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Background: Oral contraceptives (OC) are associated with a decreased risk of colorectal cancers; however, a recent study reported an increased risk of small colorectal adenomas associated with OC use. To determine if these results were replicable in a different study population, we investigated the relationship between OC use and other reproductive factors and risk of colorectal polyps in a case-control study in western Washington.Methods: Study participants were 24-79-year-old female enrollees at an integrated health care system in western Washington who were diagnosed as having adenomas (n = 299), serrated polyps (n = 337), both types of polyps (n = 105) or as polyp-free controls (n = 615) through an index colonoscopy and completed a structured interview to collect reproductive history information. Multivariable polytomous logistic regression was used to compare case groups to controls and to each other; odds ratios (OR) and 95% confidence intervals were estimated.Results: There was no association between OC use, duration of use, or recency of use and the risk of either adenomas or serrated polyps [adjusted OR for OC ever use (95% CI) 0.85 (0.58-1.23) and 0.96 (0.66-1.40), respectively], and associations did not differ by lesion severity within the adenoma or serrated pathways. Further, no associations were observed between other reproductive factors and risk of colorectal polyp subtypes.Conclusions: Our results suggest that reproductive factors, including OC use, are not associated with early colorectal cancer precursor lesions. [ABSTRACT FROM AUTHOR]

We conducted a case-control study of the association between subsets of colorectal polyps, including adenomas and serrated polyps, and single-nucleotide polymorphisms (SNPs) related to colorectal cancer through prior genome-wide association studies (GWAS). Participants were enrollees in the Group Health Cooperative (Seattle, Washington) aged 24–79 years who received a colonoscopy from 1998 to 2007, donated a buccal or blood sample, and completed a structured questionnaire. We performed genotyping of 13 colorectal cancer susceptibility SNPs. Polytomous logistic regression models were used to estimate odds ratios and 95% confidence intervals for associations between polyps and the colorectal cancer risk allele for each SNP under a log-additive model. Analyses included 781 controls, 489 cases with adenoma, 401 cases with serrated polyps, and 188 cases with both polyp types. The following SNPs were associated with advanced adenomas: rs10936599, rs10795668, rs16892766, and rs9929218 (P < 0.05). For nonadvanced adenomas and for serrated polyps overall, only rs961253 was statistically significant (P < 0.05). These associations were in the same directions as those in prior colorectal cancer GWAS. No SNP was significantly associated with hyperplastic polyps, and only rs6983267 was significantly associated with sessile serrated polyps, but this association was opposite of that found in colorectal cancer GWAS. Our results suggest that the association between colorectal cancer susceptibility SNPs and colorectal polyps varies by polyp type. [ABSTRACT FROM PUBLISHER]

Using a case-control design, we evaluated differences in risk factors for colorectal polyps according to histological type, anatomical site, and severity. Participants were enrollees in the Group Health Cooperative aged 20–79 years who underwent colonoscopy in Seattle, Washington, between 1998 and 2007 and comprised 628 adenoma cases, 594 serrated polyp cases, 247 cases with both types of polyps, and 1,037 polyp-free controls. Participants completed a structured interview, and polyps were evaluated via standardized pathology review. We used multivariable polytomous logistic regression to compare case groups with controls and with the other case groups. Factors for which the strength of the association varied significantly between adenomas and serrated polyps were sex (P < 0.001), use of estrogen-only postmenopausal hormone therapy (P = 0.01), and smoking status (P < 0.001). For lesion severity, prior endoscopy (P < 0.001) and age (P = 0.05) had significantly stronger associations with advanced adenomas than with nonadvanced adenomas; and higher education was positively correlated with sessile serrated polyps but not with other serrated polyps (P = 0.02). Statistically significant, site-specific associations were observed for current cigarette smoking (P = 0.05 among adenomas and P < 0.001 among serrated polyps), postmenopausal estrogen-only therapy (P = 0.01 among adenomas), and obesity (P = 0.01 among serrated polyps). These findings further illustrate the epidemiologic heterogeneity of colorectal neoplasia and may help elucidate carcinogenic mechanisms for distinct pathways. [ABSTRACT FROM PUBLISHER]

Purpose: BRAF mutation and DNA hypermethylation have linked sessile serrated adenomas/polyps (SSA/Ps) to serrated colorectal cancer (CRC) in cross-sectional studies, but they have not been evaluated in a longitudinal study. We aimed to evaluate the associations between molecular markers of serrated polyps and subsequent advanced colorectal neoplasia.Methods: Study subjects included Kaiser Permanente Washington members aged 20-75 years who received an index colonoscopy between 1/1/1998 and 12/31/2007 and had hyperplastic polyps (HPs) or SSA/Ps according to study pathology review. Polyps from index colonoscopies were removed and assayed for BRAF mutation, CpG island methylator phenotype (CIMP), and MLH1 methylation. Pathology reports and biopsies from the subsequent lower gastrointestinal endoscopy through 1/1/2013 were reviewed for advanced colorectal neoplasia. We identified additional incident CRC cases through linkage to the Seattle-Puget Sound Surveillance Epidemiology and End Results registry. We used generalized estimating equations to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for subsequent advanced colorectal neoplasia, comparing index serrated polyps with different molecular markers.Results: We included 553 individuals with index serrated polyps (420 HPs and 133 SSA/Ps) and 795 subsequent endoscopies. The prevalence of BRAF-mutant, CIMP-high, and MLH1-methylated serrated polyps were 51%, 4%, and 2%, respectively. BRAF and CIMP were not associated with subsequent advanced colorectal neoplasia. MLH1-methylated SSP/As were significantly more likely to have subsequent advanced neoplasia (OR = 4.66, 95% CI 1.06-20.51).Conclusion: Our results suggest that BRAF-mutant and CIMP-high serrated polyps are not associated with subsequent advanced colorectal neoplasia. Among SSA/Ps, MLH1 methylation may be an important marker to identify high-risk CRC precursors. [ABSTRACT FROM AUTHOR]