Genetic polymorphisms of p21 are associated with risk of squamous cell carcinoma of the head and neck
Genetic polymorphisms of p21 are associated with risk of squamous cell carcinoma of the head and neck
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DOI：
10.1093/carcin/bgi105
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发表时间：
2005-09-01
期刊：
影响因子：
4.7
通讯作者：
Wei, QY
中科院分区：
文献类型：
--
作者：
Li, GJ;Liu, ZS;Wei, QY
p21 (Waf1/Cip1/CDKN1A) 蛋白调节从 G1 期到 S 期的转变，在调节细胞周期控制、细胞凋亡和细胞生长中具有重要作用。 p21 基因密码子 31 处（p21 C98A，dbSNP rs1801270）和 3' 非翻译区（p21 T70C，dbSNP rs1059234）的两个多态性可能对蛋白质功能产生影响，因此可能在癌症的发展中发挥作用。我们假设这两个 p21 多态性与头颈鳞状细胞癌 (SCCHN) 的风险相关。我们在一项以医院为基础的病例对照研究中检验了这一假设，该研究纳入了 712 名新诊断为 SCCHN 的患者和 1222 名无癌症对照者，这些对照者按年龄、性别和种族进行频率匹配。所有受试者均为非西班牙裔白人。我们的结果表明，变异等位基因和基因型在病例中比对照中更常见（p21C70T 分别为 P < 0.001 和 P = 0.013，p21C98A 分别为 P < 0.001 和 P = 0.035）。与 p21 70CC 基因型相比，变异 p21 70TC [比值比 (OR) = 1.47，95% 置信区间 (CI) = 1.12-1.93] 和组合 p21 70TC/TT (OR = 1.49，95% CI = 1.14-1.95) 基因型相关的 SCCHN 风险显着更高。同样，与 p21 98CC 基因型相比，变异 p21 98AC（OR = 1.32，95% CI = 1.00-1.73）和组合 p21 98AC/AA（OR = 1.37，95% CI = 1.05-1.79）基因型相关的 SCCHN 风险也显着更高。当通过风险等位基因的数量一起评估这两种多态性时，SCCHN 风险显着增加，这取决于风险等位基因的数量（P 趋势 = 0.001）。我们的结果表明，这两个 p21 多态性的存在可能是 SCCHN 遗传易感性的标志。
The p21 (Waf1/Cip1/CDKN1A) protein regulates the transition from the G1 to the S phase and has an important role in modulating cell-cycle control, apoptosis and cell growth. Two polymorphisms of the p21 gene at codon 31 (p21 C98A, dbSNP rs1801270) and at the 3' untranslated region (p21 T70C, dbSNP rs1059234) may have an effect on the protein function and may thus play a role in the development of cancer. We hypothesized that these two p21 polymorphisms are associated with the risk of squamous cell carcinoma of the head and neck (SCCHN). We tested this hypothesis in a hospital-based case-control study of 712 patients newly diagnosed with SCCHN and 1222 cancer-free controls who were frequency-matched by age, sex and ethnicity. All subjects were non-Hispanic whites. Our results showed that the variant alleles and genotypes were more common among cases than among controls (P < 0.001 and P = 0.013 for p21C70T, and P < 0.001 and P = 0.035 for p21C98A, respectively). Compared with the p21 70CC genotype, there was a significantly greater risk of SCCHN associated with the variant p21 70TC [odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.12-1.93] and combined p21 70TC/TT (OR = 1.49, 95% CI = 1.14-1.95) genotypes. Similarly, compared with the p21 98CC genotype, there was also a significantly greater SCCHN risk associated with the variant p21 98AC (OR = 1.32, 95% CI = 1.00-1.73) and combined p21 98AC/AA (OR = 1.37, 95% CI = 1.05-1.79) genotypes. When these two polymorphisms were evaluated together by the number of risk alleles, there was a significant increase in SCCHN risk that was dependent on the number of risk alleles (P-trend = 0.001). Our results suggest that the presence of these two p21 polymorphisms may be a marker of genetic susceptibility to SCCHN.