Santarosa Manuela, Bidoli Ettore, Gallo Angelo, Steffan Agostino, Boiocchi Mauro, Viel Alessandra
Division of Experimental Oncology 1, Centro di Riferimento Oncologico-IRCCS, Aviano, Italy.
Oncol Rep. 2002 May-Jun;9(3):639-44.
The CAG repeat (CAGn) present in the N-terminal region of the androgen receptor (AR) inversely correlates with AR transactivation activity. The aim of this study was to investigate whether polymorphic variation in the CAGn length is associated with the risk of developing ovarian cancer. Using a case-control study design 121 women with histologically confirmed ovarian cancer and 100 controls (healthy women) were genotyped for AR-CAG length. No marked difference in the mean length of CAGn was observed between ovarian cancer patients and controls. However, when considering patients with positive personal or family history of tumor (PPFHT), the mean lengths of the long allele, the short allele and the average of the 2 alleles were longer than in the controls. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were computed after allowance for age. We observed an increase in the risk of ovarian cancer, in terms of OR, in women with CAGn >or=22 (OR=2.17, 95% CI:1.10-4.27). The increase of relative risk was particularly high in women with CAGn >or=22 belonging to the PPFHT group: OR=3.52 (95% CI 1.18-10.47). We also found a statistically significant trend (chi2 trend=4.91; p=0.03) towards an increased risk of ovarian cancer with increasing CAGn length (from <or=21 to 22-23, 24-25 and >or=26). Again, a strong association between increase in CAGn and risk of ovarian cancer was observed in PPFHT patients (chi2 trend=6.38; p=0.01). The results suggest that AR-CAG repeat length could play a role as modifier of the ovarian cancer risk conferred by highly penetrant genes rather than itself conferring a low risk.
雄激素受体（AR）N端区域存在的CAG重复序列（CAGn）与AR反式激活活性呈负相关。本研究旨在调查CAGn长度的多态性变异是否与卵巢癌发生风险相关。采用病例对照研究设计，对121例经组织学确诊的卵巢癌女性和100例对照（健康女性）进行AR - CAG长度基因分型。卵巢癌患者与对照之间未观察到CAGn平均长度有明显差异。然而，当考虑有肿瘤个人或家族史阳性（PPFHT）的患者时，长等位基因、短等位基因的平均长度以及两个等位基因的平均值均长于对照。在考虑年龄因素后计算优势比（OR）及其相应的95%置信区间（CI）。我们观察到CAGn≥22的女性患卵巢癌的风险增加（OR = 2.17，95% CI：1.10 - 4.27）。在属于PPFHT组且CAGn≥22的女性中，相对风险增加尤为显著：OR = 3.52（95% CI 1.18 - 10.47）。我们还发现随着CAGn长度增加（从≤21到22 - 23、24 - 25和≥26），卵巢癌风险增加存在统计学显著趋势（χ²趋势 = 4.91；p = 0.03）。同样，在PPFHT患者中观察到CAGn增加与卵巢癌风险之间存在强关联（χ²趋势 = 6.38；p = 0.01）。结果表明，AR - CAG重复长度可能作为高 penetrant基因赋予的卵巢癌风险的修饰因子发挥作用，而非自身赋予低风险。
