CDKN2A variants in a population-based sample of queensland families with melanoma
CDKN2A variants in a population-based sample of queensland families with melanoma
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DOI：
10.1093/jnci/91.5.446
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发表时间：
1999-03-03
影响因子：
10.3
通讯作者：
Hayward, N
中科院分区：
文献类型：
--
作者：
Aitken, J;Welch, J;Hayward, N
背景：CDKN2A基因突变导致皮肤恶性黑色素瘤（CMM）易感性；然而，这类突变的人群发病率尚不清楚，CDKN2A的多态性也被描述过，但尚不清楚它们是否影响黑色素瘤的风险。我们研究了CDKN2A突变和多态性nifh黑色素瘤风险之间的关系，这些基于人群的家庭样本是通过黑色素瘤先证确定的。方法：我们样本中的482个澳大利亚昆士兰州的家庭先前被定性为具有高、中、低CMM家族风险。从澳大利亚双胞胎登记处抽取的非亲属个体（n = 200个家庭/个人）作为对照受试者。对于高危人群，采用聚合酶链反应、琼脂糖凝胶电泳、等位基因特异性寡核苷酸（ASO）杂交、单链构象多态性分析等方法对CDKN2A基因编码区进行突变筛选，对中、低危家族和对照组进行ASO杂交分析，共发现6个重复突变以及核苷酸（Nts） 442、500、540位点的多态性。CDKN2A突变仅在高危家族中发现（87个家族中有9个[10.3%]），Nt500G（鸟苷）多态性的患病率随着家族风险的增加而线性增加（双侧P = 0.02），并且在CDKN2A突变的9个（主要是凯尔特人）家族中最高。调整人种来源后，风险组与Nt500G等位基因频率的关系减弱（P = 0.25）；而在对照组中，nt500多态性频率与人种血统没有关系。结论：CDKN2A突变在该人群中很少见（约占昆士兰州所有黑色素瘤病例的0.2%），并且似乎仅在最受影响的家族中与黑色素瘤有关。Nt500G等位基因似乎与家族风险有关，但这种关联可能反映了凯尔特血统。
Background: Mutations in the CDKN2A gene confer susceptibility to cutaneous malignant melanoma (CMM); however, the population incidence of such mutations is unknown, Polymorphisms in CDKN2A have also been described, but it is not known whether they influence melanoma risk, We investigated the association of CDKN2A mutations and polymorphisms nifh melanoma risk in a population-based sample of families ascertained through probands with melanoma, Methods: The 482 Queensland, Australia, families in our sample were characterized previously as having high, intermediate, or low family risk of CMM. Unrelated individuals (n = 200 families/individuals) drawn from the Australian Twin Registry served as control subjects. For individuals in the high-risk group, the entire CDKN2A gene coding region was screened for mutations by use of the polymerase chain reaction, agarose gel electrophoresis, allele-specific oligonucleotide (ASO) hybridization, and single-strand conformation polymorphism analysis, The intermediate- and low-risk families and control subjects were analyzed by ASO hybridization for a total of six recurring mutations as well as for polymorphisms at nucleotides (Nts) 442, 500, and 540, Results: CDKN2A mutations were found only in the high-risk families (nine [10.3%] of 87), The prevalence of the Nt500G (guanosine) polymorphism increased linearly with increasing familial risk (two-sided P = .02) and was highest in the nine (primarily Celtic) families with CDKN2A mutations. After adjustment for ethnic origin, the relationship between risk group and the frequency of the Nt500G allele was weakened (P = .25); however, there was no relationship between ethnic origin and Nt500-polymorphism frequency among the control subjects. Conclusions: CDKN2A mutations are rare in this population (approximately 0.2% of all melanoma cases in Queensland) and appear to be associated with melanoma in only the most affected families, The Nt500G allele appears to be associated with familial risk, but this association probably reflects Celtic ancestry.