Rapley E A, Crockford G P, Teare D, Biggs P, Seal S, Barfoot R, Edwards S, Hamoudi R, Heimdal K, Fossâ S D, Tucker K, Donald J, Collins F, Friedlander M, Hogg D, Goss P, Heidenreich A, Ormiston W, Daly P A, Forman D, Oliver T D, Leahy M, Huddart R, Cooper C S, Bodmer J G, Easton D F, Stratton M R, Bishop D T
Sections of Cancer Genetics and Molecular Carcinogenesis, Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK.
Nat Genet. 2000 Feb;24(2):197-200. doi: 10.1038/72877.
Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations. The incidence of TGCT has risen dramatically over the last century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, previously diagnosed TGCT (ref. 7) and a family history of the disease. Brothers of men with TGCT have an 8-10-fold risk of developing TGCT (refs 8,9), whereas the relative risk to fathers and sons is fourfold (ref. 9). This familial relative risk is much higher than that for most other types of cancer. We have collected samples from 134 families with two or more cases of TGCT, 87 of which are affected sibpairs. A genome-wide linkage search yielded a heterogeneity lod (hlod) score of 2.01 on chromosome Xq27 using all families compatible with X inheritance. We obtained a hlod score of 4.7 from families with at least one bilateral case, corresponding to a genome-wide significance level of P=0.034. The proportion of families with UDT linked to this locus was 73% compared with 26% of families without UDT (P=0.03). Our results provide evidence for a TGCT susceptibility gene on chromosome Xq27 that may also predispose to UDT.
睾丸生殖细胞肿瘤（TGCT）影响着每500名男性中的1人，是西欧人群中15至40岁男性最常见的癌症。在过去的一个世纪里，TGCT的发病率急剧上升。已知的TGCT风险因素包括隐睾病史（UDT）、睾丸发育不全、不育、先前诊断出的TGCT（参考文献7）以及该病的家族病史。患有TGCT的男性的兄弟患TGCT的风险是常人的8至10倍（参考文献8、9），而父子之间的相对风险为4倍（参考文献9）。这种家族相对风险远高于大多数其他类型的癌症。我们从134个有两例或更多TGCT病例的家庭中收集了样本，其中87个是患病同胞对。使用所有符合X染色体遗传的家庭进行全基因组连锁搜索，在Xq27染色体上得到了一个异质性对数优势（hlod）分数为2.01。我们从至少有一例双侧病例的家庭中获得了hlod分数为4.7，相当于全基因组显著性水平P = 0.034。与没有UDT的家庭中26%的比例相比，与该基因座相关的有UDT的家庭比例为73%（P = 0.03）。我们的结果为Xq27染色体上的一个TGCT易感基因提供了证据，该基因也可能易导致UDT。
