Institute of Medical Science, Laboratory of Molecular Medicine, Human Genome Center, The University of Tokyo, Tokyo, Japan.
J Hum Genet. 2012 Apr;57(4):235-7. doi: 10.1038/jhg.2012.9. Epub 2012 Feb 9.
Gallbladder cancer (GC) is a relatively uncommon cancer with higher incidence in certain areas including Japan. Because of the difficulty in diagnosis, prognosis of GC is very poor. To identify genetic determinants of GC, we conducted a genome-wide association study (GWAS) in 41 GC patients and 866 controls. Association between each single-nucleotide polymorphism (SNP) with GC susceptibility was evaluated by multivariate logistic regression analysis conditioned on age and gender of subjects. SNPs that showed suggestive association (P<1 × 10(-4)) with GC were further examined in 30 cases and 898 controls. SNP rs7504990 in the DCC (deleted in colorectal cancer, 18q21.3) that encodes a netrin 1 receptor achieved a combined P-value of 7.46 × 10(-8) (OR=6.95; 95% CI=3.43-14.08). Subsequent imputation analysis identified multiple SNPs with similarly strong associations in an adjacent genomic region, where loss of heterozygosity was reported in GC and other cancers. Reduced expression of DCC was indicated to be associated with the poorly differentiated histological type, increased proliferation and metastasis through loss of adhesiveness. However, due to the limited sample size investigated here, further replication study and functional analysis would be necessary to further confirm the result of the association.
胆囊癌（GC）是一种相对罕见的癌症，在某些地区（包括日本）发病率较高。由于诊断困难，GC 的预后非常差。为了确定 GC 的遗传决定因素，我们对 41 名 GC 患者和 866 名对照进行了全基因组关联研究（GWAS）。通过多元逻辑回归分析，在考虑了研究对象的年龄和性别后，评估了每个单核苷酸多态性（SNP）与 GC 易感性之间的关联。在 30 例病例和 898 例对照中进一步检查了与 GC 具有提示性关联（P<1 × 10(-4))的 SNP。在 DCC（结直肠癌缺失，18q21.3）中发现的 SNP rs7504990 编码了一种神经纤毛蛋白 1 受体，其合并 P 值为 7.46 × 10(-8)（OR=6.95；95% CI=3.43-14.08）。随后的导入分析确定了在相邻基因组区域中具有类似强关联的多个 SNP，在 GC 和其他癌症中已经报道了这些 SNP 的杂合性丢失。DCC 表达的减少与组织学分化不良、通过丧失黏附性导致的增殖和转移增加有关。然而，由于本研究调查的样本量有限，需要进一步的复制研究和功能分析来进一步证实关联的结果。
