Title | Identification of susceptibility genes for cancer in a genome-wide scan: results from the colon neoplasia sibling study. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Daley, D, Lewis, S, Platzer, P, MacMillen, M, Willis, J, Elston, RC, Markowitz, SD, Wiesner, GL |
Journal | Am J Hum Genet |
Volume | 82 |
Issue | 3 |
Pagination | 723-36 |
Date Published | 2008 Mar |
ISSN | 1537-6605 |
Keywords | Adult, Aged, Breast Neoplasms, Chromosomes, Human, Pair 1, Colonic Neoplasms, Female, Genes, Neoplasm, Genetic Linkage, Genetic Predisposition to Disease, Genetic Testing, Genome, Human, Humans, Male, Middle Aged, Siblings |
Abstract | Colorectal cancer (CRC) is the third most commonly diagnosed cancer in Americans and is the second leading cause of cancer mortality. Only a minority ( approximately 5%) of familial CRC can be explained by known genetic variants. To identify susceptibility genes for familial colorectal neoplasia, the colon neoplasia sibling study conducted a comprehensive, genome-wide linkage scan of 194 kindreds. Clinical information (histopathology, size and number of polyps, and other primary cancers) was used in conjunction with age at onset and family history for classification of the families into five phenotypic subgroups (severe histopathology, oligopolyposis, young, colon/breast, and multiple cancer) prior to analysis. By expanding the traditional affected-sib-pair design to include unaffected and discordant sib pairs, analytical power and robustness to type I error were increased. Sib-pair linkage statistics and Haseman-Elston regression identified 19 linkage peaks, with interesting results for chromosomes 1p31.1, 15q14-q22, 17p13.3, and 21. At marker D1S1665 (1p31.1), there was strong evidence for linkage in the multiple-cancer subgroup (p = 0.00007). For chromosome 15q14-q22, a linkage peak was identified in the full-sample (p = 0.018), oligopolyposis (p = 0.003), and young (p = 0.0009) phenotypes. This region includes the HMPS/CRAC1 locus associated with hereditary mixed polyposis syndrome (HMPS) in families of Ashkenazi descent. We provide compelling evidence linking this region in families of European descent with oligopolyposis and/or young age at onset ( |
DOI | 10.1016/j.ajhg.2008.01.007 |
Alternate Journal | Am. J. Hum. Genet. |
PubMed ID | 18313025 |
PubMed Central ID | PMC2427227 |
Grant List | GM28356 / GM / NIGMS NIH HHS / United States K23 1K23CA81308 / CA / NCI NIH HHS / United States P30CA43703 / CA / NCI NIH HHS / United States P41 RR0365 / RR / NCRR NIH HHS / United States U01 CA82901 / CA / NCI NIH HHS / United States |