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To evaluate whether limited participation in life activities is associated with quality of life (QOL) in rectal cancer survivors, and if so, whether this association is independent of bowel function difficulties. We surveyed rectal cancer survivors from four healthcare systems about their QOL, bowel function, and participation in life activities. Additional demographic and clinical variables were extracted from the electronic health record. We examined independent associations between bowel function, participation in life activities, and QOL, controlling for potential confounders. We also identified factors, including ostomy status, that correlate with participation in life activities. Of the 527 respondents, 52% were male, 80% were non-Hispanic white, and the mean age was 63. In fully adjusted models for all rectal cancer survivors, participation in life activities was positively associated with QOL, while bowel function was not. Bowel function retained an independent association with QOL for those who previously had an ostomy and were therefore more likely to have a low rectal anastomosis. Lower participation in life activities was correlated with lower self-reported physical and cognitive function, younger age, financial difficulty, and being non-Hispanic white. Rectal cancer survivors’ participation in life activities was strongly associated with QOL, even when controlling for numerous confounders, including bowel function. Identifying ways to improve participation in life activities may be critical to developing rehabilitative and other supportive interventions that optimize QOL among rectal cancer survivors.

Rising trends in the incidence and mortality of early-onset colorectal cancer (CRC) in those who are younger than 50 years have been well established. These trends have spurred intense investigation focused on elucidating the epidemiology and characteristics of early-onset CRC, as well as on identifying strategies for early detection and prevention. In this review, we provide a contemporary update on early-onset CRC with a particular focus on epidemiology, molecular characterization, red flag signs and symptoms, and screening for early-onset CRC.

Background: Relatively little is known about factors associated with long-term survival (LTS) following a diagnosis of ovarian cancer. Methods: We conducted a retrospective study of high-grade serous ovarian cancer (HGSOC) to explore predictors of LTS (defined as ≥7 years of survival) using electronic medical record data from a network of integrated health care systems. Multivariable logistic regression with forward selection was used to compare characteristics of women who survived ≥7 years after diagnosis (n = 148) to those who died within 7 years of diagnosis (n = 494). Results: Our final model included study site, age, stage at diagnosis, CA-125, comorbidity score, receipt of chemotherapy, BMI, and four separate comorbid conditions: weight loss, depression, hypothyroidism, and liver disease. Of these, only younger age, lower stage, and depression were statistically significantly associated with LTS. Conclusions: We did not identify any new characteristics associated with HGSOC survival. Impact: Prognosis of ovarian cancer generally remains poor. Large, pooled studies of ovarian cancer are needed to identify characteristics that may improve survival.

Background Cardiovascular medications may be associated with cancer development, but little is known about their association with cancer recurrence. Medications such as statins and antihypertensives may be commonly used among colon cancer survivors, who are, on average, diagnosed in their mid-60s. We described the associations between statins and antihypertensive medications and colon cancer recurrence in a large, population-based study. Methods We conducted a cohort study among adults with stage I-IIIA colon cancer diagnosed in 1995–2014 in two Kaiser Permanente regions, Colorado and Washington. Statin and antihypertensive use were obtained from electronic pharmacy dispensing data. People were classified as medication users on the date of their first dispensing after cohort entry, which started 90 days after completing cancer treatment, continuing through the earliest of death, health plan disenrollment, or chart abstraction. We collected outcome information from medical record abstraction and tumor registries on colon cancer recurrences and second primary cancers. Using Cox proportional hazards multivariable models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for colon cancer recurrences and any cancer event (recurrences and new primaries at any anatomic site) comparing medication users to non-users. Results Among 2039 people, 937 (46%) used statins and 1425 (70%) used antihypertensives at any point during a median of 4.9 years of follow-up; 460 people had any additional cancer event, including 152 with a colon cancer recurrence. Statin use was not associated with colon cancer recurrence (HR = 1.09, 95%CI = 0.65–1.85) or any cancer event (HR = 1.12, 95%CI = 0.85–1.47), nor was antihypertensive use associated with recurrence (HR = 0.73, 95%CI = 0.44–1.21) or any cancer event (HR = 0.93, 95%CI = 0.70–1.24). Conclusions Our results suggest no association between cardiovascular medication use and the risk of recurrence or any additional cancer, and may provide reassurance to colon cancer survivors.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P, Reporting Summary. Further information on experimental design is available in the Life Sciences Reporting Summary linked to this article.

Simple Summary Around 70% of colorectal cancer patients report having sleeping issues, and identifying whether anatomic site plays a significant factor in sleep quality is important. The aim of our population-based study was to assess differences in sleep between rectal and colon cancer patients. We identified that rectal cancer patients were more likely to have sleep complications, such as changes in sleep patterns after diagnosis, getting up to use the bathroom, and pain, compared to colon cancer patients. Identifying whether anatomic colorectal cancer site affects sleep quality and sleep-related issues suggests that sleep-focused survivorship care may be suggested for rectal cancer patients to ensure patients receive appropriate support. Abstract Purpose: Sleep quality in relation to anatomic site among colorectal cancer (CRC) patients is not well understood, though discerning the relationship could contribute to improved survivorship care. Methods: We ascertained sleep quality (Pittsburgh Sleep Quality Index) and other personal characteristics within an ongoing population-based study of CRC patients identified through a cancer registry (N = 1453). Differences in sleep quality by CRC site were analyzed using chi-square and ANOVA tests. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of tumor site with sleep quality concerns, adjusting for patient attributes and time since diagnosis. Results: Sleeping problems were reported by 70% of CRC patients. Overall, participants with rectal (vs. colon) cancer were more likely (OR (95% CI)) to report general trouble sleeping (1.58 (1.19, 2.10)). Rectal cancer patients were also more likely than colon cancer patients to report changes in sleep patterns after cancer diagnosis (1.38 (1.05, 1.80)), and trouble sleeping specifically due to getting up to use the bathroom (1.53 (1.20, 1.96)) or pain (1.58 (1.15, 2.17)), but were less likely to report trouble sleeping specifically due to issues with breathing/coughing/snoring (0.51 (0.27, 0.99)). Conclusion: Overall, rectal cancer patients were more likely to have sleep complications compared to colon cancer patients. This suggests sleep-focused survivorship care may be adapted according to CRC site to ensure patients receive appropriate support.

PurposeThis study aimed to characterize patient and clinical factors associated with cannabis(marijuana) use among patients diagnosed with colorectal cancer (CRC).MethodsWe identified CRC patients, diagnosed from 2016-2018, using the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. CRC patients were recruited via mail and telephone, and participants completed a questionnaire eliciting information on medical history, demographics, and lifestyle factors, including cannabis use. Cancer stage was obtained from SEER registry data.ResultsOf 1,433 survey respondents, 339 (24%) were current cannabis users. Current cannabis use was associated with younger age at diagnosis, lower BMI, and a higher prevalence of cigarette smoking and alcohol consumption (P-value

International audience; Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08 95% CI: 1.00, 1.17 P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12 95% CI: 1.03, 1.21 P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98 95% CI: 0.96, 1.00 P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.

ObjectiveAn understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for sporadic CRC differs by anatomical subsite of the primary tumor has not been examined.DesignTo identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48,214 CRC cases and 64,159 controls of European ancestry. We characterized effect heterogeneity at CRC risk loci using multinomial modeling.ResultsWe identified 13 loci that reached genome-wide significance (P−8) and that were not reported by previous GWAS for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer.ConclusionGenetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumor.Significance of this studyWhat is already known about this subject?Heterogeneity among colorectal cancer (CRC) tumors originating at different locations of the colorectum has been revealed in somatic genomes, epigenomes, and transcriptomes, and in some established environmental risk factors for CRC.Genome-wide association studies (GWAS) have identified over 100 genetic variants for overall CRC risk; however, a comprehensive analysis of the extent to which genetic risk factors differ by the anatomical sublocation of the primary tumor is lacking.What are the new findings?In this large consortium-based study, we analyzed clinical and genome-wide genotype data of 112,373 CRC cases and controls of European ancestry to comprehensively examine whether CRC case subgroups defined by anatomical sublocation have distinct germline genetic etiologies.We discovered 13 new loci at genome-wide significance (P−8) that were specific to certain anatomical sublocations and that were not reported by previous GWAS for overall CRC risk; multiple lines of evidence support strong candidate target genes at several of these loci, including PTGER3, LCT, MLH1, CDX1, KLF14, PYGL, BCL11B, and BMP7.Systematic heterogeneity analysis of genetic risk variants for CRC identified thus far, revealed that the genetic architectures of proximal and distal CRC are partly distinct.Taken together, our results further support the idea that tumors arising in different anatomical sublocations of the colorectum may have distinct etiologies.How might it impact on clinical practice in the foreseeable future?Our results provide an informative resource for understanding the differential role that genes and pathways may play in the mechanisms of proximal and distal CRC carcinogenesis.The new insights into the etiologies of proximal and distal CRC may inform the development of new precision prevention strategies, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention.Our findings suggest that future studies of etiological risk factors for CRC and molecular mechanisms of carcinogenesis should take into consideration the anatomical sublocation of the colorectal tumor.

BACKGROUND AND AIMS: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. METHODS: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (TCGA, n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted. RESULTS: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10(−6), including genes in four novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In nine known GWAS-identified loci, we uncovered nine genes that have not been previously reported, whereas four genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < 0.01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis. CONCLUSION: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.

Summary: Homozygotes for the higher penetrance hemochromatosis risk allele, HFE c.845G>A (p.Cys282Tyr, or C282Y), have been reported to be at a 2- to 3-fold increased risk for colorectal cancer (CRC). These results have been reported for small sample size studies with no information about age at diagnosis for CRC. An association with age at diagnosis might alter CRC screening recommendations. We analyzed two large European ancestry datasets to assess the association of HFE genotype with CRC risk and age at CRC diagnosis. The first dataset included 59,733 CRC or advanced adenoma cases and 72,351 controls from a CRC epidemiological study consortium. The second dataset included 13,564 self-reported CRC cases and 2,880,218 controls from the personal genetics company, 23andMe. No association of the common hereditary hemochromatosis (HH) risk genotype and CRC was found in either dataset. The odds ratios (ORs) for the association of CRC and HFE C282Y homozygosity were 1.08 (95% confidence interval [CI], 0.91–1.29; p = 0.4) and 1.01 (95% CI, 0.78–1.31, p = 0.9) in the two cohorts, respectively. Age at CRC diagnosis also did not differ by HFE C282Y/C282Y genotype in either dataset. These results indicate no increased CRC risk in individuals with HH genotypes and suggest that persons with HH risk genotypes can follow population screening recommendations for CRC.

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.

BACKGROUND: Lung cancer screening (LCS) requires complex processes to identify eligible patients, provide appropriate follow-up, and manage findings. It is unclear whether LCS in real-world clinical settings will realize the same benefits as the National Lung Screening Trial (NLST). OBJECTIVE: To evaluate the impact of process modifications on compliance with LCS guidelines during LCS program implementation, and to compare patient characteristics and outcomes with those in NLST. DESIGN: Retrospective cohort study. SETTING: Kaiser Permanente Colorado (KPCO), a non-profit integrated healthcare system. PATIENTS: A total of 3375 patients who underwent a baseline lung cancer screening low-dose computed tomography (S-LDCT) scan between May 2014 and June 2017. MEASUREMENTS: Among those receiving an S-LDCT, proportion who met guidelines-based LCS eligibility criteria before and after LCS process modifications, differences in patient characteristics and outcomes between KPCO LCS patients and the NLST cohort, and factors associated with a positive screen. RESULTS: After modifying LCS eligibility confirmation processes, patients receiving S-LDCT who met guidelines-based LCS eligibility criteria increased from 45.6 to 92.7% (P

Background: As more states legalize cannabis for medical and recreational use, people increasingly use cannabis to treat medical conditions and associated symptoms. The prevalence and utility of cannabis for cancer-related symptoms may be clarified by examining cannabis use among patients with a common cancer diagnosis. We aimed to determine the prevalence of cannabis use among colorectal cancer (CRC) survivors and its associations with quality of life (QoL) and cancer-related symptomatology. Methods: A cross-sectional survey of patient-reported QoL outcomes and behaviors, including cannabis use, was conducted within the Patient Outcomes To Advance Learning network’s (PORTAL) CRC Cohort. The cohort included a population-based sample of healthcare system members ≥ 18 years old diagnosed with adenocarcinoma of the colon or rectum from 2010 through 2016. We assessed the association between cannabis use and QoL using the European Organization for Research and Treatment of Cancer QLQ-C30 summary score. Results: Of the 1,784 respondents, 293 (16.4%) reported cannabis use following CRC diagnosis. Current tobacco smokers were more likely to use cannabis compared to former or never tobacco smokers (adjusted odds ratio [aOR] 2.71, 95% CI 1.56 to 4.70). Greater alcohol use (> 4 drinks per month versus ≤ 4 drinks per month) was associated with cannabis use (aOR 2.17, 95% CI 1.65 to 2.85). There was an association between cannabis use and cancer stage at diagnosis, with stage 3 or 4 CRC patients more likely to use cannabis than stage 1 or 2 CRC patients (aOR 1.68, 95% CI 1.25 to 2.25). After adjusting for demographics, medical comorbidities, stage and site of CRC diagnosis, and prescription opioid use, people who used cannabis had significantly lower QoL than people who did not use cannabis (difference of -6.14, 95% CI -8.07 to -4.20). Conclusion: Among CRC survivors, cannabis use was common, associated with more advanced stages of disease, associated with tobacco and alcohol use, and not associated with better QoL. Clinicians should inquire about cannabis use among their patients and provide evidence-based recommendations for cancer-related symptoms.

Background & Aims Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. Methods Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) Results After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05–1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03–1.12; P = 3.3 × 10–4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06–1.18; P = 4.2 × 10–5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. Conclusions In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis., Graphical abstract

Background Higher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood. Methods We examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models. Results In sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relations. In multivariable MR analyses, associations of BMI and WHR with CRC were not attenuated following adjustment for representative metabolite classes, e.g., the univariable IVW OR for BMI with CRC was 1.12 (95% CI = 1.00, 1.26), and this became 1.11 (95% CI = 0.99, 1.26) when adjusting for cholesterol in low-density lipoprotein particles. Conclusions Our results suggest that higher BMI more greatly raises CRC risk among men, whereas higher WHR more greatly raises CRC risk among women. Adiposity was associated with numerous metabolic alterations, but none of these explained associations between adiposity and CRC. More detailed metabolomic measures are likely needed to clarify the mechanistic pathways.

BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.

Importance The US Preventive Services Task Force (USPSTF) released updated lung cancer screening recommendations in 2021, lowering the screening age from 55 to 50 years and smoking history from 30 to 20 pack-years. These changes are expected to expand screening access to women and racial and ethnic minority groups. Objective To estimate the population-level changes associated with the 2021 USPSTF expansion of lung cancer screening eligibility by sex, race and ethnicity, sociodemographic factors, and comorbidities in 5 community-based health care systems. Design, setting, and participants This cohort study analyzed data of patients who received care from any of 5 community-based health care systems (which are members of the Population-based Research to Optimize the Screening Process Lung Consortium, a collaboration that conducts research to better understand how to improve the cancer screening processes in community health care settings) from January 1, 2010, through September 30, 2019. Individuals who had complete smoking history and were engaged with the health care system for 12 or more continuous months were included. Those who had never smoked or who had unknown smoking history were excluded. Exposures Electronic health record-derived age, sex, race and ethnicity, socioeconomic status (SES), comorbidities, and smoking history. Main outcomes and measures Differences in the proportion of the newly eligible population by age, sex, race and ethnicity, Charlson Comorbidity Index, chronic obstructive pulmonary disease diagnosis, and SES as well as lung cancer diagnoses under the 2013 recommendations vs the expected cases under the 2021 recommendations were evaluated using χ2 tests. Results As of September 2019, there were 341 163 individuals aged 50 to 80 years who currently or previously smoked. Among these, 34 528 had electronic health record data that captured pack-year and quit-date information and were eligible for lung cancer screening according to the 2013 USPSTF recommendations. The 2021 USPSTF recommendations expanded screening eligibility to 18 533 individuals, representing a 53.7% increase. Compared with the 2013 cohort, the newly eligible 2021 population included 5833 individuals (31.5%) aged 50 to 54 years, a larger proportion of women (52.0% [n = 9631]), and more racial or ethnic minority groups. The relative increases in the proportion of newly eligible individuals were 60.6% for Asian, Native Hawaiian, or Pacific Islander; 67.4% for Hispanic; 69.7% for non-Hispanic Black; and 49.0% for non-Hispanic White groups. The relative increase for women was 13.8% higher than for men (61.2% vs 47.4%), and those with a lower comorbidity burden and lower SES had higher relative increases (eg, 68.7% for a Charlson Comorbidity Index score of 0; 61.1% for lowest SES). The 2021 recommendations were associated with an estimated 30% increase in incident lung cancer diagnoses compared with the 2013 recommendations. Conclusions and relevance This cohort study suggests that, in diverse health care systems, adopting the 2021 USPSTF recommendations will increase the number of women, racial and ethnic minority groups, and individuals with lower SES who are eligible for lung cancer screening, thus helping to minimize the barriers to screening access for individuals with high risk for lung cancer.

Colorectal cancer (CRC) is a leading cause of cancer death, yet many CRC deaths are preventable via CRC screening. Currently only age and family history are used to define screening eligibility. However, CRC risk varies substantially in the population. In recent years polygenic risk scores (PRS) have gained attention as powerful risk prediction tool to personalize interventions. PRS provides a quantitative measure of an individual's inherited risk based on the cumulative effect of many genetic risk variants. Here, we benchmark several genome wide PRS techniques to select the best performing models in CRC risk prediction. We built CRC risk prediction models that incorporate genome-wide genotype data from large-scale research studies (55,105 cases and 65,079 controls, European ancestries) with the imputed genetic data on over 40 million variants. The risk prediction models were externally evaluated in the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort, including 101,987 genotyped individuals within the Kaiser Permanente Northern California (KPNC) integrated healthcare delivery system. We built genome-wide PRS using various methods including known CRC risk variants, thresholding and pruning followed by machine learning approaches (ML), LDpred, improved LDpred2, SBayesR, PRS-CS, Lassosum and empirical Bayes. Among 55,033 individuals of European ancestry in the GERA cohort, we evaluated the performance of models in terms of the age and sex-adjusted AUC. We showed that LDpred, LDpred2, LDpred2-sparse, SBayesR and PRS-CS perform equally well in terms of discriminatory accuracy (AUC=0.65). In addition, the PRS developed using the above-mentioned techniques identified the top 30% of the GERA European population has a hazard ratio estimate of ~2.2 on CRC risk, which is comparable to that for having an affected first-degree relative. The developed CRC PRSs will provide way for risk-stratified CRC screening and other targeted interventions. PRS derivation methodsNo. of variantsAUC(1,311 cases and 53,722 controls)Hazard ratio estimates (CI)Top 30% of population vs. remainingKnown variants1400.631.92 (1.75-2.23)PT Clumping + ML (Ridge)10,0000.631.94 (1.72-2.19)LDpred1.2M0.652.20 (1.94-2.47)LDPred21.2M0.652.20 (1.93-2.45)LDpred2 Sparse530K0.652.20 (1.90-2.41)SBayesR1.2M0.652.20 (1.88-2.38)PRS-CS1.2M0.652.20 (1.91-2.43)Lassosum1.2M0.621.76 (1.56-2.58)EBPRS1.2M0.621.81 (1.66-2.11)AUC based on family history in GERA cohort is 0.54 Citation Format: Minta Thomas, Lori C Sakoda, Jeffrey K Lee, Mark A Jenkins, Andrea Burnett-Hartman, Heather Hampel, Elisabeth A Rosenthal, Hermann Brenner, Jenny Chang-Claude, Marc J Gunter, Polly A Newcomb, Steven Gallinger, Tabitha A Harrison, Graham Casey, Victor Moreno, Gail P Jarvik, Stephen B Gruber, Robert E Schoen, Andrew T Chan, Richard B Hayes, Douglas A Corley, Ulrike Peters, Li Hsu. Benchmarking genome-wide polygenic risk score development techniques in colorectal cancer risk prediction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 881.

Purpose Regular use of aspirin is associated with improved survival for patients with colorectal cancer (CRC). However, the timing of and the subtype of CRC that would benefit the most from using aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in relation to survival is unclear. Patients and Methods In all, 2,419 patients age 18 to 74 years with incident invasive CRC who were diagnosed from 1997 to 2008 were identified from population-based cancer registries in the United States, Canada, and Australia. Detailed epidemiologic questionnaires were administered at study enrollment and at 5-year follow-up. Survival outcomes were completed through linkage to national death registries. BRAF- and KRAS-mutation status, microsatellite instability, and CpG island methylator phenotype were also evaluated. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for overall survival (OS) and CRC-specific survival. Results After a median of 10.8 years of follow-up since diagnosis, 381 deaths (100 as a result of CRC) were observed. Compared with nonusers, postdiagnostic aspirin-only users had more favorable OS (HR, 0.75; 95% CI, 0.59 to 0.95) and CRC-specific survival (HR, 0.44; 95% CI, 0.25 to 0.71), especially among those who initiated aspirin use (OS: HR, 0.64; 95% CI, 0.47 to 0.86; CRC-specific survival: HR, 0.40; 95% CI, 0.20 to 0.80). The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status ( Pinteraction = .01). Use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60; 95% CI, 0.46 to 0.80) but not among those with KRAS-mutant tumors (HR, 1.24; 95% CI, 0.78 to 1.96). Conclusion Among long-term CRC survivors, regular use of NSAIDs after CRC diagnosis was significantly associated with improved survival in individuals with KRAS wild-type tumors.

Background As more states legalize cannabis for medical and recreational use, people increasingly use cannabis to treat medical conditions and associated symptoms. The prevalence and utility of cannabis for cancer-related symptoms may be clarified by examining cannabis use among patients with a common cancer diagnosis. We aimed to determine the prevalence of cannabis use among colorectal cancer (CRC) survivors and its associations with quality of life (QoL) and cancer-related symptomatology. Methods A cross-sectional survey of patient-reported QoL outcomes and behaviors, including cannabis use, was conducted within the Patient Outcomes To Advance Learning network’s (PORTAL) CRC Cohort. The cohort included a population-based sample of healthcare system members ≥18 years old diagnosed with adenocarcinoma of the colon or rectum from 2010 through 2016. We assessed the association between cannabis use and QoL using the European Organization for Research and Treatment of Cancer QLQ-C30 summary score. Results Of the 1784 respondents, 293 (16.4%) reported cannabis use following CRC diagnosis. Current tobacco smokers were more likely to use cannabis compared to former or never tobacco smokers (adjusted odds ratio [aOR] 2.71, 95% confidence interval [CI] 1.56 to 4.70). Greater alcohol use (> 4 drinks per month versus ≤4 drinks per month) was associated with cannabis use (aOR 2.17, 95% CI 1.65 to 2.85). There was an association between cannabis use and cancer stage at diagnosis, with stage 3 or 4 CRC patients more likely to use cannabis than stage 1 or 2 CRC patients (aOR 1.68, 95% CI 1.25 to 2.25). After adjusting for demographics, medical comorbidities, stage and site of CRC diagnosis, and prescription opioid use, people who used cannabis had significantly lower QoL than people who did not use cannabis (difference of − 6.14, 95% CI − 8.07 to − 4.20). Conclusion Among CRC survivors, cannabis use was relatively common, associated with more advanced stages of disease, associated with tobacco and alcohol use, and not associated with better QoL. Clinicians should inquire about cannabis use among their patients and provide evidence-based recommendations for cancer-related symptoms.

PURPOSE To evaluate health care systems for the availability of population-level data on the frequency of use and results of clinical molecular marker tests to inform precision cancer care. METHODS We assessed cancer-related molecular marker test data availability across 12 US health care systems in the Cancer Research Network. Overall, these systems provide care to a diverse population of more than 12 million people in the United States. We performed qualitative analyses of test data availability for five blood-based protein, nine germline, and 14 tissue-based tumor marker tests in each health care system’s electronic health record and tumor registry using key informants, test code lists, and manual review of data types and output. We then performed quantitative analyses to estimate the proportion of patients with cancer with test utilization data and results for specific molecular marker tests. RESULTS Health systems were able to systematically capture population-level data on all five blood protein markers, six of 14 tissue-based tumor markers, and none of the nine germline markers. Successful, systematic data capture was achievable for tests with electronic data feeds for test results (blood protein markers) or through prior manual abstraction by tumor registrars (select tumor-based markers). For test results stored in scanned image files (particularly germline and tumor marker tests), information on which test was performed and test results was not readily accessible in an electronic format. CONCLUSION Even in health care systems with sophisticated electronic health records, there were few codified data elements available for evaluating precision cancer medicine test use and results at the population level. Health care organizations should establish standards for electronic reporting of precision medicine tests to expedite cancer research and facilitate the implementation of precision medicine approaches.

PURPOSE: To describe patterns of opioid use in cancer survivors. METHODS: In a cohort study of colon cancer patients diagnosed during 1995–2014 and enrolled at two Kaiser Permanente regions, we constructed quarterly measures of opioid use from one year before cancer diagnosis through five years after diagnosis to examine changes in use. Measures included any use, incident use, regular use (use ≥ 45 days in a 91-day quarter), and average daily dose (converted to morphine milligram equivalent, MME). We also assessed temporal trends of opioid use. RESULTS: Of 2,039 colon cancer patients, 11–15% received opioids in the four pre-diagnosis quarters, 68% in the first quarter after diagnosis, and 15–17% in each subsequent 19 quarters. Regular opioid use increased from 3–5% pre-diagnosis to 5–7% post diagnosis. Average dose increased from 15–17 MME/day pre-diagnosis to 14–22 MME/day post diagnosis (excluding the quarter in which cancer was diagnosed). Among post-diagnosis opioid users, 73–95% were on a low dose (< 20 MME/day). Over years, regular use of opioids increased in survivorship with no change in dosage. CONCLUSION: Opioid use slightly increased following a colon cancer diagnosis, but high-dose use was rare. Research is needed to differentiate under- vs. over- treatment of cancer pain.

PURPOSE: Colorectal cancer (CRC) screening guidelines recommend increased surveillance of individuals with sessile serrated adenomas/polyps (SSA/Ps), but there is uncertainty about the risk associated with SSA/Ps. We aimed to determine the association between SSA/Ps and subsequent advanced colorectal neoplasia. METHODS: This case-control study included Kaiser Permanente Washington (KPWA) members who received an index colonoscopy between 1/1/1998 and 12/31/2007, and had hyperplastic polyps (HPs) or SSA/Ps but no conventional adenomas according to study pathologist histologic review. Subsequent pathology reports and biopsies through 1/1/2013 were reviewed for advanced colorectal neoplasia. We linked to the Seattle-Puget Sound Surveillance Epidemiology and End Results (SEER) registry to identify additional CRC cases. We used generalized estimating equations with a logit link to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for advanced colorectal neoplasia, comparing those with SSA/Ps to those with HPs. RESULTS: There were 161 individuals with index SSA/Ps, 548 with HPs, and 918 subsequent endoscopies included in analyses. Of those with index SSA/Ps, 19 had subsequent advanced colorectal neoplasia; 39 with HPs had subsequent advanced colorectal neoplasia. Compared to those with HPs, those with SSA/Ps were not statistically significantly more likely to have subsequent advanced colorectal neoplasia (adjusted OR 1.79; CI 0.98–3.28). Polyp size ≥ 10 mm, right colon location, and the presence of multiple serrated polyps were also not associated with advanced colorectal neoplasia. CONCLUSIONS: Our results suggest that there is not a strong association between SSA/Ps and subsequent advanced colorectal neoplasia during the 5 years following SSA/P removal.

Our objective was to describe differences in treatment patterns and survival between early-onset ( 50 years old) and late-onset colorectal cancer (CRC) patients in community-based health systems.We used tumor registry and electronic health record data to identify and characterize patients diagnosed with adenocarcinoma of the colon or rectum from 2010 to 2014 at six US health systems in the patient outcomes to advance learning (PORTAL) network. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the distribution of tumor characteristics and treatment patterns in early-onset versus late-onset CRC. Cox regression models were used to estimate adjusted hazard ratios (HRs) and CIs comparing survival between early- and late-onset CRC patients.There were 1,424 early-onset and 10,810 late-onset CRC cases in our analyses. Compared to late-onset CRC, early-onset CRC was significantly associated with advanced-stage disease, high-grade histology, signet ring histology, and rectal or left colon location. After adjusting for differences in tumor and patient characteristics, early-onset patients were more likely than late-onset patients to have 12 lymph nodes examined (OR 1.60, CI 1.37-1.87), to receive systemic therapy (chemotherapy or immunotherapy) within 6 months of diagnosis (OR 2.84, CI 2.40-3.37), and to have a reduced risk of CRC-specific death (HR 0.66, CI 0.56-0.79).Early-onset CRC is associated with aggressive tumor characteristics, distal location, and systemic therapy use. Despite some adverse risk factors, these patients tend to have better survival than older onset patients.

Introduction Understanding sleep quality among colorectal cancer (CRC) patients could contribute to improved survivorship care in terms of sleep recommendations. Methods We ascertained sleep quality within an ongoing population-based study of CRC patients identified through the Puget Sound SEER cancer registry. We assessed sleep quality using components of the standardized Pittsburg Sleep Quality Index. Differences in sleep quality by CRC site were analyzed using chi-square and ANOVA tests. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of tumor site (rectal vs. colon) with sleep quality concerns. ORs were adjusted for age at diagnosis, sex, BMI, education, cancer stage, and time since diagnosis. Results Of the 1,454 CRC patients included in analyses, 37% (N=543) had rectal cancer compared to 63% (N=911) with colon cancer, and the stage distribution was as follows: 37% localized, 43% regional, and 18% distant stage. Overall, participants with rectal (vs. colon) cancer were more likely to report problems related to trouble sleeping (OR [CI]: 1.63 [1.23, 2.16]), but were also less likely to report trouble sleeping specifically due to issues with breathing, coughing, or snoring (OR [CI]: 0.51 [0.27, 0.96]. However, rectal cancer patients were more likely than colon cancer patients to report changes in sleep patterns after cancer diagnosis (OR [CI]: 1.33 [1.02, 1.73]), and to report trouble sleeping specifically due to getting up to use the bathroom (OR [CI]: 1.49 [1.17, 1.90]) or pain (OR [CI]: 1.50 [1.10, 2.04]). There were no significant differences between rectal and colon cancer cases in terms of amount of sleep, problems staying awake, bad sleep quality, and use of sleep medication. Conclusion Overall, rectal cancer patients are more likely to have sleep complications due to potential physical consequences compared to colon cancer patients. This suggests that survivorship care may be adapted according to CRC site to ensure patients receive appropriate support in terms of sleep recommendation. Support (if any)

Introduction Nationally, a greater proportion of American Indians and Alaska Natives (AI/ANs) are diagnosed with advanced-stage cancers compared with non-Hispanic whites. The reasons for observed differences in stage at diagnosis between AI/ANs and non-Hispanic whites remain unclear. Methods Medicaid, Indian Health Service Care Systems, and state cancer registry data for California, Oregon, and Washington (2001–2008, analyzed in 2014–2015) were linked to identify AI/ANs and non-Hispanic whites diagnosed with invasive breast, cervical, colorectal, lung, or prostate cancer. Logistic regression was used to estimate ORs and 95% CIs for distant disease versus local or regional disease, in AI/ANs compared with non-Hispanic white case patients. Results A similar proportion of AI/AN (31.2%) and non-Hispanic white (35.5%) patients were diagnosed with distant-stage cancer in this population (AOR=1.03, 95% CI=0.88, 1.20). No significant differences in stage at diagnosis were found for any individual cancer site. Among AI/ANs, Indian Health Service Care Systems eligibility was not associated with stage at diagnosis. Conclusions In contrast to the general population of the U.S., among Medicaid enrollees, AI/AN race is not associated with later stage at diagnosis. Cancer survival disparities associated with AI/AN race that have been observed in the broader population may be driven by factors associated with income and health insurance that are also associated with race, as income and insurance status are more homogenous within the Medicaid population than within the broader population.

Kaiser Permanente (KP) is an ideal environment to study the spectrum of cancer prevention and control because it provides comprehensive cancer care to a large and diverse community. The Kaiser Permanente Research Bank (KPRB) is collecting biospecimens and a survey of health-related behaviors and other risk factors from about 400,000 adults aged 18 years and older across all eight KP regions. The KPRB includes a cancer cohort and cases are identified from KP region-specific algorithms designed to identify cancer cases within days of diagnosis, and from linkage with regional tumor registries. KPRB participation involves completing an online informed consent and survey, and providing a blood or saliva sample. KPRB participants consent to linkage to their electronic health record (EHR), which includes comprehensive information about cancer screening, diagnosis and treatment. A key strength of this cohort is its diversity with respect to age, race/ethnicity, and geographic location (Hawai’i, Oregon, Washington state, California, Colorado, Georgia, and the Washington, DC area). To date, the KPRB includes 68,000 cancer cases, 56% are women, and 30% are non-white. Over 8,500 cases were diagnosed before the age of 50 and the cohort includes substantial numbers of cancer cases among Asian and Pacific Islanders (n=8,941), Hispanics (n=7,678), and non-Hispanic blacks (n=5,367). Although all cohort members have insurance, and thus, presumably access to care, we observed disparities in stage at diagnosis. Compared to non- Hispanic whites, non-Hispanic Blacks are more likely to be diagnosed at stage 4 (5% versus 16%, respectively, of all cases); participants describing themselves as multi- racial or “other” race similarly have a very high proportion (25%) of cases diagnosed at stage 4. Research is planned to examine the factors associated with this disparity. The extensive EHR, access to stored tissue specimens, detailed treatment data, and ability to follow patients over time for recurrence and mortality make the KPRB Cancer Cohort an exceptional resource for exploring the factors that contribute to cancer etiology, progression, and survival. We invite investigators to apply to use the KPRB (https://researchbank.kaiserpermanente.org/) to accelerate progress toward improving cancer care. Citation Format: Heather S. Feigelson, Christina Clarke, Andrea Burnett- Hartman, Stephen Van Den Eeden, Sheila Weinmann, Monica Ter-Minassian, Stacey Honda, Deborah Young, Aruna Kamineni, Sarah Rowell, Alan Bauck, Elizabeth McGlynn. The Kaiser Permanente Research Bank cancer cohort: A diverse resource to improve cancer care [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-178.

Purpose: Despite declines in the overall incidence and mortality of colorectal cancer (CRC), there have been increases in the incidence and mortality of CRC among those < 50 years old (early-onset CRC). Although the reasons for the increases in early-onset CRC are unknown, one hypothesis is that temporal changes in dietary patterns has led to changes in the consumption of foods that are associated with increased CRC risk, in particular red and processed meats. Thus, the purpose of our analyses was to evaluate differences in dietary factors between early-onset and late-onset CRC patients. Methods: We used the Puget Sound SEER cancer registry to identify a population-based sample of patients diagnosed with CRC from 4/1/2016 through 12/31/2018. CRC patients were recruited to the study via mail and telephone, and consented patients completed a questionnaire assessing patient demographics, medical history, and CRC risk factors, including diet. For dietary factors, we ascertained information on the average number of servings per week of fruits, vegetables, red meat, processed meat, and “spicy” foods two years prior to CRC diagnosis. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing dietary intake in early-onset vs. late-onset CRC. ORs were adjusted for sex, race/ethnicity, cigarette smoking history, diabetes, hyperlipidemia, and alcohol consumption. Results: There were 304 early-onset and 1,150 late-onset CRC patients in our analyses. Compared to late-onset patients, those with early-onset CRC were less likely to be current smokers or to have a history of diabetes or hyperlipidemia. After adjustment for these differences, compared to late-onset CRC, early-onset CRC patients had higher intake of red meat (OR for quartile 4 vs. quartile 1 = 1.49 CI: 1.02 - 2.17), processed meat (OR for quartile 4 vs. quartile 1 = 1.63 CI: 1.16 -2 .29), and spicy food (OR for quartile 4 vs. quartile 1 = 1.80 CI: 1.25 - 2.58). However, there was not a statistically significant difference between early- and late-onset CRC patients with regard to fruit (OR for quartile 4 vs. quartile 1 = 1.07 CI: 0.73 - 1.57) or vegetable (OR for quartile 4 vs. quartile 1 = 0.87 CI: 0.62 - 1.22) consumption. Conclusion: Our results suggest that dietary patterns differ between early- and late-onset CRC patients; in particular, early-onset CRC patients had higher intake of red meat, processed meat, and spicy food. This may reflect differences is dietary patterns by age; additional research with population-based controls is needed to determine the association between diet and early-onset colorectal cancer. Citation Format: Andrea N. Burnett-Hartman, Mimi (Trucmai) Ton, Chad (Qianchuan) He, Rachel C. Malen, Amanda I. Phipps, Julia D. Labadie, Heather Spencer Feigelson, Polly A. Newcomb. A comparison of dietary factors between early-onset and late-onset colorectal cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-161.

PURPOSE: To describe the association between diabetes and colon cancer recurrence. METHODS: We conducted a cohort study at two integrated health care delivery systems in the United States. Using tumor registry data, we identified patients aged ≥18 years when diagnosed with stage I–IIIA adenocarcinomas of the colon during 1995‒2014. Pre-existing diabetes was ascertained via diagnosis codes. Medical records were reviewed for eligibility and to abstract recurrence and covariate information. Recurrence was ascertained beginning 90 days after the end of colon cancer treatment (i.e., cohort entry). Recurrence of any cancer or a new primary cancer at any site was a secondary outcome. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for the associations between diabetes at cohort entry and study outcomes. RESULTS: Among the 1,923 eligible patients, 393 (16.7%) had diabetes at cohort entry. Diabetes was not associated with recurrence (HR = 0.87; 95% CI: 0.56–1.33) or with any subsequent cancer (HR = 1.09; 95% CI: 0.85–1.40). When the definition of recurrence included second primary colorectal cancer, risk was non-significantly higher in patients with diabetes than without diabetes. CONCLUSIONS: The risk of colon cancer recurrence appears to be similar in patients with and without diabetes at diagnosis. IMPACT: Future studies should evaluate the association between diabetes and colorectal cancer outcomes, especially second primary colon cancers, in larger populations.

Background Short telomeres have been associated with increased risk of many cancers, particularly cancers of the gastrointestinal tract including esophagus and stomach. However, the association between telomere length (TL) and colorectal cancer and its precursors, colorectal polyps, is not clear. Methods We investigated the relationship between TL and risk of colorectal polyp subtypes in a colonoscopy-based study in western Washington. Participants were 35–79 year-old enrollees at an integrated health care system, who underwent a colonoscopy between 1998 and 2007 (n = 190), completed a self-administered questionnaire, provided blood samples, and were distinguished as having adenomas, serrated polyps, or as polyp-free controls through a standardized pathology review. Telomere length (T) relative to a single copy gene (S) was measured in circulating leukocytes from stored buffy coat samples using quantitative polymerase chain reaction. Multivariable polytomous logistic regression was used to compare case groups with polyp-free controls and other case groups; adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Results TL in the shortest tertile (T/S ratio

Purpose. We aimed to determine whether the association between late-stage cancer and American Indian/Alaska Native (AI/AN) race differed by enrollment in the Indian Health Service Care System (IHSCS). Methods. We used Surveillance, Epidemiology, and End Results (SEER) data linked to Medicare files to compare the odds of late-stage breast, colorectal, lung, or prostate cancer between non-Hispanic Whites (NHWs) (n=285,993) and AI/ANs with (n=581) and without (n=543) IHSCS enrollment. Results. For AI/ANs without IHSCS enrollment, the odds of late-stage disease were higher in AI/ANs compared with NHWs for breast (OR=3.17, 95%CI: 1.82–5.53) and for prostate (OR=2.59, 95%CI:1.55–4.32) cancer, but not for colorectal or lung cancers. Among AI/ANs with IHSCS enrollment, there was not a significant association between late-stage disease and AI/AN race for any of the four cancers evaluated. Conclusion. Our results suggest that enrollment in the IHSCS reduced the disparity between AI/ANs and NHWs with respect to late-stage cancer diagnoses.

Background: Little has been reported regarding patterns of oncologic care in American Indian/Alaska Natives (AI/AN). Observed worse survival has been attributed to later-stage presentation. We aimed to evaluate racial differences in cancer-directed therapy and hospice care utilization in AI/ANs and non-Hispanic whites (NHW) with metastatic cancer. Methods: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare claims database was accessed for AI/AN and NHW metastatic-cancer cases diagnosed between 2001 and 2007. Utilization of cancer-directed therapy (surgery, radiation, and/or chemotherapy) and/or hospice services was compared between AI/ANs and NHWs. Minimally adjusted (age, sex, diagnosis year) and fully-adjusted (also Klabunde comorbidity score, sociodemographic factors) regression models were used to estimate odds (OR) and hazard ratios (HR) for receipt of care. Results: AI/ANs were younger, more likely to reside in the West, be unmarried, have lower income, and live in a nonurban setting than NHWs. Fewer AI/ANs received any cancer-directed therapy (57% vs. 61% NHWs) within 3 months of diagnosis; sociodemographic factors accounted for much of this difference [fully-adjusted HR, 0.94; 95% confidence interval (CI), 0.83–1.08]. We noted differences in hospice utilization between AI/ANs (52%) and NHWs (61%). A significant difference in hospice utilization remained after adjustment for sociodemographics (OR, 0.78; 95% CI, 0.61–0.99). Conclusion: Observed absolute differences in care for AI/ANs and NHWs with metastatic cancer were largely accounted for by adjusting for socioeconomics, comorbidities, and demographic factors. A significant association between race and hospice utilization was noted. Impact: Efforts to improve metastatic-cancer care should focus on socioeconomic barriers and investigate the observed disparity in receipt of hospice services. Cancer Epidemiol Biomarkers Prev; 24(7); 1138–43. ©2015 AACR.

To assess whether timing of initial post-diagnosis cancer care differs between American Indian and Alaska Native (AI/AN) and non-Hispanic White (NHW) patients, we accessed SEER-Medicare data for breast, colorectal, lung, and prostate cancers (2001-2007). Medicare claims data were examined for initiation of cancer-directed treatment. Overall, AI/ANs experienced longer median times to starting treatment than NHWs (45 and 39 days, plt; .001) and lower rates of treatment initiation (HR[95%CI]: 0.86[0.79-0.93]). Differences were largest for prostate (HR: 0.80[0.71-0.89]) and smallest for breast cancer (HR: 0.96[0.83-1.11]). American Indians / Alaska Natives also had elevated odds of greater than 10 weeks between diagnosis and treatment compared with NHWs (OR[95% CI]: 1.37[1.16-1.63]), especially for prostate cancer (OR: 1.41[1.14-1.76]). Adjustment for comorbidity and socio-demographic factors attenuated associations except for prostate cancer. In this insured population, we observed evidence that AI/ANs start cancer therapy later than NHWs. The modest magnitude of delays suggests that they are unlikely to be a determinant of survival disparities.

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.

Sex steroid hormones play a role in colorectal cancer (CRC) development, but little is known about their influence on tumor progression and metastasis. Because catechol-O-methyltransferase (COMT; 22q11.21) activity is an important component of estrogen-mediated carcinogenesis, we hypothesized that germline variation in COMT may be associated with CRC survival.We identified 10 single nucleotide polymorphisms that tagged variation across two isoforms of COMT in 2,458 women with CRC from the Nurses' Health Study, Postmenopausal Hormones Supplementary Study to the Colon Cancer Family Registry, VITamins And Lifestyle Study, and Women's Health Initiative. All four studies participated in the Genetics and Epidemiology of Colorectal Cancer Consortium.During a median follow-up of 7 years across all studies, there were 799 deaths, including 566 deaths from CRC. Based on multiple comparisons, no associations between single nucleotide polymorphisms and CRC-specific or overall survival reached statistical significance, including the well-characterized Val108/158Met polymorphism (rs4680; CRC-specific survival: hazard ratio per minor allele, 1.04; 95% CI, 0.92-1.17; overall survival: hazard ratio per minor allele, 1.01; 95% CI, 0.90-1.14).In this large study of women with CRC, we find no evidence that common inherited variation in COMT is associated with survival time after diagnosis.

Relatively little is known about factors associated with long-term survival (LTS) following a diagnosis of ovarian cancer. We conducted a retrospective observational study of high-grade serous ovarian cancer (HGSOC) to explore predictors of LTS, defined as >= 7 years of survivorship, using data from five participating health plans in the Cancer Research Network (CRN, http:\\crn.cancer.gov). Our primary data source was the Virtual Data Warehouse (VDW), a common data model which includes standardized, individual-level data extracted from the electronic data systems of each study site. We included 642 women with incident HGSOC diagnosed between 2000 and 2008 to allow for at least 7 years of follow-up. We conducted a multivariable logistic regression analysis to compare characteristics of women who survived >=7 years after diagnosis (n=148) to those who died within 7 years of diagnosis (n=494). In addition to stage and grade, predictors considered for the model included age, race, smoking status at time of diagnosis, body mass index (BMI) within the year prior to diagnosis, and CA-125 level prior to cancer treatment. We examined estrogen and hormonal contraceptive use, as well as the prevalence of comorbidities in the year prior to diagnosis of ovarian cancer. We also included variables for receipt of surgery, radiation, and chemotherapy. We used forward selection to include variables, and retained them in the final model if they had a p-value of =35 units/ml), Charlson comorbidity score, receipt of chemotherapy, BMI, and five separate comorbid conditions: weight loss, hypothyroidism, liver disease, chronic pulmonary disease and hypertension. Of these, only younger age, lower stage, and receipt of chemotherapy were statistically significantly associated with LTS. The OR for LTS was 2.9 (95% CI: 1.2-6.3) for ages 18-49 years at diagnosis compared to >=70 years of age. Those who were diagnosed at stage IV had statistically significantly lower odds of surviving >=7 years than any other stage of disease. The OR for LTS for stage I vs. stage IV was 46.6 (95% CI: 46.7 – 15.9), stage II vs. stage IV was 14.1 (95% CI: 5.3-37.0) and stage III vs. stage IV was 5.3 (95% CI: 2.7-10.4). The OR was 2.9 (95% CI: 1.0-8.4) for receipt of chemotherapy versus no chemotherapy after adjusting for all other covariates. Our analysis of data from electronic medical records did not identify any new characteristics that may be associated with ovarian cancer LTS. Citation Format: Christina L. Clarke, Lawrence H. Kushi, Jessica Chubak, Pamala A. Pawloski, Joanna E. Bulkley, Mara M. Epstein, Andrea N. Burnett-Hartman, Bethan Powell, C. Leigh Pearce, Heather Spencer Feigelson. DESCRIBING THE ODDS OF LONG-TERM SURVIVAL AMONG WOMEN DIAGNOSED WITH HIGH-GRADE SEROUS OVARIAN CANCER USING ELECTRONIC MEDICAL RECORDS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-004.

Background and aimsPrior studies suggest that colonoscopy may exacerbate inflammatory bowel disease (IBD) symptoms. Thus, our study aimed to determine risk of emergency room (ER) visits associated with colonoscopy among IBD patients and evaluate potential modifiers of this risk.MethodsThe study population included IBD patients in the Multi-Payer Claims Database who were >20 years old and had a colonoscopy from 2007-2010. We used a self-controlled risk interval design and mixed-effects Poisson regression models to calculate risk ratios (RR) and 95% confidence intervals (CI) comparing the incidence of ER visits in the 1-4 weeks following colonoscopy (risk interval) to the incidence of ER visits in the 7-10 weeks after colonoscopy (control interval). We also conducted stratified analyses by patient characteristics, bowel preparation type, and medication.ResultsThere were 212,205 IBD patients with at least 1 colonoscopy from 2007-2010, and 3,699 had an ER visit during the risk and/or control interval. The risk of an ER visit was higher in the 4-week risk interval following colonoscopy compared to the control interval (RR = 1.24; 95% CI: 1.17-1.32). The effect was strongest in those ConclusionsOur results suggest that there is an increased risk of ER visits following colonoscopy among IBD patients, but that immunomodulators and mild bowel preparation agents may mitigate this risk.

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.

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. 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. 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. Our results suggest that reproductive factors, including OC use, are not associated with early colorectal cancer precursor lesions.

Background: To reduce colorectal cancer mortality, positive fecal blood tests must be followed by colonoscopy. Methods: We identified 62,384 individuals ages 50 to 89 years with a positive fecal blood test between January 1, 2011 and December 31, 2012 in four health care systems within the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We estimated the probability of follow-up colonoscopy and 95% confidence intervals (CI) using the Kaplan–Meier method. Overall differences in cumulative incidence of follow-up across health care systems were assessed with the log-rank test. HRs and 95% CIs were estimated from multivariate Cox proportional hazards models. Results: Most patients who received a colonoscopy did so within 6 months of their positive fecal blood test, although follow-up rates varied across health care systems (P Conclusion: Individual characteristics and health care system were associated with colonoscopy after positive fecal blood tests. Patterns were consistent across health care systems, but proportions of patients receiving follow-up varied. These findings suggest that there is room to improve follow-up of positive colorectal cancer screening tests. Impact: Understanding the timing of colonoscopy after positive fecal blood tests and characteristics associated with lack of follow-up may inform future efforts to improve follow-up. Cancer Epidemiol Biomarkers Prev; 25(2); 344–50. ©2016 AACR.

Background:BRAF mutations in colorectal cancer (CRC) are disproportionately observed in tumors exhibiting microsatellite instability (MSI) and are associated with other prognostic factors. The independent association between BRAF mutation status and CRC survival, however, remains unclear. Methods: We evaluated the association between the BRAF c.1799T>A (p.V600E) mutation and survival in individuals with incident invasive CRC diagnosed between 1997 and 2007 in Western Washington State. Tumor specimens were tested for this BRAF mutation and MSI status. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the association between BRAF mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumor site, stage, and MSI status. Results: Among 1,980 cases tested, 12% were BRAF c.1799T>A (p.V600E) mutation–positive (n = 247). BRAF-mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05–1.95). This association was limited to cases diagnosed at ages Conclusions: Our results show that the prevalence of BRAF mutations in CRC differs by patient and tumor characteristics and suggest that the association between BRAF status and CRC survival may differ by some of these factors. Impact: The presence of a BRAF c.1799T>A (p.V600E) mutation is associated with significantly poorer prognosis after CRC diagnosis among subgroups of patients. Cancer Epidemiol Biomarkers Prev; 21(10); 1792–8. ©2012 AACR.

566 Background: While overall incidence and mortality of colorectal cancer (CRC) has declined, incidence and mortality are increasing in those < 50 years old (early-onset CRC). Our objective was to better understand early-onset CRC by comparing tumor characteristics and initial treatment type between early-onset and normal/late-onset CRC. Methods: We used health system and national tumor registries to identify patients diagnosed with adenocarcinoma of the colon or rectum from 2010-2014 at 6 US integrated health systems in the Patient Outcomes To Advance Learning (PORTAL) network. Tumor registry data included: age at diagnosis, stage, grade, anatomic site, histology, number of lymph nodes examined, and receipt of initial systemic therapy (chemotherapy or immunotherapy). Demographics and other patient characteristics were obtained from the EHR. We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the distribution of tumor characteristics and treatment patterns in early-onset ( < 50 years old) vs. normal/late-onset CRC. Results: There were 1,424 early-onset and 10,810 normal/late onset CRC cases in our analyses. Compared to normal/late onset cases, patients with early-onset CRC were more likely to be Hispanic, obese, never smokers, and to have Charlson comorbidity scores < 3. After adjustment for patient characteristics, compared to normal/late onset CRC, early-onset CRC was associated with more advanced stage disease (OR for stage 4 vs. stage 1 = 2.8, CI: 2.4-3.4), high grade histology (OR for poorly differentiated/undifferentiated vs. well/moderately differentiated = 1.2, CI: 1.1-1.5), signet ring histology (OR for signet ring vs. non-mucinous adenocarcinoma = 1.7, CI: 1.1, 2.6), and rectal (OR for rectum vs. cecum = 2.4, CI: 1.9-2.9) or left colon location (OR for left colon vs. cecum = 2.2, CI: 1.8-2.8). After adjustment for patient and tumor characteristics, early-onset patients were more likely than normal/late onset patients to have > 12 lymph nodes examined (OR = 1.6, CI: 1.4-1.8) and to receive systemic therapy (OR = 2.8, CI: 2.4, 3.4). Conclusions: Early-onset CRC is associated with aggressive tumor characteristics, distal location, and systemic therapy use.

ObjectiveMultivitamin supplements are used by nearly half of middle-aged women in the USA. Despite this high prevalence of multivitamin use, little is known about the effects of multivitamins on health outcomes, including cancer risk. Our main objective was to determine the association between multivitamin use and the risk of breast cancer in women.DesignWe conducted a population-based case–control study among 2968 incident breast cancer cases (aged 20–69 years), diagnosed between 2004 and 2007, and 2982 control women from Wisconsin, USA. All participants completed a structured telephone interview which ascertained supplement use prior to diagnosis, demographics and risk factor information. Odds ratios and 95 % confidence intervals were calculated using multivariable logistic regression.ResultsCompared with never users of multivitamins, the OR for breast cancer was 1·02 (95 % CI 0·87, 1·19) for current users and 0·99 (95 % CI 0·74, 1·33) for former users. Further, neither duration of use (for ≥10 years: OR = 1·13, 95 % CI 0·93, 1·38,Pfor trend = 0·25) nor frequency (>7 times/week: OR = 1·00, 95 % CI 0·77, 1·28,Pfor trend = 0·97) was related to risk in current users. Stratification by menopausal status, family history of breast cancer, age, alcohol, tumour staging and postmenopausal hormone use did not significantly modify the association between multivitamin use and breast cancer.ConclusionsThe current study found no association between multivitamin supplement use and breast cancer risk in women.

Background and Aims Colorectal cancer (CRC) is a heterogeneous disease that can develop via several pathways. Different CRC subtypes, identified based on tumor markers, have been proposed to reflect these pathways. We evaluated the significance of these previously proposed classifications to survival. Methods Participants in the population-based Seattle Colon Cancer Family Registry were diagnosed with invasive CRC from 1998 through 2007 in western Washington State (N = 2706), and followed for survival through 2012. Tumor samples were collected from 2050 participants and classified into 5 subtypes based on combinations of tumor markers: type 1 (microsatellite instability [MSI]–high, CpG island methylator phenotype [CIMP] –positive, positive for BRAF mutation, negative for KRAS mutation); type 2 (microsatellite stable [MSS] or MSI-low, CIMP-positive, positive for BRAF mutation, negative for KRAS mutation); type 3 (MSS or MSI low, non-CIMP, negative for BRAF mutation, positive for KRAS mutation); type 4 (MSS or MSI-low, non-CIMP, negative for mutations in BRAF and KRAS ); and type 5 (MSI-high, non-CIMP, negative for mutations in BRAF and KRAS ). Multiple imputation was used to impute tumor markers for those missing data on 1–3 markers. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of subtypes with disease-specific and overall mortality, adjusting for age, sex, body mass, diagnosis year, and smoking history. Results Compared with participants with type 4 tumors (the most predominant), participants with type 2 tumors had the highest disease-specific mortality (HR = 2.20, 95% CI: 1.47–3.31); subjects with type 3 tumors also had higher disease-specific mortality (HR = 1.32, 95% CI: 1.07–1.63). Subjects with type 5 tumors had the lowest disease-specific mortality (HR = 0.30, 95% CI: 0.14–0.66). Associations with overall mortality were similar to those with disease-specific mortality. Conclusions Based on a large, population-based study, CRC subtypes, defined by proposed etiologic pathways, are associated with marked differences in survival. These findings indicate the clinical importance of studies into the molecular heterogeneity of CRC.

Background: Persistent infection with oncogenic human papillomavirus (HPV) types-16 and -18 is an established cause of cervical and other cancers. Some studies report detection of oncogenic HPV DNA in colorectal carcinomas, with prevalence estimates as high as 84%. However, other studies report detecting no HPV DNA in colorectal tumors. Methods: To evaluate the prevalence of HPV in colorectal cancer subsets, we conducted a case–case comparison study. This study included 555 cases of incident colorectal cancer from the Seattle Colon Cancer Family Registry (CCFR), ages 20 to 74 years and diagnosed between 1998 and 2002. Standardized interviews were used to elicit demographics and risk factor data. Tumor DNA was assayed for HPV-16 and -18 DNA using real-time PCR. Microsatellite instability (MSI) status was assessed using a standard 10-marker panel and confirmed with immunohistochemical staining. Prevalence estimates were calculated for the overall sample, and stratified by patient and tumor characteristics. Fisher exact test was used to compare prevalence between strata. Results: HPV-16 DNA was detected in 2% of colorectal tumors, but no HPV-18 DNA was detected. HPV-16 prevalence did not vary between cases according to sex, age, race, smoking-status, or MSI-status (P > 0.05). HPV-16 prevalence in rectal carcinomas was 5% compared with 1% in colon carcinomas (P = 0.03). Conclusions: Among a large sample of colorectal carcinomas, prevalence of HPV-16 and -18 was very low. Prior studies detecting high HPV prevalence in colorectal carcinomas are likely the result of contamination from the anal canal or clinical processing. Impact: HPV is unlikely to play a large role in colorectal carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(2); 317–9. ©2012 AACR.

Background: Type-2 diabetes mellitus (T2DM) and colorectal cancer (CRC) are both relatively common diseases among the adult population in the US; both diseases also share similar risk factors, including obesity, chronic inflammation, sedentary lifestyle, and selected dietary factors. Estimates suggest that 14% of CRC patients have T2DM as a comorbid condition at diagnosis. T2DM has also been identified as an independent risk factor for colorectal cancer. Most colorectal cancers arise from polyp precursor lesions, including advanced adenomas and a subset of serrated polyps, termed sessile serrated polyps. There is limited evidence regarding the association between T2DM and specific subtypes of colorectal polyps. We investigated the relationship between T2DM and the risk of subsets of colorectal polyps in a colonoscopy-based study in western Washington State. Methods: Study participants were a subset of 20-79 year-old enrollees at Group Health, a population-based integrated health care system in the greater Puget Sound area in Washington State, who underwent a colonoscopy for any indication from 1998-2007. Eligible study participants completed a structured questionnaire to collect risk factor information, including self-report of clinically-diagnosed diabetes, and whether it was treated with medications. Participants were diagnosed as having adenomas (n=633), serrated polyps (n=602), synchronous presence of both adenomas and serrated polyps (n= 244) or as polyp-free controls (n=1052) on the basis of a standardized pathology review. Multivariable polytomous logistic regression was used to compare case groups with polyp-free controls and other case groups. Odds ratios (OR) and 95% confidence intervals (CI) were estimated, overall and by subtype, adjusted for age, sex, race, educational status, body mass index, smoking, alcohol intake, aspirin and nonsteroidal anti-inflammatory drug use, physical activity, history of previous endoscopy, and diet (fruits, vegetables and red meat intake). Results: About 10% of the study population reported a history of clinically diagnosed T2DM, and 77% of those with T2DM took anti-diabetic medications. T2DM was not associated with the risk for colorectal polyps overall (adjusted OR 0.84; 95% CI 0.61-1.15). When evaluated by polyp subtype, T2DM diagnosis was not associated with the risk for adenomas (adjusted OR 1.02; 95% CI 0.70-1.48), but it was inversely associated with the risk for serrated polyps (adjusted OR 0.61, 95% CI 0.40-0.95). There was significant heterogeneity between adenomas and serrated polyps for their association with T2DM (P for heterogeneity=0.0001); however, the associations did not vary by lesion severity within each polyp subtype (advanced vs. non-advanced adenomas, sessile serrated vs. hyperplastic polyps). Also, associations did not differ statistically significantly between treated and non-treated diabetics for either adenomas or serrated polyps, but there was an increased risk for polyps overall among those not taking anti-diabetic medications (adjusted OR 1.26; 95% CI 0.63-2.53). This association was suggestive but did not reach statistical significance. Conclusions: We observed that the risk for serrated polyps was significantly lower among those with a history of diabetes, while there was no observed association between colorectal adenomas and T2DM. This differential association may possibly be due to a variable effect of anti-diabetic medications on serrated pathway lesions, as suggested by the increased risk for polyps among untreated diabetics. Further studies are needed to better understand the mechanistic processes through which diabetes and its treatment may be differentially associated with the development of adenomas and serrated polyps. Citation Format: Sheetal Hardikar, Andrea N. Burnett-Hartman, Stacey A. Cohen, Polly A. Newcomb. Type 2 diabetes and risk of colorectal polyps in a colonoscopy-based study. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A28.