Gibbs M, Stanford J L, McIndoe R A, Jarvik G P, Kolb S, Goode E L, Chakrabarti L, Schuster E F, Buckley V A, Miller E L, Brandzel S, Li S, Hood L, Ostrander E A
Division of Clinical Research, Fred Hutchinson Cancer Research Center, D2-190, Seattle, WA 98109-1024, USA.
Am J Hum Genet. 1999 Mar;64(3):776-87. doi: 10.1086/302287.
Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.
我们将来自70个前列腺癌（PC）高风险家族的基因组筛查数据，与这些家族以及另外71个家族的候选区域定位数据相结合，已将一个潜在的遗传性PC易感基因座定位到1号染色体的1p36区域。因为在一些PC高风险家族的研究中观察到原发性脑癌（BC）病例过多，并且因为在BC中经常观察到1p36处的杂合性缺失，所以我们进一步评估了12个既有PC病史又有原发性BC血亲的家族。在重组率（θ）为0.06时，这12个家族中与标记D1S507的总体对数优势（LOD）得分为3.22。基于一个先验假设，该组按PC诊断时的年龄进行分层。在较年轻的年龄组（诊断时的平均年龄<66岁）中，观察到与标记D1S407在θ = 0时的最大两点LOD得分为3.65。在没有BC病史的早发和晚发家族中，这种连锁关系均被排除（在θ = 0时，LOD得分分别为-7.12和-6.03）。在排除了12个家族中3个与先前描述的PC易感基因座有更好连锁证据的家族后，与标记D1S407在θ = 0时的两点LOD得分为4.74，提示与1p36区域存在连锁关系。我们得出结论，这些既有PC高风险又有BC家族成员的家族中，很大一部分显示出与1p36区域的连锁关系。
