Dataset Information

Colorectal cancer susceptibility variants and risk of conventional adenomas and serrated polyps: results from three cohort studies.

ABSTRACT:

Background

Increasing evidence suggests that conventional adenomas (CAs) and serrated polyps (SPs) represent two distinct groups of precursor lesions for colorectal cancer (CRC). The influence of common genetic variants on risk of CAs and SPs remain largely unknown.

Methods

Among 27 426 participants within three prospective cohort studies, we created a weighted genetic risk score (GRS) based on 40 CRC-related single nucleotide polymorphisms (SNPs) identified in previous genome-wide association studies; and we examined the association of GRS (per one standard deviation increment) with risk of CAs, SPs and synchronous CAs and SPs, by multivariable logistic regression. We also analysed individual variants in the secondary analysis.

Results

During 18-20?years of follow-up, we documented 2952 CAs, 1585 SPs and 794 synchronous CAs and SPs. Higher GRS was associated with increased risk of CAs [odds ratio (OR)?=?1.17, 95% confidence interval (CI): 1.12-1.21] and SPs (OR?=?1.09, 95% CI: 1.03-1.14), with a stronger association for CAs than SPs (Pheterogeneity=0.01). An even stronger association was found for patients with synchronous CAs and SPs (OR?=?1.32), advanced CAs (OR?=?1.22) and multiple CAs (OR?=?1.25). Different sets of variants were associated with CAs and SPs, with a Spearman correlation coefficient of 0.02 between the ORs associating the 40 SNPs with the two lesions. After correcting for multiple testing, three variants were associated with CAs (rs3802842, rs6983267 and rs7136702) and two with SPs (rs16892766 and rs4779584).

Conclusions

Common genetic variants play a potential role in the conventional and serrated pathways of CRC. Different sets of variants are identified for the two pathways, further supporting the aetiological heterogeneity of CRC.

SUBMITTER: Hang D

PROVIDER: S-EPMC7426026 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Colorectal cancer susceptibility variants and risk of conventional adenomas and serrated polyps: results from three cohort studies.

Hang Dong D Joshi Amit D AD He Xiaosheng X Chan Andrew T AT Jovani Manol M Gala Manish K MK Ogino Shuji S Kraft Peter P Turman Constance C Peters Ulrike U Bien Stephanie A SA Lin Yi Y Hu Zhibin Z Shen Hongbing H Wu Kana K Giovannucci Edward L EL Song Mingyang M

International journal of epidemiology 20200201 1

<h4>Background</h4>Increasing evidence suggests that conventional adenomas (CAs) and serrated polyps (SPs) represent two distinct groups of precursor lesions for colorectal cancer (CRC). The influence of common genetic variants on risk of CAs and SPs remain largely unknown.<h4>Methods</h4>Among 27 426 participants within three prospective cohort studies, we created a weighted genetic risk score (GRS) based on 40 CRC-related single nucleotide polymorphisms (SNPs) identified in previous genome-wid ...[more]

PMID: 31038671

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Project description:Background & aimsEndoscopic screening reduces incidence and mortality of colorectal cancer (CRC) because precursor lesions, such as conventional adenomas or serrated polyps, are removed. Individuals with polypectomies are advised to undergo colonoscopy surveillance to prevent CRC. However, guidelines for surveillance intervals after diagnosis of a precursor lesion, particularly for individuals with serrated polyps, vary widely, and lack sufficient supporting evidence. Consequently, some high-risk patients do not receive enough surveillance and lower-risk subjects receive excessive surveillance.MethodsWe examined the association between findings from first endoscopy and CRC risk among 122,899 participants who underwent flexible sigmoidoscopy or colonoscopy in the Nurses' Health Study 1 (1990-2012), Nurses' Health Study 2 (1989-2013), or the Health Professionals Follow-up Study (1990-2012). Endoscopic findings were categorized as no polyp, conventional adenoma, or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma, with or without cytological dysplasia). Conventional adenomas were classified as advanced (≥10 mm, high-grade dysplasia, or tubulovillous or villous histology) or nonadvanced, and serrated polyps were assigned to categories of large (≥10 mm) or small (<10 mm). We used a Cox proportional hazards regression model to calculate the hazard ratios (HRs) of CRC incidence, after adjusting for various potential risk factors.ResultsAfter a median follow-up period of 10 years, we documented 491 incident cases of CRC: 51 occurred in 6161 participants with conventional adenomas, 24 in 5918 participants with serrated polyps, and 427 in 112,107 participants with no polyp. Compared with participants with no polyp detected during initial endoscopy, the multivariable HR for incident CRC in individuals with an advanced adenoma was 4.07 (95% confidence interval [CI] 2.89-5.72) and the HR for CRC in individuals with a large serrated polyp was 3.35 (95% CI 1.37-8.15). In contrast, there was no significant increase in risk of CRC in patients with nonadvanced adenomas (HR 1.21; 95% CI 0.68-2.16, P = .52) or small serrated polyps (HR 1.25; 95% CI 0.76-2.08; P = .38).ConclusionsThese findings provide support for guidelines that recommend repeat lower endoscopy within 3 years of a diagnosis of advanced adenoma and large serrated polyps. In contrast, patients with nonadvanced adenoma or small serrated polyps may not require more intensive surveillance than patients without polyps.

Project description:Background & aimsSerrated polyps (SPs) and conventional adenomas are precursor lesions for colorectal cancer (CRC), but they are believed to arise via distinct pathways. We characterized risk factor profiles for SPs and conventional adenomas in a post hoc analysis of data from 3 large prospective studies.MethodsWe collected data from the Nurses' Health Study, the Nurses' Health Study 2, and the Health Professionals Follow-up Study on subjects who developed SPs or conventional adenomas. Our analysis comprised 141,143 participants who had undergone lower gastrointestinal endoscopy, provided updated diet and lifestyle data every 2-4 years, and were followed until diagnosis of a first polyp. We assessed 13 risk factors for CRC in patients with SPs or conventional adenomas and examined the associations according to histopathology features.ResultsWe documented 7945 SPs, 9212 conventional adenomas, and 2382 synchronous SPs and conventional adenomas during 18-20 years of follow-up. Smoking, body mass index, alcohol intake, family history of CRC, and height were associated with higher risk of SPs and conventional adenomas, whereas higher intake of vitamin D and marine omega-3 fatty acid were associated with lower risk. The associations tended to be stronger for synchronous SPs and conventional adenomas. Smoking, body mass index, and alcohol intake were more strongly associated with SPs than conventional adenomas (P for heterogeneity <.05), whereas physical activity and intake of total folate and calcium were inversely associated with conventional adenomas but not SPs. For SPs and conventional adenomas, the associations tended to be stronger for polyps in the distal colon and rectum, of 10 mm or larger or with advanced histology.ConclusionsIn an analysis of data from 3 large prospective studies, we found that although SPs and conventional adenomas share many risk factors, some factors are more strongly associated with one type of lesion than the other. These findings provide support for the etiologic heterogeneity of colorectal neoplasia.

Dataset Information

Colorectal cancer susceptibility variants and risk of conventional adenomas and serrated polyps: results from three cohort studies.

Background

Methods

Results

Conclusions

Publications

Colorectal cancer susceptibility variants and risk of conventional adenomas and serrated polyps: results from three cohort studies.

Similar Datasets

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