Lewis C M, Neuhausen S L, Daley D, Black F J, Swensen J, Burt R W, Cannon-Albright L A, Skolnick M H
Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City, 84108, USA.
Cancer Res. 1996 Mar 15;56(6):1382-8.
Colorectal cancer (CRC) has a strong familial component. Candidate genes for colorectal cancer have been identified through mutations in four mismatch repair genes (hMSH2, hMLH1, hPMS1, and hPMS2) and genes that are deleted or mutated in tumors (DCC, APC, and p53). Linkage analysis of candidate loci/regions was performed in 10 kindreds ascertained for common colorectal cancer from the Utah Population Database. Evidence for linkage to candidate genes was assessed using two- or three-point logarithm of the odds ratio scores with markers spanning the region of localization. One kindred is linked to hMSH2 and also fits the criteria for hereditary nonpolyposis colorectal cancer, having early age of onset and high penetrance for CRC. The remaining nine kindreds are unlinked to the candidate genes tested. These kindreds have a later age of onset and a lower penetrance than hereditary nonpolyposis colorectal cancer kindreds. these results indicate that further unmapped susceptibility loci may be responsible for much of the familial aggregation of CRC.
结直肠癌（CRC）具有很强的家族性因素。通过四个错配修复基因（hMSH2、hMLH1、hPMS1和hPMS2）的突变以及在肿瘤中缺失或突变的基因（DCC、APC和p53），已确定了结直肠癌的候选基因。对从犹他州人口数据库中确定的10个患常见结直肠癌的家族进行了候选基因座/区域的连锁分析。使用跨越定位区域的标记，通过两点或三点优势比分数的对数来评估与候选基因连锁的证据。一个家族与hMSH2连锁，并且符合遗传性非息肉病性结直肠癌的标准，发病年龄早且患结直肠癌的外显率高。其余九个家族与所检测的候选基因不连锁。这些家族的发病年龄比遗传性非息肉病性结直肠癌家族晚，外显率也较低。这些结果表明，尚未定位的其他易感基因座可能是导致结直肠癌家族聚集的主要原因。
