Klinkov A A, Nikitin E A, Maiorova O V, Ivanov M A, Strelnikov V V, Babenko O V, Zemlyakova V V, Kuznetsova E B, Zaletayev D V
Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478, Moskvorechie St.1, Moscow, Russia.
Ann Hum Genet. 2004 Jul;68(Pt 4):362-6. doi: 10.1046/j.1529-8817.2004.00101.x.
TNR/11q#1 is a polymorphic trinucleotide (GCC)n repeat located within the minimal region of the 11q deletion in chronic lymphocytic leukemia (CLL). It was recently shown that certain alleles of this repeat are associated with a worse prognosis in CLL patients. To investigate the role of TNR/11q#1 variants as risk-modifying factors in leukemogenesis, we conducted a case-control study on 113 acute lymphotic leukemia (ALL) patients, 82 CLL patients and 146 healthy controls of Russian origin. Comparison of allele and genotype distributions in the control, ALL and CLL groups, performed by Fisher's exact test with two-sized P-value, showed significant decrease in the presence of the GCC(6) allele in the ALL and CLL groups compared to controls. Moreover, 'rare' alleles GCC(7-8) and GCC(13-14) were significantly overrepresented in the ALL group versus controls. We found that CLL risk genotypes were those with both alleles containing more than 6 GCC repeats (P = 0,0212, odds ratio = 1,68 (95% CI, 1,121...2,531)). ALL risk genotypes include three allele combination variants: 1) both alleles containing more than 6 GCC repeats (P = 0,0019, odds ratio = 1,756 (95% CI 1,223...2,502)); 2) one of the alleles containing 7 or 8 repeats (P = 0,0155, odds ratio = 18,22 (95% CI 1,93...136.37)); 3) one of the alleles containing more than 12 repeats (P = 0,0209, Odds ratio = 2,599 (95% CI 1,161...5,815)). Association of certain alleles and genotypes of the TNR/11q#1 repeat with both acute and chronic lymphocytic leukemia suggests the presence of a cancer related gene, involved in a wide spectrum of neoplasia, in the vicinity of this repeat.
TNR/11q#1是一种多态性三核苷酸(GCC)n重复序列，位于慢性淋巴细胞白血病(CLL) 11q缺失的最小区域内。最近研究表明，该重复序列的某些等位基因与CLL患者较差的预后相关。为了研究TNR/11q#1变体在白血病发生过程中作为风险调节因子的作用，我们对113例急性淋巴细胞白血病(ALL)患者、82例CLL患者和146名俄罗斯裔健康对照者进行了病例对照研究。通过双尾P值的Fisher精确检验对对照组、ALL组和CLL组的等位基因和基因型分布进行比较，结果显示ALL组和CLL组中GCC(6)等位基因的出现频率与对照组相比显著降低。此外，与对照组相比，ALL组中“罕见”等位基因GCC(7 - 8)和GCC(13 - 14)的比例显著过高。我们发现CLL风险基因型是那些两个等位基因均包含超过6个GCC重复序列的基因型(P = 0.0212，优势比 = 1.68 (95%可信区间，1.121...2.531))。ALL风险基因型包括三种等位基因组合变体：1) 两个等位基因均包含超过6个GCC重复序列(P = 0.0019，优势比 = 1.756 (95%可信区间1.223...2.502))；2) 其中一个等位基因包含7个或8个重复序列(P = 0.0155，优势比 = 18.22 (95%可信区间1.93...136.37))；3) 其中一个等位基因包含超过12个重复序列(P = 0.0209，优势比 = 2.599 (95%可信区间1.161...5.815))。TNR/11q#1重复序列的某些等位基因和基因型与急性和慢性淋巴细胞白血病均相关，这表明在该重复序列附近存在一个与癌症相关的基因，它参与了广泛的肿瘤形成过程。
