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Background: Hepatitis B virus (HBV) infection is a significant public health problem in third-world countries, including India. The risk of infection among close family members of patients infected with chronic HBV infection is four to six times higher than in the general population. However, literature is scarce regarding the Knowledge, attitude, and practice toward HBV infection among the first-degree relatives of patients suffering from chronic hepatitis B. Hence, this study aimed to assess the knowledge, attitude, and practice regarding hepatitis B virus infection among first-degree relatives of hepatitis B patients. Methods: A cross-sectional, observational study was conducted amongst the 354 first-degree relatives of HBsAg-positive patients. A validated questionnaire consisted of twenty questions of knowledge, seven questions of attitude, and ten practice questions were employed to gather information. Results: The mean knowledge, attitude, and practice (KAP) were significantly better amongst participants aged 55-65 years and those who were educated. There was a positive correlation between knowledge and attitude (r=0.58, p value

Supplementary Figure from Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older Individuals

Low-dose aspirin is recommended by the U.S. Preventive Services Task Force for primary prevention of colorectal cancer in certain individuals. However, broader implementation will require improved precision prevention approaches to identify those most likely to benefit. The major urinary metabolite of PGE2, 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (PGE-M), is a biomarker for colorectal cancer risk, but it is unknown whether PGE-M is modifiable by aspirin in individuals at risk for colorectal cancer. Adults (N = 180) who recently underwent adenoma resection and did not regularly use aspirin or NSAIDs were recruited to a double-blind, placebo-controlled, randomized trial of aspirin at 81 or 325 mg/day for 8–12 weeks. The primary outcome was postintervention change in urinary PGE-M as measured by LC/MS. A total of 169 participants provided paired urine samples for analysis. Baseline PGE-M excretion was 15.9 ± 14.6 (mean ± S.D, ng/mg creatinine). Aspirin significantly reduced PGE-M excretion (−4.7 ± 14.8) compared with no decrease (0.8 ± 11.8) in the placebo group (P = 0.015; mean duration of treatment = 68.9 days). Aspirin significantly reduced PGE-M levels in participants receiving either 81 (−15%; P = 0.018) or 325 mg/day (−28%; P < 0.0001) compared with placebo. In 40% and 50% of the individuals randomized to 81 or 325 mg/day aspirin, respectively, PGE-M reduction reached a threshold expected to prevent recurrence in 10% of individuals. These results support that aspirin significantly reduces elevated levels of PGE-M in those at increased colorectal cancer risk to levels consistent with lower risk for recurrent neoplasia and underscore the potential utility of PGE-M as a precision chemoprevention biomarker. The ASPIRED trial is registered as NCT02394769.

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Although aspirin has been considered a promising agent for prevention of colorectal cancer, recent data suggest a lack of benefit among older individuals. Whether some individuals with higher risk of colorectal cancer may benefit from aspirin remains unknown. We used a 95-variant colorectal cancer polygenic risk score (PRS) to explore the association between genetic susceptibility to colorectal cancer and aspirin use in a prospective study of 12,609 individuals of European descent ages ≥70 years, enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) double-blinded, placebo-controlled randomized trial (randomized controlled trial; RCT). Cox proportional hazards models were used to assess the association of aspirin use on colorectal cancer, as well as the interaction between the PRS and aspirin treatment on colorectal cancer. Over a median of 4.7 years follow-up, 143 participants were diagnosed with incident colorectal cancer. Aspirin assignment was not associated with incidence of colorectal cancer overall [HR = 0.94; 95% confidence interval (CI), 0.68–1.30] or within strata of PRS (P for interaction = 0.97). However, the PRS was associated with an increased risk of colorectal cancer (HR = 1.28 per SD; 95% CI, 1.09–1.51). Individuals in the top quintile of the PRS distribution had an 85% higher risk compared with individuals in the bottom quintile (HR = 1.85; 95% CI, 1.08–3.15). In a prospective RCT of older individuals, a PRS is associated with incident colorectal cancer risk, but aspirin use was not associated with a reduction of incident colorectal cancer, regardless of baseline genetic risk.Prevention Relevance:There is strong evidence to support prophylactic aspirin use for the prevention of colorectal cancer. However recent recommendations suggest the risk of bleeding in older individuals outweighs the benefit. We sought to determine whether some older individuals might still benefit from aspirin based on their genetic susceptibility.

Branched-chain amino acids (BCAA) are essential amino acids, and emerging evidence suggests that BCAAs may mediate pathways related to cancer progression, possibly due to their involvement in insulin metabolism. We investigated the association between dietary intake of BCAAs with colorectal cancer risk in three prospective cohorts: the Nurses' Health Study I [(NHS), number of participants (n) at baseline = 77,017], NHS II (n = 92,984), and the Health Professionals Follow-up Study [(HPFS) n = 47,255]. Validated food frequency questionnaires were administered every 4 years and follow-up questionnaires on lifestyle biennially. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression models. Pooled HRs were obtained using random effect models. After up to 28 years of follow-up, 1,660 cases were observed in NHS, 306 in NHS II, and 1,343 in HPFS. In multivariable adjusted models, we observed a weak inverse association between BCAA intake and colorectal cancer [highest vs. lowest quintile, pooled HR including all three cohorts (95% CI): 0.89 (0.80–1.00), Ptrend = 0.06, HR per standard deviation (SD) increment 0.95 (0.92–0.99)]. However, after including dairy calcium to the models, BCAA intake was no longer associated with risk of colorectal cancer [HR 0.96 (0.85–1.08), Ptrend = 0.50, HR per SD increment 0.97 (0.93–1.01)]. We did not find evidence that higher dietary BCAA intake is associated with higher risk of colorectal cancer. As this is the first prospective study to examine the association between BCAA intake and colorectal cancer, our findings warrant investigation in other cohorts.

Supplemental Methods, References, Figure, and Tables

Supplemental Table 1: Detailed characteristics of studies included in the ASSET meta-analysis of DNA damage repair and signaling genes. Supplemental Table 2: DNA repair gene, region, and final SNP selection data, using human reference genome assembly, GRCh38. Supplemental Table 3: List of all DNA repair genes and DNA repair pathways included in this study. Supplemental Table 4: Statistical associations (p-values) for cancer risk versus genetic variation within DNA repair pathways. Sensitivity analysis of Table 3, with RAD51B, MSH5, and BRCA2 gene removed from analysis. Statistically significant values are in bold (p < 0.05). Supplemental Table 5: Statistical associations (p-values) for cancer risk versus genetic variation within DNA repair pathways. Sensitivity analysis of Table 3, with 6 genes removed from the analysis -- all genes containing loci with individual SNP associations of p < 1 x 10-4. Statistically significant values are in bold (p < 0.05).

Background: Genome-wide association studies (GWAS) have identified numerous prostate cancer susceptibility alleles, but these loci have been identified primarily in men of European descent. There is limited information about the role of these loci in men of African descent.Methods: We identified 7,788 prostate cancer cases and controls with genotype data for 47 GWAS-identified loci.Results: We identified significant associations for SNP rs10486567 at JAZF1, rs10993994 at MSMB, rs12418451 and rs7931342 at 11q13, and rs5945572 and rs5945619 at NUDT10/11. These associations were in the same direction and of similar magnitude as those reported in men of European descent. Significance was attained at all reported prostate cancer susceptibility regions at chromosome 8q24, including associations reaching genome-wide significance in region 2.Conclusion: We have validated in men of African descent the associations at some, but not all, prostate cancer susceptibility loci originally identified in European descent populations. This may be due to the heterogeneity in genetic etiology or in the pattern of genetic variation across populations.Impact: The genetic etiology of prostate cancer in men of African descent differs from that of men of European descent. Cancer Epidemiol Biomarkers Prev; 20(1); 23–32. ©2011 AACR.

Supplementary Materials from Validation of Genome-Wide Prostate Cancer Associations in Men of African Descent

Background: The CpG island methylator phenotype (CIMP) represents a subset of colorectal cancers characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not known.Methods: We measured the CIMP status of 3,119 primary population-based colorectal cancer tumors from the multinational Colon Cancer Family Registry. Etiologic heterogeneity was assessed by a case–case study comparing risk factor frequency of colorectal cancer cases with CIMP and non-CIMP tumors using logistic regression to estimate the case–case odds ratio (ccOR).Results: We found associations between tumor CIMP status and MSI-H (ccOR = 7.6), BRAF V600E mutation (ccOR = 59.8), proximal tumor site (ccOR = 9; all P < 0.0001), female sex [ccOR = 1.8; 95% confidence interval (CI), 1.5–2.1], older age (ccOR = 4.0 comparing over 70 years vs. under 50; 95% CI, 3.0–5.5), and family history of CRC (ccOR = 0.6; 95% CI, 0.5–0.7). While use of NSAIDs varied by tumor CIMP status for both males and females (P = 0.0001 and P = 0.02, respectively), use of multivitamin or calcium supplements did not. Only for female colorectal cancer was CIMP status associated with increased pack-years of smoking (Ptrend < 0.001) and body mass index (BMI; Ptrend = 0.03).Conclusions: The frequency of several colorectal cancer risk factors varied by CIMP status, and the associations of smoking and obesity with tumor subtype were evident only for females.Impact: Differences in the associations of a unique DNA methylation–based subgroup of colorectal cancer with important lifestyle and environmental exposures increase understanding of the molecular pathologic epidemiology of this heavily methylated subset of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 512–9. ©2015 AACR.

Background: DNA damage is an established mediator of carcinogenesis, although genome-wide association studies (GWAS) have identified few significant loci. This cross-cancer site, pooled analysis was performed to increase the power to detect common variants of DNA repair genes associated with cancer susceptibility.Methods: We conducted a cross-cancer analysis of 60,297 single nucleotide polymorphisms, at 229 DNA repair gene regions, using data from the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) Network. Our analysis included data from 32 GWAS and 48,734 controls and 51,537 cases across five cancer sites (breast, colon, lung, ovary, and prostate). Because of the unavailability of individual data, data were analyzed at the aggregate level. Meta-analysis was performed using the Association analysis for SubSETs (ASSET) software. To test for genetic associations that might escape individual variant testing due to small effect sizes, pathway analysis of eight DNA repair pathways was performed using hierarchical modeling.Results: We identified three susceptibility DNA repair genes, RAD51B (P < 5.09 × 10−6), MSH5 (P < 5.09 × 10−6), and BRCA2 (P = 5.70 × 10−6). Hierarchical modeling identified several pleiotropic associations with cancer risk in the base excision repair, nucleotide excision repair, mismatch repair, and homologous recombination pathways.Conclusions: Only three susceptibility loci were identified, which had all been previously reported. In contrast, hierarchical modeling identified several pleiotropic cancer risk associations in key DNA repair pathways.Impact: Results suggest that many common variants in DNA repair genes are likely associated with cancer susceptibility through small effect sizes that do not meet stringent significance testing criteria. Cancer Epidemiol Biomarkers Prev; 25(1); 193–200. ©2015 AACR.

Supplemental Table 1. Distribution of CIMP status1 by selected characteristics

Supplemental Figure 1: Manhattan plot, illustrating p-values from 60,297 SNP associations, generated from each of the 10 studies used in the meta-analysis. Statistical significance threshold is denoted by the red line (p = 5.09 x 10-6).

Tobacco smoking is the most important and well-established bladder cancer risk factor and a rich source of chemical carcinogens and reactive oxygen species that can induce damage to DNA in urothelial cells. Therefore, common variation in DNA repair genes might modify bladder cancer risk. In this study, we present results from meta-analyses and pooled analyses conducted as part of the International Consortium of Bladder Cancer. We included data on 10 single nucleotide polymorphisms corresponding to seven DNA repair genes from 13 studies. Pooled analyses and meta-analyses included 5,282 cases and 5,954 controls of non-Latino white origin. We found evidence for weak but consistent associations with ERCC2 D312N [rs1799793; per-allele odds ratio (OR), 1.10; 95% confidence interval (95% CI), 1.01–1.19; P = 0.021], NBN E185Q (rs1805794; per-allele OR, 1.09; 95% CI, 1.01–1.18; P = 0.028), and XPC A499V (rs2228000; per-allele OR, 1.10; 95% CI, 1.00–1.21; P = 0.044). The association with NBN E185Q was limited to ever smokers (interaction P = 0.002) and was strongest for the highest levels of smoking dose and smoking duration. Overall, our study provides the strongest evidence to date for a role of common variants in DNA repair genes in bladder carcinogenesis. [Cancer Res 2009;69(17):6857–64]

Supplementary Tables 1-8 from Polymorphisms in DNA Repair Genes, Smoking, and Bladder Cancer Risk: Findings from the International Consortium of Bladder Cancer

Supplementary Figure Legend from Polymorphisms in DNA Repair Genes, Smoking, and Bladder Cancer Risk: Findings from the International Consortium of Bladder Cancer

Supplementary Figure 1 from Polymorphisms in DNA Repair Genes, Smoking, and Bladder Cancer Risk: Findings from the International Consortium of Bladder Cancer

To examine whether the cross-sectional gene-diet interaction for prevalent hyperuricemia among women translates prospectively to risk of incident female gout.We analyzed the interaction between genetic predisposition and adherence to a healthy dietary pattern (i.e., Dietary Approaches to Stop Hypertension [DASH] score) on risk of incident female gout in 18,244 women from Nurses' Health Study (NHS; discovery) and 136,786 women from 3 additional prospective female cohorts from US and UK (replication). Genetic risk score (GRS) was calculated from 114 urate-associated loci.In the NHS and replication cohorts, association between diet and gout risk was larger and stronger among women with higher genetic risk. In all cohorts combined, compared with women with unhealthy DASH score (mean), multivariable relative risk (mRR) for incident female gout among women with healthy DASH score (≥mean) was 0.67 (95% CI 0.60-0.76) among higher GRS (≥mean) and 0.91 (0.78-1.05) among lower GRS (P multiplicative interaction=0.001); mRR for higher vs. lower GRS was 2.03 (1.80-2.29) and 1.50 (1.31-1.71) among unhealthy and healthy DASH score groups, respectively. Additive interaction was also significant, in both the discovery and replication cohorts (P0.001), with 51% of the excess risk attributable to the additive gene-diet interaction in all cohorts combined.The deleterious effect of genetic predisposition on risk of incident female gout was more pronounced among women with unhealthy diet, with nearly half the excess risk attributable to this gene-diet interaction. These data elucidate the important synergy of genetics and diet for female gout development. This article is protected by copyright. All rights reserved.

How metabolome changes influence the early process of colorectal cancer (CRC) development remains unknown. We conducted a 1:2 matched nested case-control study to examine the associations of pre-diagnostic plasma metabolome (profiled using LC-MS) with risk of CRC precursors, including conventional adenomas (n = 586 vs. 1141) and serrated polyps (n = 509 vs. 993), in the Nurses' Health Study (NHS) and NHSII. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). We used the permutation-based Westfall and Young approach to account for multiple testing. Subgroup analyses were performed for advanced conventional adenomas (defined as at least one adenoma of ≥ 10 mm or with high-grade dysplasia, or tubulovillous or villous histology) and high-risk serrated polyps that were located in the proximal colon or with size of ≥ 10 mm. After multiple testing correction, among 207 metabolites, higher levels of C36:3 phosphatidylcholine (PC) plasmalogen were associated with lower risk of conventional adenomas, with the OR (95% CI) comparing the 90th to the 10th percentile of 0.62 (0.48-0.81); C54:8 triglyceride (TAG) was associated with higher risk of serrated polyps (OR = 1.79, 95% CI: 1.31-2.43), and phenylacetylglutamine (PAG) was associated with lower risk (OR = 0.57, 95% CI:0.43-0.77). PAG was also inversely associated with advanced adenomas (OR = 0.57, 95% CI: 0.36-0.89) and high-risk serrated polyps (OR = 0.54, 95% CI: 0.32-0.89), although the multiple testing-corrected p value was 0.05. Our findings suggest potential roles of lipid metabolism and phenylacetylglutamine, a microbial metabolite, in the early stage of colorectal carcinogenesis, particularly for the serrated pathway.

Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1–28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose–response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06–1.17; OR for AA genotype = 1.22; 95% CI, 1.14–1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.

Objectives Gout prevalence is reportedly ∼20% higher in US Black adults than Whites, but racial differences in emergency department (ED) visits and hospitalizations for gout are unknown. We evaluated the latest US national utilization datasets according to racial/ethnic groups. Methods Using 2019 US National Emergency Department Sample and National Inpatient Sample databases, we compared racial/ethnic differences in annual population rates of ED visits and hospitalizations for gout (primary discharge diagnosis) per 100 000 US adults (using 2019 age- and sex-specific US census data). We also examined rates of ED visits and hospitalizations for gout among all US ED visits/hospitalizations and mean costs for each gout encounter. Results Compared with White patients, the per capita age- and sex-adjusted rate ratio (RR) of gout primary ED visits for Black patients was 5.01 (95% CI 4.96, 5.06), for Asian patients 1.29 (1.26, 1.31) and for Hispanic patients 1.12 (1.10, 1.13). RRs for gout primary hospitalizations were 4.07 (95% CI 3.90, 4.24), 1.46 (1.34, 1.58) and 1.06 (0.99, 1.13), respectively. Corresponding RRs among total US hospitalizations were 3.17 (95% CI 2.86, 3.50), 3.23 (2.71, 3.85) and 1.43 (1.21, 1.68) and among total ED visits were 2.66 (95% CI, 2.50, 2.82), 3.28 (2.64, 4.08), and 1.14 (1.05, 1.24), respectively. RRs were largest among Black women. Costs for ED visits and hospitalizations experienced by race/ethnicity showed similar disparities. Conclusions These first nationwide data found a substantial excess in both gout primary ED visits and hospitalizations experienced by all underserved racial/ethnic groups, particularly by Black women, revealing an urgent need for improved care to eliminate inequities in gout outcomes.

ImportanceGout disparities among Black individuals in the US have recently been explained by socioclinical factors; however, no information is available among Asian individuals living in Western countries, despite their disproportionately worsening metabolic health.ObjectiveTo determine the prevalence of gout and serum urate concentrations according to race and ethnicity and to explore the association of social determinants of health and clinical factors.Design, Setting, and ParticipantsThis is a population-based, cross-sectional analysis. Data from a nationally representative sample of US adults were obtained from the National Health and Nutrition Examination Survey (NHANES) (2011-2018) in which Asian race data were collected (primary). Data from the UK Biobank (2006-2021) were used for replication of the Asian vs White differences. Data analysis was performed from December 2021 to September 2022.Main Outcomes and MeasuresRace-specific gout prevalence and serum urate levels.ResultsA total of 22 621 participants from NHANES (2011-2018) were included in the analysis (mean [SD] age, 49.8 [17.8] years; 10 948 male participants [48.4%]). In 2017 to 2018, gout affected 12.1 million US individuals, with its crude prevalence increasing from 3.6% (95% CI, 2.8%-4.5%) in 2011 to 2012 to 5.1% (95% CI, 4.2%-5.9%) in 2017 to 2018 (P for trend = .03); this trend was no longer significant after age adjustment (P for trend = .06) or excluding Asian individuals (P for trend = .11). During the same period, age- and sex-adjusted prevalence among Asian Americans doubled from 3.3% (95% CI, 2.1%-4.5%) to 6.6% (95% CI, 4.4%-8.8%) (P for trend = .007) to numerically exceed all other racial and ethnic groups in 2017 to 2018, with age- and sex-adjusted odds ratio (ORs) of 1.61 (95% CI, 1.03-2.51) and a socioclinical factor–adjusted multivariable OR of 2.62 (95% CI, 1.59-4.33) for Asian vs White individuals. The latest age- and sex-adjusted gout prevalence among US individuals aged 65 years and older was 10.0% among White individuals and 14.8% among Asian individuals (including 23.6% of Asian men). Serum urate concentrations also increased between 2011 and 2018 among US Asian individuals (P for trend = .009). The Asian vs White disparity was also present in the UK Biobank.Conclusions and RelevanceThe findings of this study suggest that the prevalence of gout among Asian individuals numerically surpassed that for all other racial and ethnic groups in 2017 to 2018. This Asian vs White disparity did not appear to be associated with socioclinical factors.

Background: Metabolic disturbance and inflammation may explain observed associations between higher body mass index (BMI) and increased risk of colorectal cancer (CRC); however, the underlying mechanisms are not fully understood. Objectives: We characterized individual plasma metabolites and metabolomic signatures of metabolic disturbance and inflammation and evaluated their association with prospective CRC risk within the Nurses’ Health Study and the Health Professionals Follow-up Study. Methods: Among 686 colorectal cancer cases and 686 age-matched controls, we used reduced rank regression of markers of metabolic disturbance (BMI, waist circumference, C-peptide, and adiponectin) or inflammation (BMI, C-reactive protein, interleukin-6, and tumor necrosis factor receptor superfamily member 1B) with cross-sectional measures of 353 plasma metabolites to develop a Y-score for metabolic disturbance and Y-score for inflammation among men and women separately. We then used elastic net regression to derive a signature of metabolites, and multiple linear regression to identify individual metabolites, associated with each Y-score. We evaluated the association of individual metabolites and the metabolomic signatures with odds of CRC using conditional logistic regression adjusted for other CRC risk factors. Results: The metabolomic signature of metabolic disturbance consisted of 41 metabolites selected via elastic net regression in men and 72 in women; the metabolomic signature of inflammation consisted of 68 metabolites in men and 119 in women. The metabolic disturbance metabolomic signatures captured, on average, 36% of variation in markers of metabolic disturbance in women and 35% in men; the inflammation signature captured 35% of variation in inflammatory markers in women and 26% in men. The metabolomic signature of metabolic disturbance was associated with increased odds of CRC (odds ratio (OR) comparing highest to lowest quartile = 1.63; 95% confidence interval (CI), 0.92, 2.91; Ptrend = 0.31) and the metabolomic signature of inflammation was associated with increased odds of CRC (OR = 2.01; 95% CI, 1.14, 3.57; Ptrend = 0.008) among men. Neither signature was associated with CRC among women. Of the metabolites associated with metabolic disturbance and inflammation, 13 metabolites were also associated with CRC: 4 metabolites classified as uremic toxins (2 purine nucleosides and 2 amino acid derivates); 3 sphingolipids; 3 glycerophospholipids; 2 sterols related to cholesterol homeostasis; and 3-ureidopropanoate, a uracil metabolism substrate. Conclusion: We identified plasma metabolomic signatures and individual metabolites associated with metabolic disturbance, inflammation, and CRC risk, highlighting pathways such as protein metabolism and lipid homeostasis that may relate adiposity-related metabolic disturbance and inflammation to CRC development. Citation Format: Alaina M. Bever, Dong Hang, Amit D. Joshi, Connor M. Geraghty, Dong Hoon Lee, Fred K. Tabung, Shuji Ogino, Jeffrey A. Meyerhardt, Andrew T. Chan, Edward L. Giovannucci, A. Heather Eliassen, Liming Liang, Meir J. Stampfer, Mingyang Song. Metabolomic signatures of metabolic disturbance and inflammation in relation to colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3006.

Background and Aims Microscopic colitis (MC) is an inflammatory bowel disease and a common cause of chronic diarrhea. Appendectomy has been suggested to have immunomodulating effects in the colon, influencing the risk of gastrointestinal disease. The relationship between appendectomy and MC has only been sparsely studied. Methods This was a case-control study based on the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, consisting of histopathological examinations in Sweden, linked to national registers. Patients with MC were matched to population controls by age, sex, calendar year of biopsy, and county of residence. Data on antecedent appendectomy and comorbidities were retrieved from the Patient Register. Unconditional logistic regression models were conducted presenting odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for country of birth and matching factors. Further subanalyses were made based on MC subtypes (lymphocytic colitis and collagenous colitis), follow-up time postappendectomy and severity of appendicitis. Results The study included 14,520 cases of MC and 69,491 controls, among these 7.6% (n = 1103) and 5.1% (n = 3510), respectively, had a previous appendectomy ≥1 year prior to MC or matching date. Patients with a previous appendectomy had an increased risk of MC in total (OR, 1.50; 95% CI, 1.40–1.61) and per the collagenous colitis subtype (OR, 1.67; 95% CI, 1.48–1.88) or lymphocytic colitis subtype (OR, 1.42; 95% CI, 1.30–1.55). The risk remained elevated throughout follow-up, and the highest risk was observed in noncomplicated appendicitis. Conclusions This nationwide case-control study found a modestly increased risk of developing MC following appendectomy.