Polytomous Logistic Regression Analysis Research Articles

Associations between recalled childhood gender nonconformity and adult sexual dysfunction in Denmark: baseline assessment in the Project SEXUS cohort study.

Sexual dysfunctions may negatively affect an individual's self-perceived womanhood or manhood, but whether gender nonconformity in childhood or adolescence can influence adult sexual functioning has not been examined so far. To explore the possible link between recalled childhood gender nonconformity and sexual dysfunctions in adulthood in a large sample. We analyzed baseline questionnaire data from Project SEXUS, a nationally representative cohort study on sexual health among 15- to 89-year-old Danish citizens. Our sample included sexually active participants aged ≥18 years who were queried about gender nonconformity in childhood or adolescence (N = 21 390). To capture sexual dysfunctions, we assessed (1) difficulties with lubrication, orgasm, vaginal cramps precluding sexual intercourse, and/or genital pain during partnered sexual activity in women and (2) difficulties with erection, premature ejaculation, orgasm, and/or genital pain during partnered sexual activity in men. Furthermore, we assessed whether such difficulties were perceived as problematic. The 6-item Female Sexual Function Index and the 5-item International Index of Erectile Function served as standardized measures. Polytomous logistic regression analyses yielded demographically weighted adjusted odds ratios (aORs) with 95% CIs for associations between childhood gender nonconformity and sexual dysfunctions, controlling for age, sociodemographics, health-related factors, and other potential confounders. Sexual difficulties and dysfunctions, as well as scores on the Female Sexual Function Index and International Index of Erectile Function. Age-adjusted odds ratios indicated that sexual dysfunctions were significantly more common among childhood gender-nonconforming than conforming participants. After controlling for additional potential confounders, most sexual dysfunctions-notably, vaginal cramps in women (aOR,2.12; 95% CI, 1.25-3.60) and genital pain dysfunction in men (aOR,2.99; 95% CI, 1.79-4.99)-remained significantly increased among childhood gender-nonconforming respondents. Findings suggest that self-perceived gender nonconformity in childhood or adolescence may negatively affect sexual functioning in adult life. If confirmed by future studies, they may warrant a clinical emphasis on such issues in sexologic treatment and care. Our study is the first to report associations between childhood gender nonconformity and adult sexual dysfunction, building on data from a large-scale, nationally representative cohort study. The retrospective assessment of childhood gender nonconformity via one item might have neglected significant dimensions of this construct. The present study is the first to show that individuals who recall being gender nonconforming in childhood or adolescence may be at a greater risk of experiencing sexual dysfunctions, particularly sexual pain disorders, as adults.

Association of Polygenic Score With Tumor Molecular Subtypes in Papillary Thyroid Carcinoma.

Genome-wide association studies have identified germline variants associated with elevated PTC risk. It is also known that somatic driver mutations contribute to PTC development and as such PTCs can be further categorized into different molecular subtypes based on their somatic alterations. However, it remains unknown whether identified germline variants predictive of PTC risk are associated with specific molecular subtypes. The primary goal of the present study is to determine whether germline genetic risk, as assessed using a polygenic score (PGS) is associated with molecular subtypes of papillary thyroid carcinoma (PTC), defined based on tumor driver mutation status. This study was carried out using data from The Cancer Genome Atlas (TCGA) thyroid cancer study. A previously validated 10-single-nucleotide variation PGS for PTC derived from genome-wide association study hits was calculated to ascertain germline genetic risk. The primary molecular subtypes of interest were defined by tumor driver mutation status (BRAFV600E-mutated vs RAS-mutated vs "other"). We also explored associations between PGS and molecular subtypes defined by messenger RNA (mRNA) expression, microRNA expression, and DNA methylation patterns. Polytomous logistic regression analysis was used to assess the association between PGS and PTC molecular subtype with and without adjustment for clinical variables. Odds ratios (ORs) with their 95% CIs were estimated. A total of 359 patients were included in the study. PGS was significantly associated specific tumor molecular subtypes defined by tumor driver mutation status. Increasing germline risk was associated with having a higher odd of BRAFV600E-mutated PTC compared to PTCs without driver mutations in the "other" category. No significant difference was detected in terms of PGS tumor categorization in the RAS subtype compared to BRAFV600E. In exploratory analyses, PGS was also associated with mRNA-, microRNA-, and DNA methylation-defined molecular subtypes, as defined by the TCGA PTC study. PGS has molecular subtype-specific associations in PTC, which has implications for their use in risk prediction.

Abstract C129: Lifetime cumulative cigarette exposure and young-onset breast cancer risk by subtype in the Young Women’s Health History Study

Abstract Few studies have described the association between lifetime smoking exposures and young-onset breast cancer (YOBC) risk by BC subtypes including the human epidermal growth factor receptor 2 (HER2) subtype. This study explored associations between lifetime cumulative cigarette smoking exposure from both secondhand smoke (SHS) and personal smoking exposures and YOBC risk, overall and by BC subtype. Data are from the Young Women’s Health History Study, a population-based, case-control study of BC in non-Hispanic Black and White women 20-49 years of age. Invasive BC cases were identified in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015 (n=1,812). Controls were identified through area-based sampling and frequency matched to cases by study site, race and age (n=1,381). Lifetime cumulative cigarette exposure (LCCE) was categorized as no personal or SHS exposure, only SHS exposure in childhood, only SHS exposure in adulthood, SHS exposure in childhood & adulthood, and ever personally smoked (with or without SHS exposure). BC subtypes were defined as Luminal A, Luminal B, HER2-type, and triple negative (TN) BC. We conducted multivariable adjusted sample-weighted logistic regression analysis to estimate the association between LCCE and YOBC risk among all participants and then among women who never personally smoked by duration of SHS exposure (<15 and ≥15 years). We also conducted adjusted polytomous logistic regression analyses and the Wald test to assess heterogeneity by BC subtype. Lifetime cumulative SHS exposure only was reported by 42% of participants, and an additional 37% reported personally smoking. In adjusted models, compared to no SHS, LCCE was not significantly associated with overall YOBC risk. Suggestive differences in YOBC risk by BC subtype were observed, however (P heterogeneity=0.04), with a suggestive increased odds of HER2-type BC with ever smoking (adjusted odds ratio [aOR] 1.61; 95% confidence interval [CI] 0.91, 2.86). Among participants who never smoked, duration of childhood SHS exposure was associated with differences in YOBC risk by subtype (P heterogeneity=0.01); childhood SHS exposure of ≥15 years compared to no childhood SHS was associated with a significantly decreased odds of HER2-type BC (aOR 0.31; 95% CI 0.12, 0.83) and a suggestive increased odds of TNBC (aOR 1.43; 95% CI 0.95, 2.16) while childhood SHS exposure of <15 years compared to no childhood SHS was associated with a suggestive decreased odds of Luminal A BC (aOR 0.74; 95% CI 0.54, 1.03); the latter two findings did not reach statistical significance. Our results suggest that LCCE is associated with differences in risk of YOBC by BC subtype where personal cigarette smoking may be associated with an increased risk for HER2 type YOBC while childhood SHS exposure for ≥15 years may be associated with a decreased risk of HER2 type YOBC and an increased risk of TN YOBC. These findings warrant further examination. Citation Format: Ugonna Ihenacho, Ann S. Hamilton, Wendy J. Mack, Anna H. Wu, Jennifer B. Unger, Dorothy R. Pathak, Kelly A. Hirko, Richard T. Houang, Michael F. Press, Kendra L. Schwartz, Lydia R. Marcus, Ellen M. Velie. Lifetime cumulative cigarette exposure and young-onset breast cancer risk by subtype in the Young Women’s Health History Study [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C129.

Growth and development of children and related influencing factors: a cross-sectional study of the families with children aged 0-6 years in Jiangsu Province

To investigate the growth and development of children aged 0-6 years in Jiangsu Province of China and the effects of family factors on the children's growth and development. The stratified random sampling method was used to select 2 004 families with children aged 0-6 years of Jiangsu Province. A questionnaire survey on nutritional knowledge, attitude, and behavior was performed for the main caregivers. The Z-score method was used to evaluate nutritional status. The ordinal polytomous logistic regression analysis model was used to investigate the influencing factors for nutritional status. A total of 2 290 questionnaires were distributed, among which 2 004 valid questionnaires were collected (87.51%). The mean age of the children was (28±14) months, and there were 1 105 boys (55.14%) and 899 girls (44.86%). The primary caregivers were mostly parents (1 867 families, 93.16%), and the caregivers of 1 466 families (73.15%) had a university/college degree. Most families had an annual income of 50 000-100 000 yuan/year or 100 000-200 000 yuan/year, accounting for 32.88% and 34.23%, respectively. The results of Z-score showed the growth retardation rates of 1.45% (16/1 105) in boys and 1.78% (16/899) in girls, the underweight rates of 0.54% (6/1 105) in boys and 0.67% (6/899) in girls, the emaciation rates of 1.36% (15/1 105) in boys and 2.00% (18/899) in girls, and the obesity rates of 8.78% (97/1 105) in boys and 10.12% (91/899) in girls, respectively. The multivariate logistic regression analysis showed that a higher annual family income and a higher nutrition knowledge level of caregiver were beneficial to the growth and development of children (P<0.05). Children aged 0-6 years in Jiangsu Province have a good status of growth and development but a relatively high obesity rate, and therefore, the monitoring of obesity should be taken seriously. Family economic status and the level of nutritional knowledge of caregivers have a significant impact on children's growth and development.

Indicators Predicting Inpatient Mortality in Post-Stroke Patients Admitted to a Chronic Care Hospital: A Retrospective Pilot Study.

Evidence concerning the mortality of post-stroke patients admitted to a chronic-phase hospital seems to be lacking. This pilot study aimed to identify mortality-related clinical variables in the admission of post-stroke patients from a retrospective perspective. A group of 38 non-survival stroke patients and another group of 46 survival stroke patients in a chronic-phase ward of the single center were recruited. Clinical variables including age, sex, stroke type, and Barthel index (BI) score were collected. The difference in the age and BI scores on admission were statistically significant between the two groups (p < 0.01). Polytomous logistic regression analysis revealed that age (odds ratio = 1.09, p = 0.03, and 95% confidence interval: 1.01–1.07), male sex (odds ratio = 5.04, p = 0.01, and 95% confidence interval: 1.39–18.27), and BI scores on admission (odds ratio = 0.90, p = 0.01, and 95% confidence interval: 0.83–0.97) could be prognostic variables. The percentage of correct classification was 83.3%. Age, male sex, and BI scores on admission may be prognostic indicators. The result of this study could lay the groundwork for palliative care for such a clinical population.

Association between immunologic markers and cirrhosis in individuals with chronic hepatitis B

Host immune response and chronic inflammation associated with chronic hepatitis B virus (HBV) infection play a key role in the pathogenesis of liver diseases such as cirrhosis and hepatocellular carcinoma (HCC). We sampled 175 HCC, 117 cirrhotic and 165 non-cirrhotic controls from a prospective cohort study of chronically HBV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis vs. controls and those who developed HCC vs. cirrhosis. Leave-one-out cross validation was used to generate receiver operating characteristic curves to compare the predictive ability of marker groups. After multivariable adjustment, HGF (Q4v1OR: 3.74; p-trend = 0.0001), SLAMF1 (Q4v1OR: 4.07; p-trend = 0.0001), CSF1 (Q4v1OR: 3.00; p-trend = 0.002), uPA (Q4v1OR: 3.36; p-trend = 0.002), IL-8 (Q4v1OR: 2.83; p-trend = 0.004), and OPG (Q4v1OR: 2.44; p-trend = 0.005) were all found to be associated with cirrhosis development compared to controls; these markers predicted cirrhosis with 69% accuracy. CDA analysis identified a nine marker model capable of predicting cirrhosis development with 79% accuracy. No markers were significantly different between HCC and cirrhotic participants. In this study, we assessed immunologic markers in relation to liver disease in chronically-HBV infected individuals. While validation in required, these findings highlight the importance of immunologic processes in HBV-related cirrhosis.

Abstract 836: Immunologic markers and the progression of liver disease in HCV-positive individuals

Abstract Background: Host immune response and chronic inflammation associated with chronic hepatitis C virus (HCV) infection play a key role in the progression of liver disease from cirrhosis to hepatocellular carcinoma (HCC). We evaluated a large panel of circulating immunologic markers to better understand the natural history of HCV-related liver disease. Methods: We sampled 94 HCC, 68 cirrhotic and 100 non-cirrhotic controls from a Taiwanese prospective cohort study of chronically HCV-infected individuals. Multivariable polytomous logistic regression and canonical discriminant analysis (CDA) were used to compare baseline plasma levels for 102 markers in individuals who developed cirrhosis as compared to controls and those who developed HCC. P-values for individual markers were corrected for multiple testing using a false discovery rate of 10%; a p-value&amp;lt;0.05 was used to determine significance in CDA. Receiver operating characteristic curves were used to compare the predictive ability of marker groups from both analyses. Results: After adjusting for age, sex, years of follow-up, serum alanine aminotransferase level, alcohol and smoking, DEFA-1 (p-trend: &amp;lt;0.0001), ITGAM (p-trend: &amp;lt;0.0001), CCL18 (p-trend: 0.002) and ARTN (p-trend: 0.003) were all found to be positively associated with the development of cirrhosis when compared to non-cirrhotic controls; the same four markers were shown to be associated with HCC when compared to cirrhotic participants. Taken together, these four markers predicted cirrhosis and HCC development with 79% and 88% accuracy, respectively in adjusted models. CDA models isolated a twelve-marker signature that included DEFA1, CCL18, and ARTN, improving predictability of cirrhosis development to 91% accuracy in adjusted models. Using the same methods, a fourteen-marker signature that included DEFA-1, ITGAM, CCL18 and ARTN was found to predict HCC development with 97% accuracy when compared to cirrhotic individuals in adjusted models. Conclusion: To our knowledge, this is the first prospective study to assess immunologic markers in relation to liver disease progression in individuals chronically infected with HCV. While further validation is required, these findings highlight the importance of immunologic processes in HCV-related disease. Citation Format: Ilona Argirion, Ruth M. Pfeiffer, Zhiwei Liu, Allan Hildesheim, Ligia Pinto, Katherine A. McGlynn, Jessica L. Petrick, Tram Kim Lam, Thomas R. O'Brien, Kelly Yu, Chien-jen Chen, Hwai-I Yang, Mei-Hsuan Lee, Jill Koshiol. Immunologic markers and the progression of liver disease in HCV-positive individuals [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 836.

Associations of diet, physical activity and polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults Women\u2019s Study

BackgroundCurrent evidence supports the adoption of healthy diet and physical activity (PA) behaviors in patients with polycystic ovary syndrome (PCOS), given the positive effects of those behaviors on physical well-being. An improved understanding of the associations between diet and PA with PCOS is needed to ascertain whether tailored dietary and PA recommendations are needed for this population. Thus, we investigated the associations of diet and PA with PCOS and its isolated features.MethodsCross-sectional study. Of the 748 women who were included in this study from the Coronary Artery Risk Development in Young Adults (CARDIA) Women’s Study, 40 were classified as having PCOS, 104 had isolated hyperandrogenism (HA) and 75 had isolated oligomenorrhea (OA). Dietary intake was measured using the CARDIA diet history questionnaire and diet quality was scored using the Alternative Healthy Eating Index 2010; a higher score indicated a better quality diet. Self-reported PA was measured using a validated interviewer-administered questionnaire. Polytomous logistic regression analyses examined the associations between diet and PA with PCOS, HA, and OA status (outcomes), adjusting for age, race, total energy intake, education, and/or body mass index. The threshold for statistical significance was set at p < 0.05.ResultsMean age of the participants was 25.4 years (SD 3.6) and 46.8% of participants were Black women. There was little to no association of total energy intake, nutrients, diet quality, and PA with PCOS, HA or OA status.ConclusionEnergy intake, nutrient composition, diet quality, and PA were not associated with PCOS, supporting recent PCOS guidelines of using national recommendations for the general population to encourage health-promoting behaviors among women with PCOS. However, longitudinal studies evaluating changes in diet and physical activity in relation to the development and/or the progression of PCOS are needed to establish a causal association.

Polygenic Risk Score and Risk of Chronic Lymphocytic Leukemia, Monoclonal B-Cell Lymphocytosis (MBL), and MBL Subtypes

Background MBL is a precursor to chronic lymphocytic leukemia (CLL) and is subclassified into low-count (LC) MBL (absolute B-cell count&amp;lt;0.5x109/L) and high-count (HC) MBL (absolute B-cell count between 0.5 and 5x109/L). We previously reported that a polygenic risk score (PRS) based on a weighted average of 41 CLL-susceptibility variants was associated with risk of both MBL and CLL among a cohort of individuals from CLL families. Here we evaluate this PRS in an independent cohort of MBL and CLL individuals of European ancestry (EA), all of whom were ascertained agnostic to CLL family-history status. We also evaluate the PRS by MBL subtype (LC/HC), and in African American (AA) CLL cases and controls. Methods We genotyped 535 EA MBLs (139 HC-MBL, 396 LC-MBLs), 735 CLLs (640 EA, 95 AA), and 2,866 controls (2,631 EA, 235 AA) from the Mayo Clinic CLL Resource, Duke University, and Weill Cornell Medical College. We computed the CLL-PRS for each individual and used logistic regression to estimate odds ratios (OR) and 95% confidence intervals, adjusting for age and sex. To assess discriminatory accuracy, we computed the c-statistic. Among EA individuals, we calculated a trend test among LC-MBL, HC-MBL, and CLL risk using the P-value for heterogeneity from a polytomous logistic regression analysis. Moreover, we plotted a boxplot for the PRS among controls, LC-MBL, HC-MBL, and EA CLL, as well as for AA CLL cases and controls, and tested the statistical difference using the Kruskal Wallis test and Mann-Whitney test, respectively. Results We found a significant association of PRS with overall MBL risk (OR=1.87, P=1.1x10-28) with good discrimination (c-statistic=0.72). Significant associations were also found for LC-MBL (OR=1.75, P=7.5x10-19, c-statistic=0.72), HC-MBL (OR=2.22, P=1.4x10-17, c-statistic=0.74), and CLL of EA (OR=2.60, P=1.2x10-62, c-statistic=0.78), with a significant difference among these cohorts (Figure 1.A) and a significant positive trend across these cohorts (Pheterogeneity=8.4x10-6). Although we observed a 33% increased risk of CLL in AA (c-statistic=0.57), the PRS was borderline significant (P=0.07, Figure 1.B). Conclusion The CLL-PRS is a strong prediction-tool for risk of CLL and MBL among individuals of EA. Future studies are needed to improve the PRS for AAs including performing GWAS of AA in order to identify CLL-susceptibility SNPs that are more representative within known CLL loci and to discover novel CLL loci that are unique for AAs. Disclosures Parikh: GlaxoSmithKline: Honoraria; Janssen: Honoraria, Research Funding; Ascentage Pharma: Research Funding; AbbVie: Honoraria, Research Funding; Merck: Research Funding; TG Therapeutics: Research Funding; Genentech: Honoraria; Pharmacyclics: Honoraria, Research Funding; MorphoSys: Research Funding; AstraZeneca: Honoraria, Research Funding; Verastem Oncology: Honoraria. Braggio:DASA: Consultancy; Bayer: Other: Stock Owner; Acerta Pharma: Research Funding. Brander:Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding; MEI Pharma: Other, Research Funding; Ascentage: Other, Research Funding; ArQule: Consultancy, Other, Research Funding; NCCN: Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Pfizer: Consultancy, Other; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Novartis: Consultancy, Other; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; Tolero: Research Funding; Teva: Consultancy, Honoraria; DTRM: Other, Research Funding; BeiGene: Other, Research Funding; Novartis: Consultancy, Other; NCCN: Other; Verastem: Consultancy, Honoraria, Other, Research Funding. Cerhan:NanoString: Research Funding; BMS/Celgene: Research Funding. Kay:Astra Zeneca: Membership on an entity's Board of Directors or advisory committees; Agios Pharma: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Acerta Pharma: Research Funding; Juno Theraputics: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Cytomx: Membership on an entity's Board of Directors or advisory committees; Tolero Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyer Squib: Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Research Funding; Abbvie: Research Funding; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Dava Oncology: Membership on an entity's Board of Directors or advisory committees. Furman:Acerta: Consultancy; AstraZeneca: Consultancy, Research Funding; Beigene: Consultancy; Abbvie: Consultancy; Pharmacyclics: Consultancy; Sunesis: Consultancy; TG Therapeutics: Consultancy, Research Funding; Verastem: Consultancy; Incyte: Consultancy; Genentech: Consultancy; Janssen: Consultancy, Speakers Bureau; Loxo Oncology: Consultancy; Oncotarget: Consultancy. Shanafelt:Mayo Clinic: Patents &amp; Royalties: and other intellectual property; Genentech, Pharmacyclics LLC, an AbbVie Company, AbbVie, GlaxoSmithKline, and Merck: Research Funding.

Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies.

Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65-1.04)] but not BRAF-wildtype tumors [1.09 (0.97-1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (P trend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. SIGNIFICANCE: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.

Abstract 4652: Intake of dietary fruit, vegetables, and fiber and risk of colorectal cancer according to molecular subtypes: A pooled analysis

Abstract Background and Objectives: While there is a clear association between many lifestyle-related factors and colorectal cancer (CRC) risk, the protective associations of fruit, vegetables, and fiber intake have been shown in many, but not all epidemiological studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by CRC molecular subtypes. To explore this hypothesis, we investigated the association between fruit, vegetables, and fiber intake and four well-established CRC molecular characteristics. Methods: We analyzed 9 observational studies including 8,783 CRC cases with molecular tumor markers for microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), and somatic mutations in BRAF (V600E) and KRAS (codon 12 or 13), and 7,869 controls. We used case-only and polytomous logistic regression analyses to assess the association between dietary intake of fruit, vegetables, and fiber with CRC molecular subtypes defined by each marker separately and in combination. Results: We found that higher fruit intake was associated with a decreased risk of BRAF-mutated tumors [Odds ratio (OR) 4th vs. 1st quartile = 0.72 (95% confidence interval (CI) = 0.57-0.91)], but not with BRAF-wildtype tumor [OR 4th vs. 1st quartile = 1.01 (95%CI = 0.90-1.13); p-difference = 3e-03]. Higher fiber intake showed significant negative association with MSS/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype when using these markers separately and in combination (p-trend range from 2e-03 to 4e-05). These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated or KRAS-mutated tumors, but the differences were not statistically significant. Conclusion: Higher fruit intake may be associated with a decreased risk of BRAF-mutated CRC but not with BRAF-wildtype CRC. Additionally, higher fiber intake may be associated with a decreased risk of MSS/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors. These results may explain in part the inconsistent findings between fruit or fiber intake and overall CRC risk that have previously been reported. Citation Format: Akihisa Hidaka, Harrison A. Tabitha, Daniel D. Buchanan, Michael Hoffmeister, Marc J. Gunter, Xiaoliang Wang, Yi Lin, Wei Sun, Syed H. Zaidi, Martha L. Slattery, Bethany Van Guelpen, Steven J. Gallinger, Michael O. Woods, Mark A. Jenkins, Shuji Ogino, Polly A. Newcomb, Peter T. Campbell, Li Hsu, Ulrike Peters. Intake of dietary fruit, vegetables, and fiber and risk of colorectal cancer according to molecular subtypes: A pooled analysis [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 4652.

Combined effect of noise and hand-transmitted vibration on noise-induced hearing loss in the automobile manufacturing industry

Objective: To investigate the combined effect of noise and hand-transmitted vibration on noise-induced hearing loss (NIHL) in the automobile manufacturing industry. Methods: From September 2018 to January 2019, cluster sampling was used to select 998 workers in an automobile factory as study subjects, among whom 352 workers exposed to noise alone were enrolled as noise group, 342 workers exposed to noise and hand-transmitted vibration were enrolled as combined effect group, and 304 workers without exposure to occupational hazardous factors were enrolled as control group. A questionnaire survey and pure tone audiometry were performed for all study subjects. An analysis of variance was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; a ordinal polytomous logistic regression analysis was used to investigate the influencing factors for NIHL (with 0.05 as the inclusion criteria and 0.10 as the exclusion criteria for independent variables) . Results: There was a significant difference in L(Aeq, 8 h) between groups (P<0.05) ; the noise group and the combined effect group had a significantly higher L(Aeq, 8 h) than the control group (P<0.05) , while there was no significant difference in L(Aeq, 8 h) between the noise group and the combined effect group (P>0.05) . The control group had a significantly lower detection rate of hearing loss than the noise group and the combined effect group (P<0.0125) , and the combined effect group had a significantly higher detection rate of hearing loss than the noise group (P<0.0125) . The ordinal polytomous logistic regression analysis showed that after adjustment for confounding factors such as age, working years, sex, smoking, and drinking, both noise exposure and exposure to both noise and hand-transmitted vibration had an influence on workers' hearing (P<0.05) , and the workers exposed to both noise and hand-transmitted vibration had a higher risk of hearing loss than those exposed to noise alone. Conclusion: There may be a combined effect of noise and hand-transmitted vibration in the automobile manufacturing industry, which can increase the risk of NIHL in workers.

Endovascular aneurysm closure during out of office hours is not related to complications or outcome

PurposeA possible disadvantage of endovascular occlusion outside work hours is that complex procedures might expose patients to additional risk when performed in a suboptimal setting. In this prospective cohort study, we evaluated whether treatment during out of office hours is a risk factor for per-procedural complications and clinical outcome.MethodsWe included 471 endovascular-treated, consecutive aneurysmal subarachnoid hemorrhage patients (56.6 ± 13.1, 69% female), from two prospective observational databases which were retrospectively analyzed. Primary outcome was the occurrence of per-procedural complications. Secondary outcomes were good clinical outcome (modified ranking scale ≤ 2) and death at 6-month follow-up. We determined odds ratios (OR) with 95% confidence intervals (CI) by ordered polytomous logistic regression analysis and adjusted odds ratios (aOR) for age, World Federation of Neurosurgical Societies grade, and time to treatment.ResultsMost patients were treated during office hours (363/471; 77.1%). Treatment during out of office hours did not result in an increased risk of per-procedural complications (OR 0.85 (95% CI 0.53–1.37; p = 0.51). Patients treated during out of office hours displayed similar odds of good clinical outcome and death after 6 months (OR 1.14, 95% CI 0.68–1.97 and 1.16 95% CI 0.56–2.29, respectively) compared to patients treated during office hours.ConclusionIn our study, endovascular coil embolization during out of office hours did not expose patients to an increased risk of procedural complications or affect functional outcome after 6 months.

The Establishment of Health Records of Residents in Main Urban Areas of Chongqing: A Cross-sectional Study

Objective: To describe the current situation of health records establishment of residents in main urban areas of Chongqing, analyze its influencing factors and provide reference suggestions to promote the establishment of residents' health records, so as to narrow the gap between China and other countries. Methods: A self-designed questionnaire survey was conducted among 900 residents who had lived in nine districts of Chongqing for more than 6 months by stratified random sampling. Results: In 2018, 61.4% of the sample population in the main urban area of Chongqing had health records, while 20% didn't have health records and 18.5% were unclear about whether they had health records or not; Differences in gender, age, educational background, occupation, household registration, housing type were statistically significant for the establishment of health records (P < 0.05); Polytomous logistic regression analysis showed that gender, age, educational background, occupation, household registration were the influencing factors of the establishment of health records. Conclusion: The rate of residents in the main urban areas of Chongqing who have health records needs to be improved. It is hard to establish health records for male, low-educated and floating population. Therefore, the third-party organizations and media should play a role in promoting the establishment of health records for such populations under the leadership of government departments, in order to make contributions to narrowing the gap between China and other countries.

Factors Associated With Oncologist Discussions of the Costs of Genomic Testing and Related Treatments.

Use of genomic testing is increasing in the United States. Testing can be expensive, and not all tests and related treatments are covered by health insurance. Little is known about how often oncologists discuss costs of testing and treatment or about the factors associated with those discussions. We identified 1220 oncologists who reported discussing genomic testing with their cancer patients from the 2017 National Survey of Precision Medicine in Cancer Treatment. Multivariable polytomous logistic regression analyses were used to assess associations between oncologist and practice characteristics and the frequency of cost discussions. All statistical tests were two-sided. Among oncologists who discussed genomic testing with patients, 50.0% reported often discussing the likely costs of testing and related treatments, 26.3% reported sometimes discussing costs, and 23.7% reported never or rarely discussing costs. In adjusted analyses, oncologists with training in genomic testing or working in practices with electronic medical record alerts for genomic tests were more likely to have cost discussions sometimes (odds ratio [OR] = 2.09, 95% confidence interval [CI] = 1.19 to 3.69) or often (OR = 2.22, 95% CI = 1.30 to 3.79), respectively, compared to rarely or never. Other factors statistically significantly associated with more frequent cost discussions included treating solid tumors (rather than only hematological cancers), using next-generation sequencing gene panel tests, having higher patient volume, and working in practices with higher percentages of patients insured by Medicaid, or self-paid or uninsured. Interventions targeting modifiable oncologist and practice factors, such as training in genomic testing and use of electronic medical record alerts, may help improve cost discussions about genomic testing and related treatments.

A Case-Control Study of the Association of the Polymorphisms of MTHFR and APOE with Risk Factors and the Severity of Coronary Artery Disease

Objectives: To explore the association between single-nucleotide polymorphisms (SNPs) in MTHFR and APOE and the risk of CAD and, more importantly, the severity of CAD and the profile of serum lipids, we performed a case-control study in a Chinese Han population. Methods: A total of 1,207 cases of consecutive CAD-suspected inpatients were recruited, and 406 CAD cases and 231 non-CAD controls were enrolled for the final analysis after screening for exclusion criteria. All subjects had undergone coronary angiography, and the severity of CAD was evaluated by 2 cardiologists according to the Gensini scores. The genotypes of MTHFR and APOEwere detected using real-time PCR, and then verified by Sanger sequencing. Environmental risk factors, such as age, sex, smoking, alcohol consumption, hypertension, diabetes, dyslipidemia, and BMI were collected. Statistical analyses (the χ² test, binary logistic regression analysis, and ordinal polytomous logistic regression analysis) were performed with SPSS v16.0. Results: The genotypes ofall the subjects included in the CAD and non-CAD groups in this study were successfully detected, with an agreement of 100% with Sanger sequencing. The distributions of genotypes CT and TT at MTHFR C667T were higher in CAD cases than in non-CAD controls (OR 1.99, 95% CI 1.34–2.95; OR 1.77, 95% CI 1.18–2.67; p < 0.05), whereas genotype AC at MTHFR A1298Cwas lower in CAD cases (OR 0.71, 95% CI 0.50–1.02; p < 0.05). A significant association was observed in genotypes CT and TT at MTHFR C667T and the risk of CAD (OR 1.44, 95% CI 1.27–3.67; OR 1.56, 95% CI 0.88–2.78; p < 0.05). Both genotypes and alleles of APOE were comparable in the CAD cases and non-CAD controls (p > 0.05). The genotype TT at MTHFR C667T and ε4+ at APOE were more likely to be found in the CAD subgroup with a Gensini score ≥72 (p = 0.040 and p = 0.028, respectively). Meanwhile, in the patients with genotype TT,a higher level of serum Hcy was detected, while genotype ε4+ patients possessed higher levels of serum apolipoprotein E (ApoE) and low-density lipoprotein cholesterol (LDL-C) than other genotypes. Conclusion: This study revealed that the SNP site of MTHFR C667Tis associatedwith the risk of CAD in this Chinese Han population. In addition, the genotypes of TT in MTHFR C667T and ε4+in APOE may increase the severity of CAD, and higher Hcy, LDL-C, and ApoE levels may be involved in this pathogenic process.

Abstract P331: Unfavorable Social Factors Increased the Risk of Future Disability Subsequent to Heart Failure in Elderly Japanese Community Dwellers: The Iwate KENCO Study Group

Introduction: The risk factors that contribute to future disability after heart failure (HF) are poorly understood. The aim of this study was to determine the risk factors of future disability subsequent to HF in the general elderly population in Japan. Hypothesis: We assessed the hypothesis that unfavorable social factors after than traditional cardiovascular risk factors contribute to an increased risk for disability after HF. Methods: The subjects were community-dwelling elderly individuals aged 65 years or older without a history of cardiovascular diseases. We defined disabled subjects as individuals who had been newly certified by the long-term care insurance (LTCI) system during the observation period. HF was diagnosed according to the Framingham diagnostic criteria. After excluding subjects who received LTCI without HF (n= 2,305) and subjects who had already received LTCI prior to HF onset (n=33), we classified the remaining subjects (n= 4,644) into 3 groups: event-free (no LTCI and no HF; n= 4,548, mean age = 70.1 years at the baseline survey), no LTCI after HF (n= 52, mean age = 72.3 years) and LTCI after HF (n= 44, mean age =74.6 years). We determined the multivariate-adjusted odds ratio (OR) for having each risk factor (male gender, age (increment of years), unmarried status, less educational years (&lt;7 years), no job status, smoking, drinking, hypertension, diabetes mellitus and dyslipidemia) in the latter two groups (reference: event-free) using polytomous logistic regression analysis. Results: The median follow-up period was 10.6 years (49,133 person-years), and the median period [interquartile range] from the incidence of HF to the certification for LTCI was 1.3 [0.3- 4.7] years. Significantly associated risk factors were more advanced age (OR [95% confidence intervals]:1.18 [1.10-1.25]), unmarried status (2.29 [1.14- 4.63]), less educational years (3.36 [1.72-6.55]) and regular drinking (2.58 [1.13- 5.88]) in the group of LTC after HF, while the risk factor was more advanced age (1.08 [1.02-1.15]) in the group of no LTCI after HF. Conclusion: The results suggested that unfavorable social risk factors such as unmarried status, shorter education period and regular drinking strongly contributed to the higher risk of disability subsequent to HF, while those unfavorable risk factors did not contribute to the risk of incident HF without LTCI. Preventive measures must be taken to protect elderly individuals with unfavorable social factors from disability after HF via a multidisciplinary approach.

Understanding Suicide in Pregnant and Postpartum Women, Using the National Violent Death Reporting System Data: Are There Differences in Rural and Urban Status?

Background: Suicide rates in the United States have increased by 30% since 1999 and suicide is currently the 10th leading cause of death. Suicide has also become one of the leading causes of death in pregnant and postpartum women. The aim of this study is to examine whether rurality affects the risk of suicide in pregnant and postpartum women. Methods: This study used data from the National Violent Death Reporting System, Restricted Access Dataset (2003-2012). Bivariate and multivariate analyses were used to first describe the pregnant and postpartum population versus non-pregnant females (ages 15 - 54), who all died by suicide, and then to examine urban-rural differences. Results: Rural suicide decedents were much older, married, less likely to have had a mental health diagnosis, and more likely to use a firearm. Recent intimate partner crisis and intimate partner problems were both associated with increased odds that the suicide decedent was pregnant or postpartum in both urban and rural counties, whereas presence of job problems and report of history of suicide attempt decreased the odds that the suicide decedent was pregnant or postpartum in both urban and rural counties. Multivariable polytomous logistic regression analyses revealed differences in suicide risk factors among pregnant, postpartum and non-pregnant decedents when stratified by rural and urban status. Conclusion: Our findings suggest that pregnant and postpartum women should be screened for risk of suicide, in the clinical setting, especially if there are intimate partner problems or a crisis. With proper identification and response, suicide in pregnant and postpartum women might be decreased.

Reduced bone mineral density among HIV-infected, virologically controlled young men

Reduced bone mineral density (BMD) is a frequent comorbidity observed in people living with HIV (PLHIV). We aimed to determine the prevalence of reduced BMD and its associated factors among young PLHIV men, virologically controlled by combination antiretroviral therapy (cART). A bicentric cross-sectional study. We selected men, aged less than 50 years, treated by cART, with HIV-RNA less than 50 copies/ml. BMDs of lumbar spine and hip were measured by dual-energy X-ray absorptiometry (DXA). A Z-score at either site between -1.0 and -2.0 or -2 or less defined osteopenia or osteoporosis, respectively. Linear and polytomous logistic regression analyses were performed. Among 230 men with a median age of 43 [interquartile range (IQR), 36-47] years, BMI of 23.5 (21.3-25.3) kg/m(2) and median duration of cART of 4.2 (1.7-8.5) years, reduced BMD was diagnosed in 48.3%. In multivariate analyses, BMI decrease was associated with a risk of osteopenia [odds ratio (OR) = 1.17, P < 0.01] and osteoporosis (OR = 1.24, P < 0.01). Oestradiol levels decrease were associated with osteoporosis (OR = 1.32, P < 0.05) and lower lean mass with osteopenia (OR = 2.98, P < 0.01). There was a protective effect of the duration of cART (OR = 0.87, P < 0.01), which was even greater when the duration was more than 3 years (OR = 0.44, P = 0.02). There is a high prevalence of reduced BMD among young men, despite persistent virological control of HIV-infection. This observation raises the question of extending current recommendations for BMD assessment to PLHIV aged < 50 years for whom BMD has stabilized after cART initiation, i.e. treated for more than three years.

What factors are associated with oncologist discussions of the costs of genomic testing and related treatment?

95 Background: Use of genomic testing to inform cancer treatment is an increasingly common practice in the US. Genomic testing and related treatment can be expensive and not all tests and treatments are covered by health insurance plans. Little is known about how often physicians discuss costs of genomic testing and related treatment with their patients, nor about the physician and/or practice factors associated with those discussions. Methods: We identified 1220 oncologists who participated in the National Survey of Precision Medicine in Cancer Treatment in 2017 and reported discussing genomic testing with their patients within 12 months. Weighted percentages were used to describe the frequency of cost discussions and multivariable polytomous logistic regression analyses were used to assess associations between physician and practice characteristics and the frequency of cost discussions. Results: Among oncologists who discussed genomic testing, 50.0% reported often discussing the likely costs of testing and related treatment; 26.3% reported sometimes discussing costs; and the remaining 23.7% reported never or rarely discussing costs. In adjusted analyses, oncologists who used next-generation sequencing gene panel tests were more likely to have cost discussions with their patients often (OR = 2.3; 95% CI: 1.6,3.2) or sometimes (OR = 1.8; 95% CI: 1.2, 2.7) compared to rarely or never. Other physician and practice factors associated with more frequent cost discussions were treating solid tumors only (rather than hematologic only or both hematologic and solid tumors), training in genomic testing, and working in practices with electronic medical record (EMR) alerts for genomic tests (all p &lt; 0.05). Conclusions: Physician and practice factors are associated with discussions of the costs of genomic testing and related treatments. As professional organizations increasingly recommend discussions of costs with cancer patients, consideration of modifiable physician and practice factors, such as training in genomic testing and use of EMR alerts, may help achieve these aims.