Buyru Nur, Altinisik Julide, Demokan Semra, Dalay Nejat
Department of Medical Biology, Cerrahpasa Medical School, Istanbul University, Istanbul, Turkey.
Cancer Detect Prev. 2007;31(3):207-13. doi: 10.1016/j.cdp.2007.04.004. Epub 2007 Jun 18.
The biological significance of sequence variants in form of SNPs needs to be carefully evaluated, as conflicting associations with cancer predisposition have been reported. Haplotypes, the combination of closely linked alleles on a chromosome, play key roles in the study of the genetic basis of disease. There is strong evidence that different polymorphisms within a single gene in cis position can interact to create a large effect on the observed phenotype. Several polymorphisms have been reported in the p53 gene. Some of these are within the coding region and may affect the function of the p53 protein, others are within introns or non-coding regions, and their significance is unclear. In this study, we investigated the association of specific p53 genotypes and haplotypes with risk of breast cancer.
One hundred and fifteen patients with breast cancer and 63 healthy individuals were analyzed. DNA was isolated by salting out. The polymorphic sites were analyzed by PCR RFLP. Pearson's chi(2) and Kolmogorof Simirnow tests were used for statistical analyses. Extended haplotype frequencies were estimated.
The distribution of the genotypes was similar for all three polymorphisms in the cases and the controls. Our estimated haplotype results indicate that the intron 3 (+16bp)|exon 4 (Arg) diplotype and the intron 3 (+16bp)|exon 4 (Arg)|intron 6 (G) haplotype combinations are overrepresented in the breast cancer group, suggesting that the intron 3 (+16bp)|exon 4 (Arg) alleles may play a role in breast carcinogenesis.
We conclude that two haplotypes harboring the intron 3 polymorphic (+16bp) allele are associated with a higher risk of breast cancer in the Turkish population.
单核苷酸多态性（SNP）形式的序列变异的生物学意义需要仔细评估，因为已有关于癌症易感性的相互矛盾的关联报道。单倍型是染色体上紧密连锁的等位基因的组合，在疾病遗传基础的研究中起着关键作用。有强有力的证据表明，顺式位置上单个基因内的不同多态性可以相互作用，对观察到的表型产生重大影响。p53基因中已报道了几种多态性。其中一些位于编码区内，可能影响p53蛋白的功能，其他的位于内含子或非编码区内，其意义尚不清楚。在本研究中，我们调查了特定p53基因型和单倍型与乳腺癌风险的关联。
分析了115例乳腺癌患者和63名健康个体。通过盐析法分离DNA。通过PCR-RFLP分析多态性位点。采用Pearson卡方检验和Kolmogorof-Simirnow检验进行统计分析。估计扩展单倍型频率。
病例组和对照组中所有三种多态性的基因型分布相似。我们估计的单倍型结果表明，内含子3（+16bp）|外显子4（Arg）双倍型和内含子3（+16bp）|外显子4（Arg）|内含子6（G）单倍型组合在乳腺癌组中过度出现，提示内含子3（+16bp）|外显子4（Arg）等位基因可能在乳腺癌发生中起作用。
我们得出结论，携带内含子3多态性（+16bp）等位基因的两种单倍型与土耳其人群中较高的乳腺癌风险相关。
