Seemanová E, Hoch J, Herzogová J, Kawaciuk I, Janda J, Kohoutová M, Seeman P, Varon R, Sperling K
Oddelení klinické genetiky Ustavu biologie a lékarské genetiky 2. LF UK, Praha.
Cas Lek Cesk. 2006;145(3):201-3.
Mutations 657del5 and R215W in exon 6 of tumor suppressor gene NBS I are found in 1% Slavic populations. Increased occurrence of cancer was repeatedly reported in adult relatives of patients with Nijmegen breakage syndrome. Among children with oncological problematic, nonsignificantly increased frequency of NBS1 heterozygotes was found, which seems not to play any important role in cancerogenesis in childhood. However, the proportion of NBS heterozygotes among adult patients with malignancies could be significant and their therapy and follow up should respect their hyperradiosensitivity.
Mutations in exon were studied in 706 adult patients with malignancies. We found 5 NBS heterozygotes, which not more than the population prevalence (1:129-165). Increased frequency of NBS heterozygotes was found among patients with colon and rectal cancer (2/101), breast cancer (1/60), skin malignancies (1/98).
Surprisingly only one NBS heterozygote was found among 228 patients with nonHodgkin lymphoma, the malignancy which is a common complication in NBS homozygotes. Other types of malignancies were uncommon and only one R215W heterozygote was found. Comparison frequency of NBS heterozygotes with incidence NBS among person older than 70 years shows significant difference. Prevention of malignancies by avoidance from ionisation could be realized also in relatives of patients after identification of their genotype.
肿瘤抑制基因NBS1外显子6中的657del5和R215W突变在1%的斯拉夫人群中被发现。尼曼-匹克氏病断裂综合征患者的成年亲属中癌症发生率反复被报道有所增加。在患有肿瘤问题的儿童中，发现NBS1杂合子的频率有非显著性增加，这似乎在儿童癌症发生中不发挥任何重要作用。然而，成年恶性肿瘤患者中NBS杂合子的比例可能是显著的，并且他们的治疗和随访应该考虑到他们的高辐射敏感性。
对706例成年恶性肿瘤患者的外显子突变进行了研究。我们发现了5例NBS杂合子，其数量不超过人群患病率（1:129 - 165）。在结肠癌和直肠癌患者（2/101）、乳腺癌患者（1/60）、皮肤恶性肿瘤患者（1/98）中发现NBS杂合子的频率增加。
令人惊讶的是，在228例非霍奇金淋巴瘤患者中仅发现1例NBS杂合子，非霍奇金淋巴瘤是NBS纯合子的常见并发症。其他类型的恶性肿瘤并不常见，仅发现1例R215W杂合子。将70岁以上人群中NBS杂合子的频率与NBS发病率进行比较显示出显著差异。在确定患者亲属的基因型后，通过避免电离来预防恶性肿瘤也是可行的。
