Risk Of Conventional Adenomas Research Articles

Independent and joint associations of general and abdominal obesity with the risk of conventional adenomas and serrated polyps: A large population-based study in East Asia.

Evidence regarding associations of general and abdominal obesity with the risk of conventional adenomas (ADs) and serrated polyps (SPs) from Asian population is scarce. Our study aimed to investigate the independent and joint associations of general obesity assessed by body mass index (BMI) and abdominal obesity assessed by waist circumference (WC) or waist-to-hip ratio (WHR) with the risk of ADs and SPs among 25 222 participants recruited by a population-based screening program. Compared to participants with normal BMI, those with a BMI ≥28 kg/m2 had increased risk of ADs (odds ratio [OR] 1.52, 95% confidence interval [CI]: 1.36-1.70) and SPs (OR 1.69, 95% CI: 1.38-2.07). For participants with a WC ≥102 cm (≥88 cm for females), the risk of ADs (OR 1.37, 95% CI: 1.25-1.51) and SPs (OR 1.81, 95% CI: 1.52-2.16) was higher than that of the reference group. For participants with a WHR ≥0.95 (≥0.90 for females), the risk of ADs (OR 1.26, 95% CI: 1.16-1.36) and SPs (OR 1.46, 95% CI: 1.26-1.69) was higher than that of the reference group. Moreover, participants with both BMI ≥28 kg/m2 and WC ≥102 cm (≥88 cm for females) had 61% and 119% higher risk of ADs (OR 1.61, 95% CI: 1.39-1.85) and SPs (OR 2.19, 95% CI: 1.70-2.82) compared to those with both normal BMI and WC. These findings indicate that both general and abdominal obesity are associated with SPs and ADs, presenting stronger association with SPs than ADs. Moreover, the association is more evident when both obesities exist.

Healthy lifestyle and the risk of conventional adenomas and serrated polyps: Findings from a large colonoscopy screening population.

Evidence on the link between healthy lifestyle and colorectal cancer (CRC) precursors is limited. Our study aimed to examine and compare the associations of healthy lifestyle with CRC precursors in adenoma (AD)-carcinoma and serrated pathways. A total of 24 480 participants including 6309 ADs, 1343 serrated polyps (SPs), and 16 828 polyp-free controls were included. A healthy lifestyle score (HLS) was constructed based on five lifestyle factors including cigarette smoking, alcohol drinking, physical activity, diet and body weight, and categorized into least, slightly, moderately and most healthy. Multivariable logistic regressions were used to estimate odds ratio (OR) and 95% confidence interval (CI). Inverse dose-response associations between the HLS and risk of ADs were observed (OR per 1 score increment for ADs: 0.82 [95% CI 0.79-0.84]; for SPs: 0.73 [95% CI 0.69-0.78]), and the association with SPs was more evident than with ADs (OR 0.90, 95% CI 0.85-0.96). Compared to participants with the least healthy lifestyle, those with the most healthy lifestyle had 47% lower risk of ADs (OR 0.53, 95% CI 0.47-0.59) and 70% lower risk of SPs (OR 0.30, 95% CI 0.23-0.39), respectively. These inverse associations were consistent across lesion stage and anatomic subsite and not modified by any stratification factors. The risk advancement periods for the most vs the least healthy lifestyle were -9.49 years for ADs and -20.69 years for SPs. Our findings help confirm the preventive role of healthy lifestyle in colorectal carcinogenesis.

Gallstone Disease and Risk of Conventional Adenomas and Serrated Polyps: A Prospective Study.

Gallstone disease has been associated with colorectal cancer and some form of polyps, although the findings are inconclusive. It remains unknown whether gallstone disease influences the initiation of colorectal cancer. We prospectively assessed the association of gallstone disease with risk of colorectal cancer precursors, including conventional adenomas and serrated polyps, in the Nurses' Health Study (1992-2012), the Nurses' Health Study II (1991-2011), and the Health Professionals Follow-up Study (1992-2012). Gallstone diseases were assessed using biennial follow-up questionnaires. Self-reported polyp diagnosis was confirmed by review of medical records. Logistic regression models were used to calculate the ORs with adjustment for smoking and other potential confounders. Among participants who had undergone a total of 323,832 endoscopies, 16.5% had gallstone disease and 11.3% received cholecystectomy. We documented 1,724, 1,212, and 1,943 cases of conventional adenomas and 1,470, 1,090, and 1,643 serrated polyps in patients with gallstones, cholecystectomy, and either of them, respectively. The OR for adenomas was 1.00 [95% confidence interval (CI): 0.95-1.06] for gallstones, 0.99 (95% CI, 0.93-1.06) for cholecystectomy, and 1.00 (95% CI, 0.95-1.05) for either exposure. The corresponding ORs for serrated polyps were 0.98 (95% CI, 0.92-1.04), 0.99 (95% CI, 0.93-1.06), and 0.97 (95% CI, 0.92-1.03), respectively. Gallstone disease is not associated with colorectal polyps. Patients with gallstones appear to have similar risk of colorectal polyps compared with those without and may therefore follow average-risk colorectal cancer screening guidelines.

Genetic Obesity Variants and Risk of Conventional Adenomas and Serrated Polyps.

Higher body mass index (BMI) is associated with increased risk of colorectal cancer. How genetically predicted BMI may be associated with colorectal cancer precursors is unknown. Our objective was to quantify the association of genetically predicted and measured BMI with risk of colorectal cancer precursors. We evaluated the association of genetically predicted and measured BMI with risk of conventional adenomas, serrated polyps, and synchronous polyps among 27,426 participants who had undergone at least one lower gastrointestinal endoscopy in the Nurses' Health Study, Nurses' Health Study II, and Health Professionals Follow-up Study. Genetic risk score was derived from 97 BMI-related single nucleotide polymorphisms. Multivariable logistic regression evaluated each polyp subtype compared to non-polyps. For conventional adenomas, the OR per 2-kg/m2 increase was 1.03 (95% CI, 1.01-1.04) for measured BMI and 0.98 (95% CI, 0.88-1.10) for genetically predicted BMI; for serrated polyps, the OR was 1.06 (95% CI, 1.04-1.08) and 1.04 (95% CI, 0.90-1.20), respectively; for synchronous polyps, the OR was 1.10 (95% CI, 1.07-1.13) and 1.09 (95% CI, 0.89-1.34), respectively. Genetically predicted BMI was associated with synchronous polyps in women (OR = 1.37, 95% CI: 1.05-1.79). Genetically predicted BMI was not associated with colorectal cancer precursor lesions. The confidence intervals were wide and encompassed those for measured BMI, indicating that null findings may be due to insufficient power.

Antibiotic Use Associated With Risk of Colorectal Polyps in a Nationwide Study

Use of antibiotics affects the composition of the microbiome and might affect development of colorectal polyps, which are precursors to colorectal cancer. We performed a nested case-control study in Sweden of 45,744 patients with a colorectal polyp (cases) in the nationwide gastrointestinal ESPRESSO histopathology cohort, using unaffected full siblings as controls (n= 93,307). Polyps were classified by morphology SnoMed codes into conventional adenomas and serrated polyps. Through linkage to the Prescribed Drug Register, we assessed use and cumulative dispensations of antibiotic until 1 year prior to polyp diagnosis for cases and their sibling controls. During a median study period of 6.9 years, compared with non-users, users of antibiotics (including 28,884 cases [63.1%] and 53,222 sibling controls [57.0%]) had a higher risk of colorectal polyps (odds ratio [OR], 1.08; 95% CI, 1.04-1.13). Risk increased with higher number of dispensations (OR for ≥ 6 dispensations, 1.33; 95% CI, 1.25-1.43) (Ptrend < .0001). We observed a stronger association with polyps for broad-spectrum antibiotics (OR comparing users to non-users, 1.23; 95% CI, 1.18-1.29) than for narrow-spectrum antibiotics (OR, 1.05; 95% CI, 1.01-1.10), and for tetracyclines and quinolones (OR, 1.21) than penicillin and other classes (ORs ranged from 1.04 to 1.16). The findings remained robust with several sensitivity analyses, including use of a 2-year lead-in period for antibiotic assessment and correction for misclassification in controls. Use of broad-spectrum antibiotics was more strongly associated with risk of serrated polyps (OR, 1.29; 95% CI, 1.21-1.38) compared with risk of conventional adenomas (OR, 1.17; 95% CI, 1.11-1.24). We found no differences in risk of colon vs rectal polyps with antibiotic use (Pheterogeneity > .10). We found stronger associations for younger (<50 years) vs older adults (≥50 years) for users of quinolones, sulfonamides, trimethoprim, and cephalosporins (Pinteraction < .001). In a nationwide case-control study in Sweden, after accounting for hereditary and early life environmental factors, antibiotic use was associated with increased risk of colorectal polyps. Our findings indicate a role for intestinal dysbiosis in early stages of colorectal carcinogenesis.

Abstract 964: The association of meat intake, meat cooking methods, and meat-derived mutagen exposure with the risk of sessile serrated polyps

Abstract Colorectal polyps are the precursors of colorectal cancer, the second leading cause of cancer death in the United States. Red and processed meat intakes have been associated with an increased risk of conventional colorectal adenomas and are classified as carcinogens by the World Health Organization. The mechanism for the relationship between red and processed meat intakes and adenoma risk remains unclear. An explanation may be the exposure to mutagens derived from meat including heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are formed by cooking meats at high temperatures. Although intakes of these meats and mutagens has been associated with risks of conventional adenomas including in our study, no previous study has evaluated risk of sessile serrated polyp (SSPs). SSPs, a more recently recognized precursor lesion for microsatellite instable cancer, were strongly associated with red meat intake in our earlier study. This new study builds on that work by evaluating the associations between meat intake, meat cooking methods, and meat mutagens with risks of SSPs and compares the risks to conventional adenomas and hyperplastic polyps. The analysis is conducted in the Tennessee Colorectal Polyp Study, using polytomous logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). Dietary information was collected by a self-administered food frequency questionnaire and telephone interview to ascertain meat intake and doneness. This information was used to estimate the intakes of meats, well-done meats, PAHs, HCAs, and mutagenic activity. Several measures of meat intake were strongly associated with risk of SSPs. Highest quartile levels of total meat intake (OR=2.04; 95% CI: 1.24-3.36, p for trend=0.002), red meat intake (OR=2.32; 95% CI: 1.37-3.91, p for trend&amp;lt;0.001), processed meat intake (OR=1.99, 95% CI: 1.24-3.20, p for trend=0.004), well-done red meat (OR=2.13, 95% CI: 1.28-3.55, p for trend=0.002), well-done processed meat (OR=1.60, 95% CI: 1.06-2.4, p for trend=0.03), and the HCA MeIQx (OR=2.55, 95% CI: 1.50-4.33, p for trend=0.003) were associated with statistically significantly increased risks of SSP in comparison to the lowest intake levels. Most of these associations were stronger for risk of SSP than for the other types of polyps. In particular, MeIQx intake was not associated with risk of conventional adenomas suggesting that the mechanisms by which red meat intake affects polyp risk may be different between the conventional adenoma and serrated pathways. Future studies are needed to confirm the relationship between meat and meat mutagen intake with SSP risk and to further define the mechanism(s) by which intake of these factors affects SSP risk. Citation Format: Dominique A. Mosley, Harvey J. Murff, Reid M. Ness, Walter E. Smalley, Wei Zheng, Martha J. Shrubsole. The association of meat intake, meat cooking methods, and meat-derived mutagen exposure with the risk of sessile serrated polyps [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 964.

Abstract LB-249: Marine omega-3 fatty acid supplementation and risk of colorectal adenomas and serrated polyps: A randomized placebo-controlled trial

Abstract BACKGROUND Marine omega-3 fatty acid (MO3FA) has been suggested to protect against colorectal cancer. However, the chemopreventive effect of MO3FA on precursors of colorectal cancer remains unclear. METHODS We assessed the effect of MO3FA supplementation on risk of conventional adenomas and serrated polyps, the two distinct subtypes of precursors of colorectal cancer, within the VITamin D and OmegA-3 TriaL (VITAL), a randomized, placebo-controlled, two-by-two factorial trial of MO3FA (1 g per day [460 mg EPA and 380 mg DHA]) and vitamin D3 (2000 IU per day) supplements among 25,871 Americans aged 50 years or older (including 5,106 blacks). Although regular screening endoscopy was not protocol-mandated during the study period, prior colonoscopy/sigmoidoscopy and other risk factors were well balanced by treatment group at baseline. When participants reported a diagnosis of polyp on the annual follow-up questionnaire, we requested permission to obtain endoscopic and pathologic records to confirm the diagnosis and extract the histopathologic information. Serrated polyps included hyperplastic polyps and mixed/serrated adenomas (traditional and sessile types). We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) in relation to MO3FA treatment using logistic regression, after adjusting for age, sex, vitamin D treatment assignment, and use of endoscopy. We also performed subgroup analyses according to polyp features and participants’ characteristics. RESULTS During a median follow-up of 5.3 years, we documented 296 cases of colorectal adenomas in the intervention group and 306 in the control groups (multivariable OR=0.97, 95% CI, 0.83-1.14); and 178 and 170 cases of serrated polyps in the two groups, respectively (OR=1.05, 95% CI, 0.85-1.30). Similar null association was found for advanced adenomas (advanced histology or ≥10 mm) or high-risk serrated polyps (located in the proximal colon or ≥10 mm), or polyp subgroups according to size, location, multiplicity, or histology. When stratified by race/ethnicity, we found that MO3FA treatment was associated with lower risk of adenomas (OR=0.53, 95% CI, 0.31-0.91) and serrated polyps (OR=0.54, 95% CI, 0.27-1.10) in African Americans, whereas no association was found in non-Hispanic whites or other racial/ethnic groups (P for interaction=0.06 for adenomas and 0.15 for serrated polyps). No interaction was detected with other demographic factors, colorectal cancer risk factors, endoscopic use, baseline fish intake, or plasma MO3FA levels. CONCLUSIONS Supplementation with marine omega-3 fatty acids at a dose of 1 g per day was not associated with risk of colorectal premalignant lesions. A potential benefit among African Americans requires further confirmation. Citation Format: Mingyang Song, I-Min Lee, JoAnn E. Manson, Julie E. Buring, Rimma Dushkes, David Gordon, Joseph Walter, Kana Wu, Andrew T. Chan, Shuji Ogino, Charles S. Fuchs, Jeffrey A. Meyerhardt, Edward L. Giovannucci. Marine omega-3 fatty acid supplementation and risk of colorectal adenomas and serrated polyps: A randomized placebo-controlled trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-249.

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

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

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

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. Among 27426 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. 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). 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.

Abstract B85: Racial differences in the risk of serrated polyps and conventional adenomas in a younger aged, uninsured population in South Carolina

Abstract Compared to European Americans (EA), African Americans (AA) have higher colorectal cancer (CRC) incidence and are diagnosed with CRC at younger ages. The reasons for these disparities are poorly understood, but one contributing factor could be reduced access to high-quality preventative care. To address CRC disparities, this study assessed whether a racial difference in risk of large bowel polyps (precursors to most CRC) persists within a younger-aged, uninsured population in South Carolina (SC) undergoing screening colonscopy. We analyzed data from a multi-site statewide CRC screening program in SC to explore the risk of large bowel polyps among AA and EA. Eligible patients were uninsured, asymptomatic, had no personal history of colorectal neoplasia, and were between the ages 45-64 years (AA) or 50-64 years (EA). Using generalized linear regression, we estimated risk ratios and 95% confidence intervals (CI) as measures of the association between race and risk for one or more conventional adenomas or serrated polyps adjusting for age, sex, family history of CRC, and clinical site. Serrated polyps (SP) were defined as one or more hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed adenomatous polyps. SP were first classified in a single category since not all project pathologists used up-to-date pathologic terminology and there was a high-level of variability among clinical sites in use of newer SP categories (i.e., sessile, traditional adenomas). Serrated adenomas included any SP with serrated adenomatous features (sessile, traditional, or mixed). Advanced SP were defined as SP with large size (an estimated ≥ 1 cm). Conventional adenomas (CA) were defined as tubular, tubulovillous, or villous polyps. Advanced CA were defined as adenomas with at least 25% villous component (TVA), high-grade dysplasia (HGD), or large size. We also stratified polyps separately according to colonic region (proximal or distal colorectum), large size, and advanced CA histology (TVA, HGD). Of the 237 subjects enrolled (127 AA, 91 EA, 19 other), 233 had a complete exam (i.e., to the cecum). Our results suggested a lower risk of SP among AA compared to EA: any SP (RR 0.50 (95% CI 0.30-0.84)), any serrated adenoma (RR 0.35 (95% CI 0.11-1.14)), and any large SP (RR 0.27 (95% CI 0.09-0.85)). Although not always statistically significant, the trend in the results indicate that the risk of CA was higher in AA compared to EA: any CA 1.17 (95% CI 0.77-1.79), large CA 2.16 (95% CI 0.70-6.66), proximal large CA 4.24 (95% CI 1.0-18.01), and any advanced CA 1.38 (95% CI 0.55-3.42). In patients under 55 years of age (median age), AA compared to EA had higher risk of advanced CA histology lesions RR 4.11 (95% 1.05 -16.11), but otherwise risks were similar in the age groups. Overall, our findings suggest that it is important to consider type of polyp and age when assessing risk in different racial groups. Our results in this unique study population are consistent with an earlier study showing that AA have a lower risk of metachronous SP and among younger patients, an increased risk of conventional adenomas, especially advanced lesions. The persistence of these observations within a study population comprised of all medically underserved individuals implies that the unique features of the epidemiology of colorectal neoplasia in AA cannot be completely attributed to access to care barriers. Citation Format: Kristin Wallace, Anthony Alberg, Bridgette Blankenship, Heather Brandt, Renay Caldwell, James Dunn, Patricia Hegedus, Brenda Hoffman, Courtney Marsh, March Seabrook, Marylou Stinson, Annie Thibault, Franklin Berger. Racial differences in the risk of serrated polyps and conventional adenomas in a younger aged, uninsured population in South Carolina. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B85.