi: 10.1158/1055-9965.EPI-08-0677. Epub 2009 Feb 3.
Genetic variation in the androgen receptor (AR) gene may be associated with endometrial cancer risk based on the role of AR in regulating androgen levels. However, endometrial cancer studies reported inconsistent associations for a CAG repeat polymorphism in exon 1. Only one of these studies measured haplotype-tagging single nucleotide polymorphisms (htSNP) in AR and found statistically nonsignificant, decreased associations with endometrial cancer risk. In a population-based case-control study of 497 cases and 1,024 controls, we examined the CAG repeat polymorphism and six htSNPs (rs962458, rs6152, rs1204038, rs2361634, rs1337080, and rs1337082), which cover an estimated 80% of the known common variation in AR among Caucasian populations. CAG repeat length was not significantly associated with endometrial cancer [odds ratio per unit increase in the average number of repeats, 1.02 (95% confidence interval, 0.97-1.08); P(trend) = 0.29]. Minor alleles in three correlated htSNPs (rs6152, rs1204038, and rs1337082; r(2) >0.6) were associated with increased risk for endometrial cancer. The strongest association was observed for rs6152, with the odds ratios (95% confidence interval) being 1.13 (0.89-1.44) for heterozygous and 2.40 (1.28-4.51) for homozygous minor genotypes (P(trend) = 0.02) compared with homozygous major allele genotype. However, these associations were not statistically significant after permutation adjustment for multiple comparisons (P(trend) > 0.09). Haplotype analyses did not reveal any additional associations with endometrial cancer. Results from our study, taken together with previously published studies, provide little evidence of a consistent association between common genetic variation in AR and endometrial cancer risk.
基于雄激素受体（AR）在调节雄激素水平中的作用，AR基因的遗传变异可能与子宫内膜癌风险相关。然而，关于外显子1中CAG重复多态性的子宫内膜癌研究报告的关联并不一致。这些研究中只有一项测量了AR中的单倍型标签单核苷酸多态性（htSNP），发现与子宫内膜癌风险的关联在统计学上无显著意义且呈下降趋势。在一项基于人群的病例对照研究中，我们纳入了497例病例和1,024例对照，检测了CAG重复多态性和6个htSNP（rs962458、rs6152、rs1204038、rs2361634、rs1337080和rs1337082），这些位点覆盖了白种人群中AR已知常见变异的约80%。CAG重复长度与子宫内膜癌无显著关联[平均重复次数每增加一个单位的优势比为1.02（95%置信区间为0.97 - 1.08）；P（趋势）= 0.29]。三个相关htSNP（rs6152、rs1204038和rs1337082；r(2)>0.6）中的次要等位基因与子宫内膜癌风险增加相关。rs6152的关联最强，杂合子的优势比（95%置信区间）为1.13（0.89 - 1.44），纯合子次要基因型的优势比为2.40（1.28 - 4.51）（与纯合子主要等位基因基因型相比，P（趋势）= 0.02）。然而，在对多重比较进行排列调整后，这些关联无统计学意义（P（趋势）> 0.09）。单倍型分析未发现与子宫内膜癌的其他关联。我们的研究结果与先前发表的研究结果相结合，几乎没有证据表明AR的常见遗传变异与子宫内膜癌风险之间存在一致的关联。
