Distinct Risk Factor Profiles Research Articles

Young hearts at risk: Unveiling novel factors in myocardial infarction susceptibility and prevention

ABSTRACT The increasing incidence of acute myocardial infarction (AMI) among the young population represents a significant and emerging health concern, contributing substantially to both mortality and morbidity. Unlike myocardial infarctions occurring in older individuals, traditional risk factors such as diabetes and hypertension exhibit a weaker association in the younger demographic. Consequently, there is a pressing need for a deeper understanding of novel risk factors that contribute to AMI in young patients. In this review, we explore distinct risk factor profiles associated with young-onset AMI in comparison to older patients. Special attention is given to novel risk factors, examining their susceptibility factors and exploring preventive measures. The comprehensive risk profile of extremely young South Asians who develop early coronary arterial disease is not yet fully understood. There are many novel evolving risk factors associated with young AMI which need intervention to reduce morbidity and mortality. It has been seen that established inflammatory markers like lipoprotein (a), dyslipidaemia, long COVID, and new emerging risk factors like air pollution (micro- and nanoplastics), periodontitis, acute stress, energy drinks, misuse of recreational drugs may increase risk and influence treatment, and outcomes of AMI in this young population. Screening of emerging novel risk markers and their optimization is important in preventing young patients with AMI. The role of conventional risk factors should not be overlooked and should be treated aggressively. Sex and geographic-specific base approaches are required to reduce risk factors and prevent AMI in young. More prospective studies are needed to evaluate the increasing incidence of young AMI and its associated novel risk factors.

Epidemiological profile of stroke in Qatar: Insights from a seven-year observational study

ObjectivesStroke prevalence is progressively increasing in developing countries due to increased vascular risk factors. This study aims to describe the epidemiology, prevalent risk factors, and outcomes of stroke in a multi-ethnic society of Qatar. Materials and MethodsWe conducted a retrospective analysis of all patients with suspected stroke admitted to stroke services between January 2014 and September 2020. ResultsA total of 11,892 patients were admitted during this period with suspected stroke. Of these, the diagnosis was ischemic stroke (48.8 %), transient ischemic attack (10.3 %), intracerebral hemorrhage (10.9 %), cerebral venous sinus thrombosis (1.3 %), and stroke mimics (28.6 %). The median age was 52 (43–62), with a male–female ratio of 3:1. The study population was predominantly Asian (56.8 %) and Arab (36 %). The majority of the patients were hypertensive (66.8 %), diabetic (47.9 %), and dyslipidemic (45.9 %). A history of prior stroke was observed in 11.7 %, while 0.9 % had prior transient ischemic attack. Among ischemic strokes, 31.7 % arrived within 4.5 h, 12.5 % received thrombolysis, and 4.6 % underwent thrombectomy. Median Door-to-Needle time was 51 (33–72) minutes. The average length of stay was 5.2 ± 9.0 days, with 71.5 % discharged home, 13.8 % transferred to rehabilitation, 9.3 % to other specialties, 3 % to long-term care, and 2.4 % suffered in-hospital mortality. ConclusionStroke in Qatar is characterized by a younger, expatriate-dominant cohort, with notable prevalence of ischemic and hemorrhagic stroke and a distinct risk factor profile. Further analysis of epidemiological differences among different population groups can inform targeted policies for prevention and management to reduce the burden of disease.

Incidence and survival of second primary non-Hodgkin lymphoma: A Surveillance, Epidemiology, and End Results-based cohort study.

The aim of this study was to investigate patient survival and factors associated with survival in second primary non-Hodgkin lymphoma (NHL) compared with the first primary NHL. The retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Demographic characteristics, histological types, Ann Arbor stage, and treatment information were collected. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with overall survival (OS) and cancer-specific survival (CSS) in the first and second primary NHLs. Of 318,168 cases followed for 5 years, 299,248 patients developed the first primary NHL and 18,920 patients developed the second primary NHL. This study identified a rising incidence of first and second primary NHL from 2000 to 2014. For the second primary NHL, the OS risk was higher when compared to the first primary NHL (HR: 1.13, 95% CI: 1.11 to 1.15, P <0.001). Risk factors that negatively affected OS in the first primary NHL included being male, over 40 years of age, certain marital statuses, specific histological types, and advanced disease stages. In contrast, being of White race and having histological types such as Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and mantle B-cell NHL were associated with better OS outcomes. Treatments like surgery, radiation therapy, and chemotherapy were associated with a lower risk of OS and CSS in the first primary NHL. For the second primary NHL, the detrimental risk factors were similar but also included being over the age of 60. Certain histological types showed a lower OS risk relative to diffuse Large B-cell Lymphoma (DLBCL). While surgery and chemotherapy were beneficial for OS, radiation therapy did not improve survival in second primary NHL cases. Notably, undergoing chemotherapy for the first primary cancer increased the OS risk in the second primary NHL, whereas surgery and radiation seemed to offer a protective effect against OS risk in the second primary NHL (all P <0.05). Our findings emphasize the need for tailored strategies in managing the second primary NHL, given the distinct survival patterns and risk factor profiles compared to the first primary NHL. Future research should aim to further elucidate these differences to improve prognosis and treatment approaches for second primary NHL patients.

The unique risk factor profile of triple negative breast cancer: a comprehensive meta-analysis.

Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. This systematic review and meta-analysis examines whether known risk factors for breast cancer are also associated with TNBC in adult females. EMBASE, Medline, SCOPUS, and grey literature were queried with no limit on the date or language of publication. The exposures of interest included parity, breastfeeding, duration of breastfeeding, age at menarche, age at first live birth, oral contraceptive (OC) use, duration of OC use, use of menopausal hormone therapy (MHT), family history, body mass index (BMI), alcohol use, smoking and breast density. The main outcome of interest was TNBC. Study quality was determined using the Newcastle-Ottawa scale for case control studies and cohort studies. We estimated weighted odds ratios from random effects models to study the exposure-outcome associations. Protocol was registered under the number: PROSPERO 2021 CRD42021254594. Thirty-three studies were included. Family history, longer duration of oral contraceptive use, and higher breast density were significantly associated with increased risk for TNBC, whereas, later age at menarche, later age at first birth and breastfeeding were protective against TNBC. Parity, MHT, alcohol, smoking, and BMI were not significantly associated with TNBC overall, but higher parity was associated with higher risk among Black women. Our findings highlight that TNBC has a distinct risk-factor profile compared to overall breast cancer. This can be the foundational work in identification of actionable TNBC risk factors to improve prevention and early detection of these poor prognosis breast tumors.

A Multi-Step Precision Pathway for Predicting Allograft Survival in Heterogeneous Cohorts of Kidney Transplant Recipients.

Accurate prediction of allograft survival after kidney transplantation allows early identification of at-risk recipients for adverse outcomes and initiation of preventive interventions to optimize post-transplant care. Many prediction algorithms do not model cohort heterogeneity and may lead to inaccurate assessment of longer-term graft outcomes among minority groups. Using data from a national Australian kidney transplant cohort (2008-2017) as the derivation set, we developed P-Cube, a multi-step precision prediction pathway model for predicting overall graft survival in three ethnic subgroups: European Australians, Asian Australians and Aboriginal and Torres Strait Islander Peoples. The concordance index for the European Australians, Asian Australians, and Aboriginal and Torres Strait Islander Peoples subpopulations were 0.99 (0.98-0.99), 0.93 (0.92-0.94) and 0.92 (0.91-0.93), respectively. Similar findings were observed when validating P-cube using an external dataset [Scientific Registry of Transplant Recipient Registry (2006-2020)]. Six sub-categories of recipients with distinct risk factor profiles were identified. Some factors such as blood group compatibility were considered important across the entire transplant population. Other factors such as human leukocyte antigen (HLA)-DR mismatches were unique to older recipients. The P-cube model identifies allograft survival specific risk factors within a heterogenous population and offers personalized survival predictions in a diverse cohort.

Abstract 4205: Profiling symptom burden of RAS and BRAF mutations in patients with colorectal cancer: Results from the ColoCare Study

Abstract Background: Colorectal cancer (CRC) is a complex and heterogeneous disease characterized by distinct molecular features such as RAS and BRAF mutations. Assessing these molecular aberrations provides clinical guidance for selecting and predicting response with therapeutic modalities. Few reports have suggested that patient symptom burden at diagnosis differs across molecular subtypes of CRC. However, the association of RAS and BRAF mutations and symptom burden post-diagnosis in CRC patients has yet to be examined in a prospective cohort. Methods: We assessed CRC patients, stage I-IV, enrolled in the Moffitt ColoCare Study site with clinical molecular testing results and who completed a six-month questionnaire. Tumor mutation (MT) status (RAS/BRAF/Wildtype (WT)) was abstracted from the medical record. The MD Anderson Symptom Inventory (MDASI) was used to assess the severity of 13 cancer-related symptoms on a 1-to-10 scale. Mean scores in mutation subgroups were compared with one-way ANOVA. Linear regression analysis evaluated the association between symptom burden and mutation status. Multivariable regression models were adjusted for age, sex, stage at diagnosis, treatment, and microsatellite instability (MSI). Results: Among the 158 patients, the mean age at diagnosis was 60.9 ± 11.58 years. The prevalence of RAS and BRAF mutations was 30.4% (N=48) and 6.3% (N=10), respectively. Statistically significant mean differences between the mutation subgroups were distress (p=0.005), difficulty remembering (p=0.015), lack of appetite (p=0.042), and sadness (p=0.007). Patients with a BRAF-MT reported significantly more distress (p=0.001), difficulty remembering (p=0.029), and sadness (p=0.002) at six months compared to RAS-MT or RAS/BRAF-WT. Patients with a RAS-MT reported an increased lack of appetite (p=0.038) compared to BRAF-MT or RAS/BRAF-WT. Patients with a BRAF-MT reported higher severity of symptoms interfering with the enjoyment of life (p&amp;lt;0.001), work (p=0.005), and mood (p&amp;lt;0.001) compared to RAS-MT or RAS/BRAF-WT. In an adjusted multivariable model, patients with BRAF-MT tumors reported significantly greater distress compared with RAS/BRAF-WT patients [β = 3.18 per unit increase in severity, 95% CI (1.30 - 5.07), p=0.001)]. Overall symptom burden was associated with greater interference with daily activities for BRAF-MT patients when compared to RAS/BRAF-WT patients [β = 2.95, 95% CI (1.42 - 4.48), p&amp;lt;0.001)]. Conclusions: Tumors with BRAF-MT are molecularly classified into the serrated pathway, which has distinct clinical characteristics and risk factor profile. In this study, patients with tumors harboring BRAF-MT reported a higher symptom burden six months post-diagnosis than those with RAS-MT or RAS/BRAF-WT tumors. While the prevalence of BRAF-MT was low in this population, these findings warrant further investigation in a larger cohort. Citation Format: Gazelle Rouhani, Amanda M. Bloomer, Maria F. Gomez, Gillian K. Trujillo, Devon N. Conant, Seth I. Felder, Cornelia M. Ulrich, Christopher I. Li, Jane C. Figueiredo, Adetunji T. Toriola, Biljana Gigic, Martin Schneider, David Shibata, Erin M. Siegel. Profiling symptom burden of RAS and BRAF mutations in patients with colorectal cancer: Results from the ColoCare Study. [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 4205.

Waitlist and posttransplantation outcomes of lean individuals with nonalcoholic fatty liver disease.

Lean individuals with nonalcoholic fatty liver disease (NAFLD) represent a subset of patients with a distinct risk factor profile. We assessed the association between body mass index (BMI) on waitlist and postliver transplantation (LT) outcomes among these patients. We retrospectively analyzed the United Network for Organ Sharing data, including adult patients with NAFLD listed for LT between February 27, 2002, and June 30, 2020. We first used competing risk analyses to estimate the association of BMI with waitlist removal due to death or clinical deterioration. We then conducted Kaplan-Meier estimates and Cox regression models to determine the impact of weight change during the waiting list on all-cause mortality and graft failure after LT. Patients with normal weight (BMI 18.5-24.9 kg/m 2 ) suffered higher waitlist removal (adjusted subdistribution hazard ratio 1.26, 95% confidence interval [CI] 1.10-1.43; p =0.001) compared with patients with obesity class I (BMI 30-34.9 kg/m 2 ). Those who remained at normal weight had higher all-cause mortality (adjusted hazard ratio [aHR] 1.61, 95% CI 1.32-1.96; p <0.001) and graft failure (aHR 1.57, 95% CI 1.32-1.88; p <0.001) than patients with stable obesity. Among patients with normal weight, those with the greatest weight increase (BMI gain ≥3 kg/m 2 ) had lower all-cause mortality (aHR 0.55, 95% CI 0.33-0.93; p =0.03) and graft failure (aHR 0.49, 95% CI 0.30-0.81; p =0.01) compared with patients with stable weight (BMI change ≤1 kg/m 2 ). Patients with NAFLD with normal weight have increased waitlist removal and those who remained at normal weight during the waitlist period have worse posttransplantation outcomes. Identifying and addressing factors influencing apparent healthy weight prior to LT are crucial to mitigate poor outcomes.

Risk factors for extremely preterm and very preterm birth

Aim. To evaluate the prevalence of preterm birth and risk factors for extremely preterm, very preterm, and moderate to late preterm birth.Materials and Methods. We retrospectively assessed case histories of 11,500 pregnant women delivered in Kuzbass Regional Children's Clinical Hospital during 2019-2021 and their newborns. Among the studied factors were gestational age, birth weight, sex, 5-minute Apgar score, maternal age (&lt; 20 years, 20-35 years, ≥ 35 years), parity (primiparity or multiparity), active smoking, maternal diseases during pregnancy (gestational hypertension, intrahepatic cholestasis of pregnancy, gestational diabetes mellitus, anemia, gastrointestinal and genitourinary diseases), chorioamnionitis, and pregnancy complications (placental abruption, placenta previa, vaginal bleeding, polyhydramnios), fetal distress, and fetal growth restriction.Results. Prevalence of preterm birth was 8.4%. The potential risk factors for preterm birth were placental abruption, placenta previa, short (&lt; 25 mm) cervix, intrahepatic cholestasis of pregnancy, gestational hypertension, chorioamnionitis, anemia, young (&lt; 20 years) and advanced (≥ 35 years) maternal age, primiparity, active smoking, and fetal distress. Among them, placental abruption, placenta previa, short (&lt; 25 mm) cervix, gestational hypertension, and chorioamnionitis were specific risk factors of extremely preterm and very preterm birth whilst intrahepatic cholestasis of pregnancy was the risk factor of moderate to late preterm birth.Conclusion. Extremely preterm, very preterm, and moderate to late preterm birth have distinct risk factor profiles, highlighting the need for differential pregnancy management strategies.

Distinct Reproductive Risk Profiles for Intrinsic-Like Breast Cancer Subtypes: Pooled Analysis of Population-Based Studies.

Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear. Analyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided. Compared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like. This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

Abstract 2254: Risk models for lung cancer in never-smoking women in Shanghai with implications for screening

Abstract Background: The majority of female lung cancer cases in Asia are never-smokers with distinct risk factor profiles. Given the high burden of disease in this population, there is an increasing need to improve the understanding of lung cancer. Current risk models for lung cancer focus on active smokers and individuals of European ancestry. Therefore, we developed statistical models by integrating genetic and environmental risk factors to estimate absolute and population attribute risk of lung cancer among never-smoking women in Asia. Methods: We built absolute risk models for lung cancer among never-smoking women using data from 71,300 women (760 incident cases) in the Shanghai Women’s Health Study (SWHS), a population-based prospective cohort study. Relative risks were estimated using a multivariable Cox regression model with questionnaire-based risk factors. To account for missing genetic data for some subjects, we simulated genotypes for 10 common single nucleotide polymorphisms (SNP) using information on minor allele frequencies (MAF) and odds ratio estimates from previous genome-wide association studies (GWAS), conditional on family history of lung cancer. We used the iCARE tool to build two models for predicting lifetime (40 years) and 6-year absolute risk of lung cancer using age-specific lung cancer incidence rates, age-specific competing mortality rates, and risk factor distribution with: 1) questionnaire-based risk factors only and 2) questionnaire and genetic data. We then used the full absolute risk model to estimate the population attributable risk (PAR) due to modifiable risk factors, namely coal use and exposure to environmental tobacco smoke (ETS). Results: The questionnaire-based only model included family history of lung cancer, coal use, exposure to ETS, and body mass index (BMI). The full model also included data on 10 lung cancer related SNPs from our previous GWAS and had a wider spread in distribution of absolute lifetime risk (median=2.41%; range=0.43-12.36) compared to the questionnaire-based only model (median=2.72%; range=1.93-4.87). We used the full model to estimate the PAR and found that 1.74% and 6.33% of lung cancer cases could be prevented if never-smoking women in Shanghai did not use coal and were not exposed to ETS, respectively. Furthermore, we found that the full model estimated that 2.5% of the study population had a 6-year absolute risk of lung cancer higher than 1.51%, which is the suggested risk threshold for screening by existing risk models. Conclusion: We built risk models for never-smoking Asian women and estimated the contribution of coal use and ETS to the burden of lung cancer in Shanghai. This initial work shows promise for expanding and validating risk models in this population with potential translational implications, such as providing insight to identifying high risk individuals that may be eligible for lung cancer screening and primary prevention efforts. Citation Format: Batel Blechter, Parichoy Pal Choudhury, Xiao-ou Shu, Wei Zheng, Qiuyin Cai, Gong Yang, Jason Y.Y. Wong, Bu-Tian Ji, Wei Hu, Anne Rositch, Nilanjan Chatterjee, Nathaniel Rothman, Qing Lan. Risk models for lung cancer in never-smoking women in Shanghai with implications for screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2254.

Donor Screening for Fecal Microbiota Transplantation in China: Evaluation of 8483 Candidates

Donor Screening for Fecal Microbiota Transplantation in China: Evaluation of 8483 Candidates

Comorbid anxiety and depression, depression, and anxiety in comparison in multi-ethnic community of west China: prevalence, metabolic profile, and related factors

ObjectivesTo identify the prevalence, lifestyle factors, chronic disease status, and assessing the metabolic profile, comparing key differences in a cohort of subjects aged at least 50 years old among depression combined anxiety, depression and anxiety in a multi-ethnic population in west China. MethodsA large multi-ethnic sample of 6838 participants aged 50 years old (mean age 62.4 ± 8.3 years) from West China Health and Aging Trend (WCHAT) study was analyzed. We categorized all participants into four groups: (a) comorbid anxiety and depression symptomology (CAD), (b) anxiety only, (c) depression only, or (d) neither depression nor anxiety. Different variables like anthropometry measures, life styles, chronic disease and blood test were collected. Depressive symptoms were assessed using the 15‐item Geriatric Depression Scale (GDS-15). GDS‐15 scores ≥5 indicate depression. Anxiety status was assessed using Generalized Anxiety Disorder (GAD-7) instrument and the scores ≥5 was considered as having anxiety. Different variables like anthropometry measures, life styles, cognitive function and chronic disease comorbidities were collected and serum parameters were tested. Multivariable logistic regression adjusted for age, sex, and ethnicity was done to compare between those with the mental outcomes and without.Results: The proportions of CAD, anxiety and depression were 9.0%, 12.8% and 10.6% respectively with ethnic diversity. The 'comorbid' group shown greater frequency of being female, having a lower educational level, higher prevalence of being single/divorced/widowed, drinking alcohol and smoking, more chronic disease profile and cognitive decline compared with individuals with only one disorder. And the metabolic profile showed differences in albumin, total protein, creatinine, uric acid, thyroid hormones in comparing CAD symptomology and the 'neither symptomology'. ConclusionsYi, Qiang and Uyghur ethnic groups have a higher prevalence of mental disease compared with Han in west China. And these mental disease had a distinct risk factor profile in age, sex, educational level, chronic disease and cognitive function. Vitamin D levels were lower among those with mental disease compared to those without.

Prevalence and Risk Factors of Cerebral Microbleeds: Analysis From the UK Biobank.

To determine the prevalence of and risk factors for cerebral microbleeds (CMBs) at different locations in a large healthy community population. A total of 8,159 participants from the UK Biobank with MRI scans suitable for CMB analysis were included. Brain susceptibility-weighted imaging data were acquired on 2 identical 3.0T scanners. The Microbleed Anatomical Rating Scale was used to identify definite CMBs. Generalized linear models were used to determine independent associations with all CMBs and lobar, deep, and infratentorial CMBs. The mean age at scan was 62.1 ± 7.4 years. One or more definite CMBs were detected in 572 (7.0%) participants. Of those with CMBs, 439 (76.7%) had lobar CMBs, 103 (18.0%) had deep CMBs, and 83 (14.5%) had infratentorial CMBs. Age was an independent risk factor for CMBs in all locations. APOE4 and male sex were positively associated and higher body mass index was negatively associated with lobar CMBs. Hypertension, smoking, and alcohol consumption were associated with deep CMBs, but not with lobar CMBs. Only age was associated with infratentorial CMBs. The associations were unchanged after controlling for white matter hyperintensity lesion volume as a marker of small vessel disease severity. In this large population-based study, CMB prevalence detected using a low sensitivity and high specificity system was 7%. There were distinct risk factor profiles for CMBs in lobar and deep locations consistent with different underlying pathophysiologic processes. Clinical Trial registration number: UK Biobank application number 19463.

Independent association of marijuana use and poor oral hygiene with HPV-negative but not HPV-positive head and neck squamous cell carcinomas.

Sexual behavior is associated with human papillomavirus (HPV)-positive head and neck cancer, whereas tobacco and alcohol use are associated with HPV-negative cancer. A case-control study was designed to investigate additional demographic and behavioral factors independently associated with these distinct oral cancers. From 2011 to 2014, 249 newly diagnosed oral cavity and oropharyngeal squamous cell carcinoma (OSCC) cases were matched (1:2) on age, gender, and self-identified race to 498 controls without a cancer history attending the outpatient otolaryngology clinic at The Ohio State University in Columbus. Cases were stratified by detection of high-risk HPV DNA and RNA in tumors. Demographic and behavioral data were collected using an audio computer-assisted self-interview, and associations with HPV-positive versus HPV-negative OSCCs were investigated by use of univariable and multivariable conditional logistic regression models. After adjustment for oral sexual behavior, the odds of HPV-positive cancer decreased with the patient's years of education. Annual income, tobacco smoking, alcohol drinking, marijuana smoking, and poor oral hygiene were not associated with HPV-positive OSCC. In contrast, the odds of HPV-negative OSCC increased independently with decreased annual income, decreased with a high number of marijuana hit-years, and increased with fewer than annual dental visits after adjustment for lifetime tobacco and alcohol use. Sexual behavior and education were not associated with HPV-negative OSCC. The distinct risk-factor profiles for HPV-positive and HPV-negative OSCC are confirmed and extended in this case-control study, thus supporting 2 principal etiological pathways for OSCC development. Sexually acquired human papillomavirus (HPV) infection is an established cause of tonsil and base of tongue cancers. This study compared and contrasted risk factors for HPV-positive and HPV-negative oral cancers. Low number of years of education and sexual behavior are associated with HPV-positive cancer. In contrast, low annual income, infrequent dental visits, and tobacco and alcohol use are associated with HPV-negative cancers. Long-term marijuana use appears protective for HPV-negative cancer. Public health efforts to address these modifiable risk factors may prevent oral cancer.

Lower Extremity Revascularization for Chronic Limb-Threatening Ischemia among Patients at the Extremes of Age

Patients with chronic limb-threatening ischemia (CLTI) at the extremes of age are thought to have distinct risk factor profiles and poor outcomes after lower extremity revascularization (LER). The aim of this study is to examine the relationships among age, risk factor profiles, and outcomes of LER in patients with CLTI in a large database focusing on the extreme age groups. Patients undergoing LER for CLTI in the Vascular Quality Initiative suprainguinal bypass, infrainguinal bypass, and peripheral vascular intervention files were reviewed through 2019. Patients were stratified into 3 groups: premature peripheral artery disease (PAD) (≤50years old), 51-84years old, and elderly (≥85 years old). Trends in major amputation and mortality by age group were analyzed. There were 156,513 patients who underwent LER for CLTI. Of these, 9,063 (5.79%) patients had premature PAD, 131,694 (84.14%) patients were 51-84years old, and 15,756 (10.07%) were elderly. Patients with premature PAD were more likely to have insulin-dependent diabetes, be dialysis-dependent, and be active smokers compared to patients 51-84years old and the elderly. Elderly patients were more likely to undergo an endovascular procedure for tissue loss compared to younger groups. Perioperative and 1-year major amputation rates were highest among patients with premature PAD and decreased with increasing age (P<0.001), while perioperative and 1-year mortality increased with age (P<0.001). On multivariable analysis, premature PAD was associated with an increased risk of major amputation (odds ratio, OR=1.41 [1.22-1.62]), while elderly age was associated with decreased odds of major amputation compared to patients 51-84years old (OR=0.61 [0.51-0.73]). Patients at the extremes of age have significantly different outcomes after LER for CLTI. Although mortality increases with age, the risk of major amputation decreases. Patients with premature PAD constitute a group of patients with a high risk of perioperative and 1-year major amputation.

Lower Extremity Revascularization Among Patients at the Extremes of Age With Chronic Limb-Threatening Ischemia

Patients presenting with chronic limb-threatening ischemia (CLTI) at the extremes of age are thought to have distinct risk factor profiles and poor outcomes after lower extremity revascularization (LER). The aim of this study is to examine the relationship of age with the risk factor profile and outcomes of LER in patients with CLTI in a large database focusing on the extreme age groups.

Abstract C075: Association of obesity with breast cancer subtypes among non-Hispanic Black women

Abstract Although non-Hispanic White and non-Hispanic Black women have similar breast cancer incidence rates, Black women are more likely to be diagnosed with aggressive or late-stage disease and have higher mortality rates compared to White women. Clinical studies have demonstrated that tumors lacking estrogen receptor (ER), progesterone receptor (PR) and/or human epidermal growth factor receptor 2 (HER2) (referred to as “triple negative breast cancers” or TNBC), are associated with an aggressive pathology and poor prognosis and distinct risk factor profiles, compared to those with receptor positivity. Through the current study, we examined the effect of obesity in the development of breast cancer subtypes; specifically, ER- tumors and TNBC. To examine the association between body mass index (BMI) and breast cancer subtype, we utilized a pooled dataset of Black women with breast cancer from four studies: Black Women Etiology and Survival of Triple-negative Breast Cancers Study, Southern Community Cohort Study, Nashville Breast Health Study and the Tri-State Breast Study. For all four studies, information on tumor ER, PR and HER2 status was abstracted from state cancer registry records and supplemented by available pathology reports and medical records. We calculated BMI as kg/m2, based on self-reported weight and height, and classified it as normal (18.5-&amp;lt;25), overweight (25-&amp;lt;30), obese I (30-&amp;lt;35), obese II (35-&amp;lt;40) and obese III (40+). Case-only logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between obesity and breast cancer subtype, using ER+ as the reference group for ER- and TNBC. Since the association between obesity and breast cancer has been shown to differ between pre- and postmenopausal women, all analyses were stratified by menopausal status at breast cancer diagnosis. Approximately 70% of the 2,801 women included in the study were postmenopausal at breast cancer diagnosis. Overall, 69% of the tumors were ER+, with similar proportions among pre- and post-menopausal women. In total, 25% were TNBC, of which a third were among pre-menopausal patients. In multivariable analyses, using premenopausal women with ER+ breast cancer as the reference group, those with ER- breast cancer (OR 2.16, 95% CI 1.20-3.88) or TNBC (OR 2.13, 95% CI 1.06-4.28) were more likely to be in the obese II category. Among postmenopausal women, there was no clear association between obesity and breast cancer subtype, although the obese class I category was non-significantly associated with lower risk of TNBC compared to ER+ subtype (OR 0.79, 95% CI 0.53-1.17). Our study represents one of the largest studies to assess the differential impact of obesity on breast cancer subtypes among Black women. Our findings suggest that higher BMI is associated with increased risk of TNBC for premenopausal women and demonstrates that premenopausal obese Black women are more likely to be diagnosed with ER- and TNBC compared with ER+ tumors. Citation Format: Jaleesa Moore, Maureen Sanderson, Tuya Pal, Mary Kay Fadden, Steffie-Ann Dujon, Sonya Reid, Anne Tezak, Loren Lipworth. Association of obesity with breast cancer subtypes among non-Hispanic Black women [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C075.

727 Distinct Risk Factor Profile in Young Patients With First Episode of ACS; a 14-year Registry Data Analysis

727 Distinct Risk Factor Profile in Young Patients With First Episode of ACS; a 14-year Registry Data Analysis

Abstract TP157: Ethnic Difference in Stroke Recurrence for Patients With Intracranial Atherosclerotic Stenosis

Background: Intracranial atherosclerotic stenosis (ICAS), one of most common stroke subtypes worldwide, carries high risk of stroke recurrence despite maximal medical treatment. ICAS more commonly affects non-white populations including Asian, African-American and Hispanic individuals. It is plausible that non-white stroke patients with ICAS might also have more active disease, and thus higher risks of stroke recurrence. We aim to compare the rate of stroke recurrence in stroke patients with ICAS in white and non-white population. Method: We retrospectively reviewed a consecutive series of patients with ischemic stroke due to ICAS in major vessels (MCA, ACA, PCA, intracranial segment of ICA and VA, BA) with &gt;50% stenosis identified on MRA or CTA. The clinical characteristics, risk factors and rate of stroke recurrence were compared in white and non-white patients, using Chi-square (for categorical variables) test and t-test (for continuous variables). Results: A total of 183 patients [66.3% non-white, mean (SD) age, 63 (±14) years] who were hospitalized between January 2005 and December 2010 and satisfied the inclusion criteria were included in the analysis. Compared with white patients, non-white patients had a higher rate of HTN, DM and drug abuse (Table 1), as well a nonsignificantly higher stroke recurrence rate (3 months: OR 1.29, 95% CI 0.59-2.82; long term: OR 1.63, 95% CI 0.84 - 3.18). History of CKD was the only factor associated with 3-month stroke recurrence (OR 3.73, 965 CI 1.13-12.31). Conclusion: White and non-white ischemic stroke patients with ICAS have distinct risk factor profiles and possibly distinct stroke recurrence rates. Analysis with a larger sample size is ongoing to verify this finding.

Abstract WP238: Race-Ethnic in Stroke Type and Outcome Among Hyperacute Cerebrovascular Disease Patients

Background: Prior studies have suggested race-ethnic differences in functional outcome, mortality, and use of comfort care after stroke, but have been limited by analysis of single stroke subtypes, lack of 3-month outcomes, and uncertainty whether delayed access to acute care was moderating response patterns. Methods: We analyzed all patients with final diagnoses of acute cerebral ischemia or intracranial hemorrhage enrolled within 2 hours of onset in the multicenter, prehospital NIH FAST-MAG trial. Self- or family-reported race-ethnicity was analyzed for relation to presenting stroke features, stroke subtype, and 3-month outcome. Results: Among 1616 hyperacute cerebrovascular disease patients (76.4% acute cerebral ischemia, 23.6% intracranial hemorrhage), race-ethnic frequencies were: white, non-Hispanic (W) - 55.5%, Hispanic (H) - 23.1%, Black (B) - 13.6%, Asian (A) - 8.4%. Ischemic vs hemorrhagic stroke differed by race-ethnicity, with hemorrhagic strokes more common in Hispanics (34.0%) and Asians (28.1%), compared with Whites (19.8%) and Blacks (17.8%), p = 0.0001. Age at time of stroke was highest in Whites (mean 73.1), vs H (65.5), B (63.5), A (66.9); and presenting severity (NIHSS) highest in A (mean 13.5) and H (12.7), vs W (10.7) and B (10.8). A greater dimorphic spread in 3 month outcomes was seen in W than in the other race-ethnic groups: Whites had more excellent (mRS 0-1) 3 month outcomes - W- 42.2%, B- 35.0%, H -28.4%, A-28.0%, p = 0.002; but Whites also had higher mortality by 3m - W-18.2%, A- 15.6%, H-13.0%, B-10.6%, p = 0.007. The race-ethnic difference in mortality was driven by hemorrhagic rather than ischemic strokes: ICH mortality - W-41.7%, A-19.4%, H-19.0%, B-18.2%; IS mortality: A-14.4%, W-13.5%, H-10.5%, B-9.4%. Conclusions: In this multicenter study of acute cerebrovascular disease in a diverse US region, notable race-ethnic differences included higher frequencies of hemorrhagic vs ischemic stroke among Hispanics and Asians; and more excellent, but also more fatal, 3 month outcomes among Whites. These patterns likely distinct different race-ethnic risk factor profiles shaping incident stroke type, as well as divergent sociocultural influences upon robust rehabilitation care and comfort care measures.