Background Colorectal cancer is the fourth most common type of cancer and the second most common cause of cancer death. Fewer than 5% of colon cancers arise in the presence of a clear hereditary cancer condition; however, current estimates suggest that an additional 15–25% of colorectal cancers arise on the basis of unknown inherited factors.
Aim To identify additional genetic factors responsible for colon cancer.
Methods A large kindred with excess colorectal cancer was identified through the Utah Population Database and evaluated clinically and genetically for inherited susceptibility.
Results A major genetic locus segregating with colonic polyps and cancer in this kindred was identified on chromosome 13q with a non-parametric linkage score of 24 (LOD score of 2.99 and p=0.001). The genetic region spans 21 Mbp and contains 27 RefSeq genes. Sequencing of all candidate genes in this region failed to identify a clearly deleterious mutation; however, polymorphisms segregating with the phenotype were identified. Chromosome 13q is commonly gained and overexpressed in colon cancers and correlates with metastasis, suggesting the presence of an important cancer progression gene. Evaluation of tumours from the kindred revealed a gain of 13q as well.
Conclusions This identified region may contain a novel gene responsible for colon cancer progression in a significant proportion of sporadic cancers. Identification of the precise gene and causative genetic change in the kindred will be an important next step to understanding cancer progression and metastasis.
- Colon cancer
- genetic linkage
- chromosome 13q
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Funding This study was supported by National Cancer Institute grants R01-CA40641 and PO1-CA73992; additional support was provided by a Cancer Center Support Grant P30-CA42014, General Clinical Research Center Grant M01-RR00064 and N01-PC-67000, Utah Cancer Registry grant N01-PC-35141 from the National Cancer Institute's SEER program with additional support from the Utah State Department of Health and the University of Utah, and by the Huntsman Cancer Foundation. Database support to the Utah Population Database is provided by the Huntsman Cancer Foundation. Other Funders: NIH; Huntsman Cancer Foundation, Utah State Department of Health.
Competing interests None.
Ethics approval This study was conducted with the approval of the University of Utah Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.
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