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Colorectal cancer susceptibility loci in a population-based study : associations with morphological parameters
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- Ghazi, Sam (author)
- Karolinska Institutet
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- von Holst, Susanna (author)
- Karolinska Institutet
- Picelli, Simone (author)
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- Tenesa, Albert (author)
- Farrington, Susan M (author)
- Campbell, Harry (author)
- Dunlop, Malcolm G (author)
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- (creator_code:org_t)
- Elsevier BV, 2010
- 2010
- English.
- In: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 177:6, s. 2688-2693
- Journal article (peer-reviewed)
Abstract
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- Recent genome-wide association studies have identified multiple genetic loci and single nucleotide polymorphisms (SNPs) associated with either increased or decreased risk of colorectal cancer (CRC). In the present study, our objective was to determine whether 11 of the new susceptibility CRC loci are associated with tumor morphology and to confirm these loci as distinct and etiologically different risk factors in the development of CRC. The following clinical and morphological parameters were analyzed in 1572 samples: tumor size, T-stage, lymph node metastases, degree of differentiation, mucin production, Crohn-like peritumoral lymphocytic infiltration, tumor-infiltrating lymphocytes, desmoplastic reaction, necrosis, invasion of blood or lymph vessels, perineural growth, medullary type, budding, and tumor margin. One SNP from each of the 11 loci (rs6983267 on 8q24.21, rs16892766 on 8q23.3, rs719725 on 9p24.1, rs10795668 on 10p14, rs3802842 on 11q23.1, rs4444235 on 14q22.2, rs4779584 on 15q13.3, rs9929218 on 16q22.1, rs4939827 on 18q21.1, rs10411210 on 19q13.11, and rs961253 on 20p12.3) was genotyped for all cases. Odds ratios, 95% confidence intervals, and the corresponding P values were calculated for the 11 SNPs identified above. A cross tabulation between SNPs and morphology was performed. Several loci showed statistically significant associations with specific phenotypes. The findings are consistent with pathogenic variants in several loci that act in distinct CRC and morphogenetic pathways. Further large-scale studies are required to validate these findings.
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