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Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk.

ABSTRACT: Several different genetic variants at chromosome 8q24 have been related to prostate, breast and colorectal cancer risk with evidence of region-specific risk differentials for various tumor types. We investigated the association between 15 polymorphisms located in 8q24 regions associated with cancer risk in a pooled analysis of 2587 colorectal adenoma cases, 547 colorectal cancer cases and 2798 controls of European descent from four studies. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations. Three polymorphisms (rs10808555, rs6983267 and rs7837328) located between 128.47 and 128.54 Mb were found to be associated with colorectal tumor risk. The association was strongest for the previously reported rs6983267 variant and was similar for both adenoma (OR(per allele) = 1.16, 95% CI: 1.07-1.25, P = 0.0002) and cancer (OR (per allele) = 1.17, 95% CI: 1.01-1.35, P = 0.03). The strength of the association of the regional haplotype containing variant alleles at rs10808555, rs6983267 and rs7837328 but not rs10505476 was greater than that of any single variant of both adenoma (OR = 1.27, P = 0.0001) and cancer (OR = 1.26, P = 0.03). The risk associated with rs6983267 was stronger for multiple adenomas (OR(per allele) = 1.29, P = 5.6 x 10(-6)) than for single adenoma (OR(per allele) = 1.10, P = 0.03) with P(heterogeneity) = 0.008. This study confirms the association between colorectal neoplasia and the 8q24 polymorphisms located between 128.47 and 128.54 Mb and suggests a role for these variants in the formation of multiple adenomas.

SUBMITTER: Berndt SI

PROVIDER: S-EPMC2561994 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMetachronous colorectal cancer refers to patients developing a second colorectal neoplasia diagnosed at least 6 months after the initial cancer diagnosis, excluding recurrence. The aim of this systematic review is to assess the incidence of metachronous colorectal cancer in early-onset colorectal cancer (defined as age at diagnosis of less than 50 years) and to identify risk factors.MethodsThis is a systematic review and meta-analysis performed following the PRISMA statement and registered on PROSPERO. The literature search was conducted in PubMed and Embase. Only studies involving patients with early-onset colorectal cancer (less than 50 years old) providing data on metachronous colorectal cancer were included in the analysis. The primary endpoint was the risk of metachronous colorectal cancer in patients with early-onset colorectal cancer. Secondary endpoints were association with Lynch syndrome, family history and microsatellite instability.ResultsSixteen studies met the inclusion criteria. The incidence of metachronous colorectal cancer was 2.6% (95% c.i. 2.287-3.007). The risk of developing metachronous colorectal cancer in early-onset colorectal cancer versus non-early-onset colorectal cancer patients demonstrated an OR of 0.93 (95% c.i. 0.760-1.141). The incidence of metachronous colorectal cancer in patients with Lynch syndrome was 18.43% (95% c.i. 15.396-21.780), and in patients with family history 10.52% (95% c.i. 5.555-17.659). The proportion of metachronous colorectal cancer tumours in the microsatellite instability population was 19.7% (95% c.i. 13.583-27.2422).ConclusionThe risk of metachronous colorectal cancer in patients with early-onset colorectal cancer is comparable to those with advanced age, but it is higher in patients with Lynch syndrome, family history and microsatellite instability. This meta-analysis demonstrates the need to personalize the management of patients with early-onset colorectal cancer according to their risk factors.

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Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk.

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