We tested the hypothesis that the risk of colorectal cancer (CRC), advanced colorectal neoplasia (ACN), and colorectal adenoma among screening participants with different first-degree relatives ...(FDRs) affected by CRC was similar.
A multi-center, prospective colonoscopy study involving 16 Asia-Pacific regions was performed from 2008 to 2015. Consecutive self-referred CRC screening participants aged 40-70 years were recruited, and each subject received one direct optical colonoscopy. The prevalence of CRC, ACN, and colorectal adenoma was compared among subjects with different FDRs affected using Pearson's χ
tests. Binary logistic regression analyses were performed to evaluate the risk of these lesions, controlling for recognized risk factors including age, gender, smoking habits, alcohol drinking, body mass index, and the presence of diabetes mellitus.
Among 11,797 asymptomatic subjects, the prevalence of CRC was 0.6% (none: 0.6%; siblings: 1.1%; mother: 0.5%; father: 1.2%; ≥2 members: 3.1%, P<0.001), that of ACN was 6.5% (none: 6.1%; siblings: 8.3%; mother: 7.7%; father: 8.7%; ≥2 members: 9.3%, P<0.001), and that of colorectal adenoma was 29.3% (none: 28.6%; siblings: 33.5%; mother: 31.8%; father: 31.1%; ≥2 members: 38.1%, P<0.001). In multivariate regression analyses, subjects with at least one FDR affected were significantly more likely to have CRC (adjusted odds ratio (AOR)=2.02-7.89), ACN (AOR=1.55-2.06), and colorectal adenoma (AOR=1.31-1.92) than those without a family history. The risk of CRC (AOR=0.90, 95% confidence interval (CI) 0.34-2.35, P=0.830), ACN (AOR=1.07, 95% CI 0.75-1.52, P=0.714), and colorectal adenoma (AOR=0.96, 95% CI 0.78-1.19, P=0.718) in subjects with either parent affected was similar to that of subjects with their siblings affected.
The risk of colorectal neoplasia was similar among subjects with different FDRs affected. These findings do not support the need to discriminate proband identity in screening participants with affected FDRs when their risks of colorectal neoplasia were estimated.
Somatic genome rearrangements are thought to play important roles in cancer development. We optimized a long-span paired-end-tag (PET) sequencing approach using 10-Kb genomic DNA inserts to study ...human genome structural variations (SVs). The use of a 10-Kb insert size allows the identification of breakpoints within repetitive or homology-containing regions of a few kilobases in size and results in a higher physical coverage compared with small insert libraries with the same sequencing effort. We have applied this approach to comprehensively characterize the SVs of 15 cancer and two noncancer genomes and used a filtering approach to strongly enrich for somatic SVs in the cancer genomes. Our analyses revealed that most inversions, deletions, and insertions are germ-line SVs, whereas tandem duplications, unpaired inversions, interchromosomal translocations, and complex rearrangements are over-represented among somatic rearrangements in cancer genomes. We demonstrate that the quantitative and connective nature of DNA-PET data is precise in delineating the genealogy of complex rearrangement events, we observe signatures that are compatible with breakage-fusion-bridge cycles, and we discover that large duplications are among the initial rearrangements that trigger genome instability for extensive amplification in epithelial cancers.
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