Earl Julie, Yan Li, Vitone Louis J, Risk Janet, Kemp Steve J, McFaul Chris, Neoptolemos John P, Greenhalf William, Kress Ralf, Sina-Frey Mercedes, Hahn Stephan A, Rieder Harald, Bartsch Detlef K
Division of Surgery and Oncology, University of Liverpool, Liverpool, United Kingdom.
Cancer Epidemiol Biomarkers Prev. 2006 Oct;15(10):1948-55. doi: 10.1158/1055-9965.EPI-06-0376.
Familial pancreatic cancer (FPC) describes a group of families where the inheritance of pancreatic cancer is consistent with an autosomal-dominant mode of inheritance. The 4q32-34 region has been previously identified as a potential locus for FPC in a large American family.
The region was allelotyped in 231 individuals from 77 European families using nine microsatellite markers, and haplotyping was possible in 191 individuals from 41 families. Families were selected based on at least two affected first-degree relatives with no other cancer syndromes.
Linkage to most of the locus was excluded based on LOD scores less than -2.0. Eight families were excluded from linkage to 4q32-34 based on haplotypes not segregating with the disease compared with a predicted six to seven families. Two groups of families were identified, which seem to share common alleles within the minimal disease-associated region of 4q32-34, one group with an apparently earlier age of cancer death than the other pancreatic cancer families. Four genes were identified with potential tumor suppressor roles within the locus in regions that could not be excluded based on the LOD score. These were HMGB2, PPID, MORF4, and SPOCK3. DNA sequence analysis of exons of these genes in affected individuals and in pancreatic cancer cell lines did not reveal any mutations.
This locus is unlikely to harbor a FPC gene in the majority of our European families.
家族性胰腺癌（FPC）指的是一组家族，其中胰腺癌的遗传符合常染色体显性遗传模式。先前在一个美大家族中，4q32 - 34区域已被确定为FPC的一个潜在位点。
使用9个微卫星标记对来自77个欧洲家族的231名个体进行该区域的等位基因分型，对来自41个家族的191名个体进行单倍型分型。这些家族是基于至少两名受影响的一级亲属且无其他癌症综合征而选择的。
基于小于 -2.0的对数优势分数（LOD），排除了与该位点大部分区域的连锁关系。与预测的6至7个家族相比，基于单倍型不与疾病分离，8个家族被排除与4q32 - 34的连锁关系。确定了两组家族，它们似乎在4q32 - 34最小疾病相关区域内共享共同等位基因，一组癌症死亡年龄明显早于其他胰腺癌家族。在基于LOD分数无法排除的区域内，该位点确定了4个具有潜在肿瘤抑制作用的基因。它们是HMGB2、PPID、MORF4和SPOCK3。对受影响个体和胰腺癌细胞系中这些基因的外显子进行DNA序列分析未发现任何突变。
在我们大多数欧洲家族中，该位点不太可能含有FPC基因。
