Study report - GWAS of Colorectal cancer (HGVST1828)
GWAS Central identifier | HGVST1828 | ||||||||||
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Study name | GWAS of Colorectal cancer | ||||||||||
Total markers imported | 14 | ||||||||||
Phenotype(s) tested | Colorectal cancer |
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Study design | Case-control study | ||||||||||
Genotype platforms |
SNaPshot methodology validated by Sanger sequencing | ||||||||||
Abstract | To determine if the at-risk single-nucleotide polymorphism (SNP) alleles for colorectal cancer (CRC) could contribute to clinical situations suggestive of an increased genetic risk for CRC, we performed a prospective national case-control study based on highly selected patients (CRC in two first-degree relatives, one before 61 years of age; or CRC diagnosed before 51 years of age; or multiple primary CRCs, the first before 61 years of age; exclusion of Lynch syndrome and polyposes) and controls without personal or familial history of CRC. SNPs were genotyped using SNaPshot, and statistical analyses were performed using Pearson's χ(2) test, Cochran-Armitage test of trend and logistic regression. We included 1029 patients and 350 controls. We confirmed the association of CRC risk with four SNPs, with odds ratio (OR) higher than previously reported: rs16892766 on 8q23.3 (OR: 1.88, 95% confidence interval (CI): 1.30-2.72; P=0.0007); rs4779584 on 15q13.3 (OR: 1.42, CI: 1.11-1.83; P=0.0061) and rs4939827 and rs58920878/Novel 1 on 18q21.1 (OR: 1.49, CI: 1.13-1.98; P=0.007 and OR: 1.49, CI: 1.14-1.95; P=0.0035). We found a significant (P<0.0001) cumulative effect of the at-risk alleles or genotypes with OR at 1.62 (CI: 1.10-2.37), 2.09 (CI: 1.43-3.07), 2.87 (CI: 1.76-4.70) and 3.88 (CI: 1.72-8.76) for 1, 2, 3 and at least 4 at-risk alleles, respectively, and OR at 1.71 (CI: 1.18-2.46), 2.29 (CI: 1.55-3.38) and 6.21 (CI: 2.67-14.42) for 1, 2 and 3 at-risk genotypes, respectively. Combination of SNPs may therefore explain a fraction of clinical situations suggestive of an increased risk for CRC. | ||||||||||
Submission information |
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Author communication |
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Links | Not supplied | ||||||||||
Background | An important fraction of clinical situations suggestive of an increased genetic risk for CRC cannot be explained by a simple Mendelian model involving one of these key CRC genes. | ||||||||||
Objectives | To determine if the at risk SNP alleles for colorectal cancer (CRC) could contribute to clinical situations suggestive of an increased genetic risk for CRC. | ||||||||||
Key results | We confirmed the association of CRC risk with 4 SNPs, with odds ratio (OR) higher than previously reported : rs16892766 on 8q23.3 (OR: 1.88, 95% confidence interval (CI): 1.30-2.72; p=0.0007); rs4779584 on 15q13.3 (OR: 1.42, CI: 1.11-1.83; p=0.0061), and rs4939827 and rs58920878/Novel 1 on 18q21.1 (OR: 1.49, CI: 1.13-1.98; p=0.007 and OR: 1.49, CI: 1.14-1.95; p=0.0035). We found a significant (p< 0.0001) cumulative effect of the at risk alleles or genotypes with OR at 1.62 (CI: 1.10-2.37); 2.09 (CI: 1.43-3.07); 2.87 (CI: 1.76-4.70) and 3.88 (CI: 1.72-8.76) for 1, 2, 3 and at least 4 at risk alleles and OR at 1.71 (CI: 1.18-2.46); 2.29 (CI: 1.55-3.38) and 6.21 (CI: 2.67-14.42) for 1, 2 and 3 at risk genotypes. | ||||||||||
Conclusions | This study supports that a fraction of clinical situations suggestive of an increased risk for CRC may be explained by a combination of SNPs involved in the genetic determinism of CRC. | ||||||||||
Reason for study size | Not supplied | ||||||||||
Study power | Not supplied | ||||||||||
Sources of bias | Not supplied | ||||||||||
Limitations | Not supplied | ||||||||||
Acknowledgements | This work was supported by the French National Cancer Institute (INCa-DGOS_1332). | ||||||||||
Related citations |
Baert-Desurmont S, Charbonnier F, Houivet E et al.
Clinical relevance of 8q23, 15q13 and 18q21 SNP genotyping to evaluate colorectal cancer risk. European journal of human genetics : EJHG 2016;24(1):99-105 |