Multivariable Conditional Logistic Regression Models Research Articles

Severe COVID-19 outcomes among patients with autoimmune rheumatic diseases or transplantation: a population-based matched cohort study

ObjectivesTo assess the risk of severe COVID-19 outcomes in patients with autoimmune rheumatic diseases (ARDs) and transplant recipients compared with matched general population comparators.DesignPopulation-based matched cohort study using administrative health...

Publication in the Australian medical student journal is associated with future academic success: a matched-cohort study

BackgroundMedical student journals (MSJs) help to introduce the fundamentals of academic research and publication to future doctors. It has recently been shown that MSJs can influence doctors’ future academic and professional success, however these findings have not been replicated in an Australian cohort. The aim of this study was to examine the association between publication in the Australian Medical Student Journal (AMSJ) and markers of a student’s future academic trajectory, including future publication, attainment of higher academic degree or entry into specialist training.MethodsArticles authored by medical students in the AMSJ from 2010 to 2015 were retrospectively identified. A list of these student authors was made, with university- and year- matched control students randomly selected from university graduation databases. For all students, data related to academic success were obtained from multiple sources including PubMed®, Google, university databases and author affiliation information from publications. A multivariable conditional logistic regression model was used to assess correlation between variables. The primary outcome measure was the number of postgraduate PubMed®-indexed publications. Secondary outcome measures included attainment of higher degree or faculty position. Clinical speciality was also recorded.ResultsFifty-five AMSJ authors (14 case reports, 17 original research, 21 review articles) from 14 Australian universities were included. Publication in the AMSJ was associated with future PubMed® indexed publications (OR 3.43, 95% CI 1.74–6.77, P < 0.001) and higher degree attainment (OR 4.05, 95% CI 1.99–8.22, P = 0.0001). AMSJ authors were also significantly more likely to enter into surgical training (OR 2.53, 95% CI 1.10–5.84, P = 0.029). A multivariable conditional logistic regression model demonstrated that publication in the AMSJ was predictive of future PubMed indexed publication, independent of higher degree or faculty position attainment (OR 2.56, CI 1.22–5.39, P = 0.01).ConclusionWe have shown that publication in a MSJ is associated with markers of academic success in an Australian cohort. PubMed®-indexed publications, attainment of a Masters degree, and entry in to surgical training were all significantly correlated to AMSJ publication. A conditional logistic regression model demonstrated that medical student publication in the AMSJ influences the number of future PubMed®-indexed publications, independent of major academic confounding variables.

Urinary Excretion of Cyanuric Acid in Association with Urolithiasis: A Matched Case-Control Study in Shanghai Adults.

Melamine (MEL) has raised human concern since the 2008 milk scandal. Co-exposure to MEL and one of its analogues, cyanuric acid (CYA), has been reported to have a synergistic effect on promoting urolithiasis. However, few epidemiological studies have reported urolithiasis in association with exposure to CYA based on our knowledge. We therefore conducted a case-control study to investigate whether cases of urolithiasis had higher excretion of urinary CYA than the controls. Spot urine samples from 70 adult cases and first-morning urine samples from 70 controls (matched by age and sex) were collected for the measurement of MEL, CYA, and other two analogues in urine. The case group also had 2.81-fold higher concentration of urinary CYA than the control group (34.87 versus 12.43 ng/mL, p-value < 0.001). Multivariate conditional logistic regression models adjusting potential confounders of personal characteristics identified the risk factor of urinary CYA as a continuous variable with odds ratio (OR) (95% confidence interval, 95%CI) of 1.11 (1.02–1.21) (p-value = 0.021) and having meals at restaurants with OR of 5.71 (1.01–32.31) (p-value = 0.049). Compared to the participants having the lowest quartile of CYA concentration in urine, participants at the second, third, and fourth quartile groups had ORs of 13.94, 83.69, and 118.65 with p-values of 0.004, <0.001, and <0.001, respectively. The high excretion of urinary CYA in urolithiasis cases might be the sign of stones in patients consisting of CYA, then proving the attribution of CYA exposure in the etiology of urolithiasis. These findings are important since CYA is a degraded by-product of chlorinated isocyanuric acid disinfectants, which are widely used in daily life not only in swimming pool water but also in other scenarios, such as serving as anti-pandemic disinfectants. Risk assessment of CYA serving as a by-product of disinfectants needs to be conducted in future studies.

Prediagnostic plasma polyphenol concentrations and colon cancer risk: The JPHC nested case–control study

Epidemiological studies that assessed the associations between dietary polyphenol intakes and colon cancer risk have reported largely null results, possibly due to measurement error associated with dietary assessment. We adopted an objective approach by measuring prediagnostic plasma concentrations of 35 polyphenols and assessing associations with colon cancer risk. We conducted a nested-case control study within the Japan Public Health Center-based prospective study (JPHC Study) utilizing plasma samples collected at the time of a five-year follow-up survey between 1995 and 1999. We identified colon cancer cases who developed cancer during the follow-up from the time of blood collection. Controls were matched by age, sex, area code, population size of the area, season of blood collection, year of blood collection, and duration of fasting time before the blood collection. Prediagnostic concentrations of 35 polyphenols from 375 incident colon cancer cases (followed until 2012) and 710 matched controls were measured by tandem mass spectrometry coupled with ultra-high-pressure liquid chromatography. We used multivariable conditional logistic regression models adjusted for established colon cancer risk factors to estimate odds ratios (ORs) and 95% confidence intervals (CIs). In sexes combined log2-transformed multivariable models, circulating levels of 3,4-dihydroxyphenylpropionic acid (P=0.02), ferulic acid (P=0.02), and caffeic acid (P=0.03) were inversely, and 3-hydroxybenzoic acid (P=0.03) was positively, associated with colon cancer risk. For men only, circulating levels of 3,4-dihydroxyphenylpropionic acid was inversely, and 3,5-dihydroxyphenylpropionic acid, gallic acid, (+)-epigallocatechin, 3-hydroxybenzoic acid, and epicatechin were positively, associated with colon cancer risk. In women, plasma caffeic acid and ferulic acid concentration were inversely associated with colon cancer risk. However, all these associations were nonsignificant after adjustment for multiple comparisons. The remaining polyphenols were not associated with colon cancer risk. Coffee-derived 3,4-dihydroxyphenylpropionic acid, ferulic acid, and caffeic acid concentrations were inversely associated with colon cancer risk although the association were nonsignificant after adjustment for multiple comparisons. These results support a possible role of coffee polyphenols in preventing colorectal cancer.

Epidemiologic Implication of the Association between Herpes Simplex Virus Infection and the Risk of Type 1 Diabetes Mellitus: A Nationwide Case-Control Study in Taiwan.

Enterovirus infection is a known risk factor for type 1 diabetes (T1DM). Whether infection with other viruses induces T1DM remains undetermined. This study investigated the association between human herpesvirus (HHV) infection and the development of T1DM, using the data from Taiwan’s National Health Insurance Research Database. Patients with T1DM and age- and sex-matched controls were included. Subjects with HHV infection were subgrouped into those with histories of varicella-zoster virus, herpes simplex virus (HSV), Epstein-Barr virus, and human cytomegalovirus infections. The odds ratio of the risk of T1DM was calculated using a multivariable conditional logistic regression model. Atopic diseases, autoimmune thyroid diseases, and history of enterovirus infection served as adjusted comorbidities. Our findings suggested a significant association between HSV infection and the risk of T1DM (adjusted odds ratio: 1.21; 95% CI: 1.01–1.47, p = 0.048), while infection with other HHVs was not. The result of HSV infection remained significant when subjects were restricted to age ≤ 18 years (adjusted odds ratio: 1.35; 95% CI: 1.08–1.70, p = 0.010). We found a history of HSV infection might be an independent predictive risk factor for T1DM. This could be potentially helpful to the practice in public health.

Sex-specific Association of Primary Aldosteronism With Visceral Adiposity.

ContextThe association between primary aldosteronism and obesity, especially its sex difference, remains unknown.ObjectiveTo assess the association for each subtype of primary aldosteronism with obesity parameters including visceral adipose tissue and differences between sexes.MethodsIn this case-control study, 4 normotensive controls were selected for each case with primary aldosteronism. Multivariable conditional logistic regression models were used to estimate the association between each type of primary aldosteronism and obesity indicators. We used a random forest to identify which visceral or subcutaneous tissue areas had a closer association with disease status.ResultsThe study subjects included 42 aldosterone-producing adenoma cases (22 women) and 68 idiopathic hyperaldosteronism cases (42 women). In multivariable conditional logistic regressions, aldosterone-producing adenoma was significantly associated with body mass index only in men (odds ratio [OR] [95% CI)], 4.62 [1.98-10.80] per 2.89 kg/m2) but not in women (OR [95% CI], 1.09 [0.69-1.72] per 3.93 kg/m2) compared with the matched controls, whereas idiopathic hyperaldosteronism was associated with body mass index in both men (OR [95% CI], 3.96 [2.03-7.73] per 3.75 kg/m2) and women (OR [95% CI], 2.65 [1.77-3.96] per 3.85 kg/m2) compared with the matched controls. In random forests, visceral adipose tissue areas were the better predictor of both aldosterone-producing adenoma and idiopathic hyperaldosteronism than subcutaneous adipose tissue.ConclusionsAldosterone-producing adenoma cases were obese among men, but not among women. Idiopathic hyperaldosteronism cases were obese among both men and women. Visceral adipose tissue may contribute to the pathophysiology of primary aldosteronism.

The Impact of Cardiac Dysfunction Based on Killip Classification on Gastrointestinal Bleeding in Acute Myocardial Infarction

BackgroundOwing to limited data, the effect of cardiac dysfunction categorized according to the Killip classification on gastrointestinal bleeding (GIB) in patients with acute myocardial infarction (AMI) is unclear. The present study aimed to investigate the impact of cardiac dysfunction on GIB in patients with AMI and to determine if patients in the higher Killip classes are more prone to it.MethodsThis retrospective study was comprised of patients with AMI who were admitted to the cardiac intensive care unit in the Heart Center of the Beijing Chaoyang Hospital between December 2010 and June 2019. The in-hospital clinical data of the patients were collected. Both GIB and cardiac function, according to the Killip classification system, were confirmed using the discharge diagnosis of the International Classification of Diseases, Tenth Revision coding system. Univariate and multivariate conditional logistic regression models were constructed to test the association between GIB and the four Killip cardiac function classes.ResultsIn total, 6,458 patients with AMI were analyzed, and GIB was diagnosed in 131 patients (2.03%). The multivariate logistic regression analysis showed that the risk of GIB was significantly correlated with the cardiac dysfunction [compared with the Killip class 1, Killip class 2’s odds ratio (OR) = 1.15, 95% confidence interval (CI): 0.73–1.08; Killip class 3’s OR = 2.63, 95% CI: 1.44–4.81; and Killip class 4’s OR = 4.33, 95% CI: 2.34–8.06].ConclusionThis study demonstrates that the degree of cardiac dysfunction in patients with acute myocardial infarction is closely linked with GIB. The higher Killip classes are associated with an increased risk of developing GIB.

Abstract SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

Abstract SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

Tobacco and other risk factors for esophageal squamous cell carcinoma in Lilongwe Malawi: Results from the Lilongwe esophageal cancer case: Control study.

Esophageal cancer is the second commonest cancer in Malawi, and 95% of all cases are esophageal squamous cell carcinoma (ESCC). Very little is known about the epidemiology of ESCC in Malawi including risk factors. The main objective of the study was to evaluate and describe risk factors of ESCC in Malawi. We conducted a case-control study from 2017 to 2020 at two hospitals in Lilongwe, Malawi and consenting adults were eligible for inclusion. Endoscopy was conducted on all cases and biopsies were obtained for histological confirmation. Controls were selected from patients or their guardians in orthopedic, dental and ophthalmology wards and they were frequency matched by sex, age, and region of origin to cases. An electronic structured questionnaire was delivered by a trained interviewer. Multivariate conditional logistic regression models were used to assess the associations between subject characteristics, habits, and medical history and risk of ESCC. During the study period, 300 cases and 300 controls were enrolled into the study. Median age of cases and controls was 56 years and 62% of the cases were male. Among cases, 30% were ever cigarette smokers as were 22% of controls. Smoking cigarettes had an adjusted odds ratio of 2.4 (95% CI 1.4-4.2 p = 0.003). HIV+ status was present in 11% of cases and 4% controls, which resulted in an adjusted odds ratio was 4.0 (95% CI 1.8-9.0 p = 0.001). Drinking hot tea was associated with an adjusted odd ratio of 2.9 (95% CI 1.3-6.3 p = 0.007). Mold on stored grain has an adjusted odd ratio of 1.6 (95% CI 1.1-2.5 p = 0.021). Reducing smoking cigarettes, consumption of scalding hot tea, and consumption of contaminated grain, could potentially help reduce the burden of ESCC in Malawi. Further investigation of the association between HIV status and ESCC are warranted.

A nested case-control study on radiation dose-response for cardiac events in breast cancer patients in Germany

BackgroundPrevious studies with the majority of breast cancer (BC) patients treated up to 2000 provided evidence that radiation dose to the heart from radiotherapy (RT) was linearly associated with increasing risk for long-term cardiac disease. RT techniques changed substantially over time. This study aimed to investigate the dose-dependent cardiac risk in German BC patients treated with more contemporary RT. MethodsIn a cohort of 11,982 BC patients diagnosed in 1998–2008, we identified 494 women treated with 3D-conformal RT who subsequently developed a cardiac event. Within a nested case-control approach, these cases were matched to 988 controls. Controls were patients without a cardiac event after RT until the index date of the corresponding case. Separate multivariable conditional logistic regression models were used to assess the association of radiation to the complete heart and to the left anterior heart wall (LAHW) with cardiac events. ResultsMean dose to the heart for cases with left-sided BC was 4.27 Gy and 1.64 Gy for cases with right-sided BC. For controls, corresponding values were 4.31 Gy and 1.66 Gy, respectively. The odds ratio (OR) per 1 Gy increase in dose to the complete heart was 0.99 (95% confidence interval (CI): 0.94–1.05, P = .72). The OR per 1 Gy increase in LAHW dose was 1.00 (95% CI: 0.98–1.01, P = .68). ConclusionsContrary to previous studies, our study provided no evidence that radiation dose to the heart from 3D-conformal RT for BC patients treated between 1998 and 2008 was associated with risk of cardiac events.

A prospective investigation of serum bile acids with risk of liver cancer, fatal liver disease, and biliary tract cancer.

Bile acids (BAs), major regulators of the gut microbiota, may play an important role in hepatobiliary cancer etiology. However, few epidemiologic studies have comprehensively examined associations between BAs and liver or biliary tract cancer. In the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) study, we designed 1:1 matched, nested, case–control studies of primary liver cancer (n = 201 cases), fatal liver disease (n = 261 cases), and primary biliary tract cancer (n = 138 cases). Using baseline serum collected ≤30 years before diagnosis or death, we measured concentrations of 15 BAs with liquid chromatography–tandem mass spectrometry. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable conditional logistic regression models, adjusted for age, education, diabetes status, smoking, alcohol intake, and body mass index. We accounted for multiple comparisons using a false discovery rate (FDR) correction. Comparing the highest to the lowest quartile, seven BAs were positively associated with liver cancer risk, including taurocholic acid (TCA) (OR, 5.62; 95% CI, 2.74–11.52; Q trend < 0.0001), taurochenodeoxycholic acid (TCDCA) (OR, 4.77; 95% CI, 2.26–10.08; Q trend < 0.0001), and glycocholic acid (GCA) OR, 5.30; 95% CI, 2.41–11.66; Q trend < 0.0001), and 11 were positively associated with fatal liver disease risk, including TCDCA (OR, 9.65; 95% CI, 4.41–21.14; Q trend < 0.0001), TCA (OR, 7.45; 95% CI, 3.70–14.97; Q trend < 0.0001), and GCA (OR, 6.98; 95% CI, 3.32–14.68; Q trend < 0.0001). For biliary tract cancer, associations were generally >1 but not significant after FDR correction. Conjugated BAs were strongly associated with increased risk of liver cancer and fatal liver disease, suggesting mechanistic links between BA metabolism and liver cancer or death from liver disease.

Vulnerability Predictors of Post-Vaccine SARS-CoV-2 Infection and Disease-Empirical Evidence from a Large Population-Based Italian Platform.

We aimed to identify individual features associated with increased risk of post-vaccine SARS-CoV-2 infection and severe COVID-19 illness. We performed a nested case–control study based on 5,350,295 citizens from Lombardy, Italy, aged ≥ 12 years who received a complete anti-COVID-19 vaccination from 17 January 2021 to 31 July 2021, and followed from 14 days after vaccine completion to 11 November 2021. Overall, 17,996 infections and 3023 severe illness cases occurred. For each case, controls were 1:1 (infection cases) or 1:10 (severe illness cases) matched for municipality of residence and date of vaccination completion. The association between selected predictors (sex, age, previous occurrence of SARS-CoV-2 infection, type of vaccine received, number of previous contacts with the Regional Health Service (RHS), and the presence of 59 diseases) and outcomes was assessed by using multivariable conditional logistic regression models. Sex, age, previous SARS-CoV-2 infection, type of vaccine and number of contacts with the RHS were associated with the risk of infection and severe illness. Moreover, higher odds of infection and severe illness were significantly associated with 14 and 34 diseases, respectively, among those investigated. These results can be helpful to clinicians and policy makers for prioritizing interventions.

Risk factors for candidemia: A case–control study

Background:Candida bloodstream infections (candidemia) have significant mortality and morbidity rates, as well as healthcare cost implications. Emerging multidrug-resistant Candida spp such as Candida auris, as well as increasing resistance among non–albicans species, which are becoming more prevalent, also raise concern. Understanding the epidemiology of this infection could enhance prevention and management efforts. We studied risk factors for candidemia. Methods: This matched case–control study was conducted at a university hospital from December 2019 through May 2021. Cases of candidemia were identified using positive blood-culture results. Controls were matched 5:1 to cases by age, sex, and month and year of admission. Risk factors of interest included total parenteral nutrition (TPN), central venous access (CVA), neutropenia, Clostridium difficile, pancreatic disease, Candida in urine culture, cancer, invasive procedures, H2 blockers, chemotherapy, antibiotic use, immunosuppression, and antifungal use. Bivariate conditional logistic regression models were used to study the association of individual factors with candidemia. Multivariable conditional logistic regression models were performed using factors with a P Results: Overall, 101 patients with candidemia and 505 matched controls were included. In the bivariate analysis, associations were detected between candidemia and TPN, CVA, pancreatic disease, invasive procedures, H2 blocker use, antibiotic use, and antifungal use (all Ps Conclusions: Associations of candidemia with recent antifungal use and pancreatic disease were relatively novel findings. Neutropenia was not an independent risk factor for candidemia in this study. Future directions include further evaluations of previous antifungal use in patients with candidemia to identify opportunities for possible intervention and antifungal stewardship.Funding: NoneDisclosures: None

The role of the genetic variant FECH rs11660001 in the occurrence of anti-tuberculosis drug-induced liver injury.

The pathogenic mechanism of anti-tuberculosis drug-induced liver injury (AT-DILI) is still largely unknown. Recent studies have indicated that rifampicin and isoniazid cotreatment causes the accumulation of endogenous protoporphyrin IX in the liver through the haem biosynthesis pathway. Alanine synthase 1 (ALAS1) and ferrochelatase (FECH) are the rate-limiting enzymes in the production of haem. The present study aimed to investigate the genetic contribution of the ALAS1 and FECH genes to the risk of AT-DILI in an Eastern Chinese Han population. A 1:4 matched case-control study was conducted, and eight SNPs in the ALAS1 and FECH genes were detected and assessed. A multivariate conditional logistic regression model was used to estimate the association between genotypes and the risk of AT-DILI by the odds ratios (ORs) with 95% confidence intervals (CIs), with liver disease history, hepatoprotectant use, smoking and drinking history as covariates. Overall, 202 AT-DILI cases and 808 controls were included in this study. The female patients carrying polymorphisms of rs11660001 in FECH had an increased risk of AT-DILI under the dominant and additive models (OR=1.831, 95% CI: 1.014-3.307, p=0.045; OR=1.673, 95% CI: 1.015-2.760, p=0.044, respectively). The peak aspartate transaminase level was significantly higher in female patients carrying the GA+AA genotype of rs11660001 than in those with the GG genotype during anti-TB treatment (p=0.032). Based on this 1:4 individual matched case-control study, SNP rs11660001 in the FECH gene may be associated with susceptibility to AT-DILI in Chinese female anti-TB treatment patients. Further studies in larger varied populations are needed to validate our findings.

Corticosteroids and Other Treatments Administered to Children Tested for SARS-CoV-2 Infection in Emergency Departments.

ObjectiveWe sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children.MethodsWe collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were <18 years old, had signs or symptoms of, or risk factors for acute SARS-CoV-2 infection, and had nucleic acid testing performed. To determine if SARS-CoV-2 test status was independently associated with corticosteroid administration, we used a multivariable conditional logistic regression model matched by study site to compare treatments administered based on SARS-CoV-2 test and disposition status. This analysis was repeated for the subgroup of study participants who were hospitalized.Results30.3% (3,121/10,315) of participants were SARS-CoV-2-positive. Although remdesivir was more commonly administered to SARS-CoV-2-positive children, use was infrequent (25/3120 [0.8%] vs 1/7188 [0.01%]; P = .001). Corticosteroid use was less common among SARS-CoV-2-positive children (219/3120 [7.0%] vs 759/7190 [10.6%]; P < .001). Among hospitalized children, there were no differences in provision of inotropes, respiratory support, chest drainage or extracorporeal membrane oxygenation between groups. Corticosteroid administration was associated with age, history of asthma, wheezing, study month, hospitalization and intensive care unit admission; it was not associated with a positive SARS-CoV-2 test result overall (aOR: 0.91; 95%CI: 0.74, 1.12) or among the subgroup of those hospitalized (aOR: 1.04; 95%CI: 0.75, 1.44).ConclusionsFew disease-specific treatments are provided to SARS-CoV-2-positive children; clinical trials evaluating therapies in children are urgently needed.

Predicting the Risk of Microtia From Prenatal Factors: A Hospital-Based Case-Control Study

BackgroundAlthough a wide range of risk factors for microtia were identified, the limitation of these studies, however, is that risk factors were not estimated in comparison with one another or from different domains. Our study aimed to uncover which factors should be prioritized for the prevention and intervention of non-syndromic microtia via tranditonal and meachine-learning statistical methods.Methods293 pairs of 1:1 matched non-syndromic microtia cases and controls who visited Shanghai Ninth People's Hospital were enrolled in the current study during 2017-2019. Thirty-nine risk factors across four domains were measured (i.e., parental sociodemographic characteristics, maternal pregnancy history, parental health conditions and lifestyles, and parental environmental and occupational exposures). Lasso regression model and multivariate conditional logistic regression model were performed to identify the leading predictors of microtia across the four domains. The area under the curve (AUC) was used to calculate the predictive probabilities.ResultsEight predictors were identified by the lasso regression, including abnormal pregnancy history, genital system infection, teratogenic drugs usage, folic acid supplementation, paternal chronic conditions history, parental exposure to indoor decoration, paternal occupational exposure to noise and maternal acute respiratory infection. The additional predictors identified by the multivariate conditional logistic regression model were maternal age and maternal occupational exposure to heavy metal. Predictors selected from the conditional logistic regression and lasso regression both yielded AUCs (95% CIs) of 0.83 (0.79–0.86).ConclusionThe findings from this study suggest some factors across multiple domains are key drivers of non-syndromic microtia regardless of the applied statistical methods. These factors could be used to generate hypotheses for further observational and clinical studies on microtia and guide the prevention and intervention strategies for microtia.

Endogenous sex hormones, aromatase activity and lung cancer risk in postmenopausal never-smoking women.

Although reproductive factors have been repeatedly associated with lung cancer risk, no study to date has directly evaluated the relationship with endogenous sex hormones nor with aromatase activity in postmenopausal never-smoking women. A case-control study of 397 incident lung cancer cases and their individually matched controls, nested within the Shanghai Women's Health Study, was conducted among postmenopausal women who were lifetime never smokers. Prediagnostic concentrations of sex hormones was quantitated using LC-MS/MS assays in plasma. The product-substrate molar ratio of estrone to androstenedione was used as an index of aromatase activity (IAA). Multivariable conditional logistic regression models were used to calculate odds ratios (ORs) for lung cancer. Baseline concentrations of estradiol, free testosterone and IAA were inversely associated with subsequent risk of lung cancer in multivariable-adjusted models. When further adjusted for body mass index, the inverse association with estradiol was attenuated and no longer statistically significant, but the association with free testosterone and IAA remained. In analyses confined to participants having never used menopausal hormone therapy in 376 case-control pairs, the inverse association with free testosterone and IAA was slightly strengthened. OR for the highest vs the lowest quartile of free testosterone was 0.55 (95% CI=0.34-0.90; Ptrend =.03), and the corresponding OR for IAA was 0.57 (95% CI=0.34-0.96; Ptrend =.04). Our study, for the first time, suggests that higher levels of circulating free testosterone and estimated aromatase activity may be associated with lower lung cancer risk in postmenopausal never-smoking women.

Prospective Associations of Circulating Bile Acids and Short-Chain Fatty Acids With Incident Colorectal Cancer.

Human studies investigating the prospective relationship between microbial metabolites and colorectal cancer (CRC) risk are lacking. We tested whether higher serum bile acids (BAs) and lower short-chain fatty acids (SCFAs) were associated with CRC risk. In baseline serum collected more than 30 years before a CRC diagnosis, we quantified concentrations of 15 BAs and 6 SCFAs using targeted liquid chromatography with tandem mass spectrometry assays in 1:1 matched cases and controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial (men: n = 262 cases; women: n = 233 cases) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (men: n = 598 cases). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for BA and SCFA quartiles and summary measures with CRC overall and by anatomic location using multivariable conditional logistic regression models. PLCO analyses were stratified by sex. All statistical tests were 2-sided. In PLCO women, 7 BAs were strongly associated with increased CRC risk, including the secondary BAs, deoxycholic (ORQ4 v Q1 = 2.85, 95% CI = 1.45 to 5.60, Qtrend = 0.011), glycodeoxycholic (OR Q4 v Q1 = 3.45, 95% CI = 1.79 to 6.64, Qtrend = 0.006), taurodeoxycholic (OR Q4 v Q1 = 2.36, 95% CI = 1.22 to 4.55, Qtrend = 0.023), and glycolithocholic acid (ORQ4 v Q1 = 2.71, 95% CI = 1.41 to 5.22, Qtrend = 0.015). Women in the highest compared with lowest quartile of total SCFAs had a 45% lower risk of CRC (OR = 0.55, 95% CI = 0.31 to 0.98, Ptrend = .03). Associations for total BAs and SCFAs were strongest among women with proximal colon cancer. No statistically significant associations were observed for BA or SCFA measures among men. Serum concentrations of BAs, particularly downstream microbial metabolites of cholic acid, were strongly associated with increased risk of CRC among women.

Food processing groups and colorectal cancer risk in Morocco: evidence from a nationally representative case-control study.

The aim of this study was to investigate the association between the consumption of foods and drinks from different food processing categories using the NOVA classification and CRC risk among Moroccan adults. 1453 cases and 1453 matched controls aged at least 18years and recruited from the 5 greater Moroccan regions were interviewed by trained investigators about their habitual diet using a standardized food frequency questionnaire (FFQ). Foods were categorized according to their degree of processing by the NOVA classification. Intakes of each food processing group were categorized into tertiles based on the distribution of controls with the lowest tertile considered as the reference category. Multivariable conditional logistic regression models were used to assess the association between each group and CRC risk (Odds Ratio (OR) and 95% Confidence Intervals (CI)), taking relevant confounders into account. High consumption of unprocessed or minimally processed foods (NOVA group 1) was significantly inversely (OR = 0.82, 95%CI = 0.72-0.93), while high consumption of ultra-processed foods and drink products (NOVA group 4) was significantly positively (OR = 1.40, 95% CI = 1.22-1.61) associated with CRC risk as compared to the lowest intake group. These results were similar for colon and rectum sub-sites. This is the first study to evaluate the association between the NOVA classification groups and CRC risk in an African country. Our results suggest that the consumption of ultra-processed foods and drink products may be associated with an increased risk of developing CRC, but longitudinal studies are needed to confirm these results.

A236 ASSOCIATION OF STOOL METABOLOMIC PROFILE AND MICROBIOME COMPOSITION RISK SCORE WITH FUTURE ONSET OF CROHN’S DISEASE

BackgroundMicrobial composition-based risk score (MRS) was recently developed and validated to predict future risk of developing Crohn’s disease (CD) among healthy first-degree relatives (FDR) of CD patients. We hypothesized that stool metabolomic profiles, some of which are linked to the gut microbiome, are associated with future risk of CD.AimsTo assess the association of stool metabolomic profile with onset of CD and to determine the correlation between stool metabolites and the MRSMethodsHealthy FDR of CD patients were recruited as part of the nested case-control cohort of the CCC-GEM Project. Healthy FDRs who later developed CD (n=56) were matched approximately 1:1 by age, sex, follow-up duration, and geographical location with control FDRs remaining healthy (n=66). Stool metabolomics were assessed using the Metabolon’s DiscoveryHD4™ platform, and the stool microbiome characterised by 16s rDNA amplicon sequencing. We fitted a multivariable conditional logistic regression model on the disease status as a function of individual stool metabolites. We additionally performed Spearman correlation between each stool metabolite and the MRS.ResultsAmong 1,029 stool metabolites that were analyzed, 79 were associated with future risk of CD (p<0.05); however, none remained significant after multiple testing correction (FDR correction). Considering the exploratory nature of this study with limited sample size, we focused on the top seven metabolites associated with CD onset (p<0.01). Of these, two stool metabolites (dimethylglycine, methylmyristate) were associated with increased risk of CD onset while five (cytosine, guanine, cytidine, hydroxyglutarate, nervonate) were associated with decreased risk of developing CD. The two metabolites positively associated with CD onset were positively correlated with the MRS, while the five metabolites negatively associated with CD onset, were negatively correlated with the MRS. Meanwhile, 24 stool metabolites had significant correlation with MRS (FDR-corrected p<0.2). Among those, a total of four stool metabolites (cytosine, guanine, methymyristate, cytidine) overlapped with the top seven stool metabolites associated with CD onset.ConclusionsStool metabolite profiles may predict future risk of CD. A subset of these metabolites have significant correlation with the MRS with consistent direction of effect. This may suggest that stool metabolites mediate the putative effect of the gut microbiome on CD risk. Further validation in the full GEM cohort is warranted.Funding AgenciesCCC, CIHRThe Leona M. and Harry B. Helmsley Charitable Trust; Kenneth Croitoru is the recipient of the Canada Research Chair in Inflammatory Bowel Diseases; Sun-Ho Lee is a recipient of the Imagine/ CIHR/CAG Fellowship Award; Sun-Ho Lee, Juan Antonio Raygoza Garay, and Williams Turpin are recipients of fellowship awards from the Department of Medicine, Mount Sinai Hospital, Toronto, Canada.