Catherine Metayer, Logan G Spector, Michael E Scheurer, Soyoung Jeon, Rodney J Scott, Masatoshi Takagi, Jacqueline Clavel, Atsushi Manabe, Xiaomei Ma, Elleni M Hailu, Philip J Lupo, Kevin Y Urayama, Audrey Bonaventure, Motohiro Kato, Aline Meirhaeghe, Charleston W K Chiang, Libby M Morimoto, Joseph L Wiemels
{"title":"Folate Metabolism and Risk of Childhood Acute Lymphoblastic Leukemia: A Genetic Pathway Analysis from the Childhood Cancer and Leukemia International Consortium.","authors":"Catherine Metayer, Logan G Spector, Michael E Scheurer, Soyoung Jeon, Rodney J Scott, Masatoshi Takagi, Jacqueline Clavel, Atsushi Manabe, Xiaomei Ma, Elleni M Hailu, Philip J Lupo, Kevin Y Urayama, Audrey Bonaventure, Motohiro Kato, Aline Meirhaeghe, Charleston W K Chiang, Libby M Morimoto, Joseph L Wiemels","doi":"10.1158/1055-9965.EPI-24-0189","DOIUrl":"10.1158/1055-9965.EPI-24-0189","url":null,"abstract":"<p><strong>Background: </strong>Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.</p><p><strong>Methods: </strong>We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software.</p><p><strong>Results: </strong>None of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni P-value of 5 × 10-6 and less-stringent P-value of 3.5 × 10-5 accounting for the number of \"independent\" SNPs). None of the 10 top (nonsignificant) SNPs and corresponding genes overlapped across ancestry groups.</p><p><strong>Conclusions: </strong>This large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups.</p><p><strong>Impact: </strong>Genetic variants in the folate pathway alone do not appear to substantially influence childhood acute lymphoblastic leukemia risk. Other mechanisms such as gene-folate interaction, DNA methylation, or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":" ","pages":"1248-1252"},"PeriodicalIF":4.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141431486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanqing Zhang, Minghao He, Peng Zhang, Yang Gao, Ling Ouyang, Xianjun He, Na Han, Jinfeng Zhang, Mengshan Guan, Yueqi Feng, Yonghua Li
{"title":"Long-Term Risks of Cardiovascular Death among Older Patients with Major Hematological Malignancies: A Population-Based Cohort Study from SEER Database.","authors":"Hanqing Zhang, Minghao He, Peng Zhang, Yang Gao, Ling Ouyang, Xianjun He, Na Han, Jinfeng Zhang, Mengshan Guan, Yueqi Feng, Yonghua Li","doi":"10.1158/1055-9965.EPI-23-1635","DOIUrl":"10.1158/1055-9965.EPI-23-1635","url":null,"abstract":"<p><strong>Background: </strong>The objective of this study was to identify the risk of cardiovascular disease (CVD)-related death in older patients with major hematological malignancies (HM).</p><p><strong>Methods: </strong>This study included 103,102 older patients diagnosed with seven major types of HM between 1975 and 2018 (median follow-up: 2.7 years) from the Surveillance, Epidemiology, and End Result database. The proportion of deaths, Fine-Gray subdistribution hazards regression model, standardized mortality ratios (SMR), and absolute excess risk (AER) were used to evaluate the risk of CVD-related death.</p><p><strong>Results: </strong>For older patients with HM, CVD-related death ranked as the second leading cause of death, surpassed only by primary malignancy. Compared to the general older population, older patients with HM had higher SMR and AER of CVD-related deaths (SMR: 1.16-1.81; AER: 41.24-308.99), heart disease-related deaths (SMR: 1.19-1.90; AER: 39.23-274.69), and cerebrovascular disease-related deaths (SMR: 0.99-1.66; AER: -0.35 to 24.15). The proportion of deaths and cumulative mortality increased with the passage of survival time, especially in patients with Hodgkin lymphoma with stage I/II and those aged ≥85 years with chronic lymphocytic leukemia, surpassing primary malignancy. The risk of CVD-related death varied among different HM types.</p><p><strong>Conclusions: </strong>For older patients with HM, long-term cardiovascular risk management needs to be focused on while addressing the primary malignancy.</p><p><strong>Impact: </strong>Our results emphasize the need to manage long-term cardiovascular risk in older patients with hematological malignancies, especially in those identified as high-risk cases.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":" ","pages":"1167-1176"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pablo S Monterroso, Kristin Knight, Michelle A Roesler, Jeannette M Sample, Jenny N Poynter
{"title":"Remote Field Application of Digital Technology for Hearing Assessments in a Cohort of Pediatric Germ Cell Tumor Survivors.","authors":"Pablo S Monterroso, Kristin Knight, Michelle A Roesler, Jeannette M Sample, Jenny N Poynter","doi":"10.1158/1055-9965.EPI-24-0203","DOIUrl":"10.1158/1055-9965.EPI-24-0203","url":null,"abstract":"<p><strong>Background: </strong>Childhood cancer survivors treated with platinum-based chemotherapy are at risk of treatment-induced hearing loss. Accurate evaluation of hearing thresholds has historically been limited to clinical audiometry, which is logistically challenging and expensive to include in epidemiologic studies. We evaluated the feasibility of using a remote, tablet-based hearing assessment in a cohort of pediatric germ cell tumor survivors treated with platinum-based chemotherapy.</p><p><strong>Methods: </strong>Survivors from the GCT Outcomes and Late effects Data (GOLD) study were recruited to the pilot study (n = 100). Study personnel conducted remote hearing assessments of standard and extended high frequency thresholds using validated tablet-based audiometry (SHOEBOX, Inc.). T tests and Wilcoxon rank-sum tests evaluated differences in assessment characteristics between children and adults. Agreement between self-reported and measured hearing loss was calculated using Cohen κ.</p><p><strong>Results: </strong>We were able to reach 136/168 (81%) eligible participants, of which 100 (74%) agreed to participate. Successful completion of the remote hearing assessment was high [97%; 20 children (ages 7-17), 77 adults (ages 18-31)]. The mean assessment length was 37.6 minutes, and the mean turnaround time was 8.3 days. We observed hearing loss at standard frequencies in 21% of participants. Agreement between self-reported and measured hearing loss was significant (P value = 1.41 × 10-7), with 83.5% concordance.</p><p><strong>Conclusions: </strong>Hearing loss measured using the remote assessment aligns with self-reporting and rates of hearing loss reported in the literature for this population.</p><p><strong>Impact: </strong>Remote application of tablet-based audiometry is a feasible and efficacious method for measuring hearing in epidemiologic studies with participants spread across large geographic areas.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":" ","pages":"1177-1184"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Guan, Colleen M McBride, Jingsong Zhao, Rebecca D Pentz, Cam Escoffery, Yuan Liu, Yichun Cao, Weihua An, James A Shepperd, Kevin C Ward
{"title":"Testing a Population-Based Outreach Intervention for Ovarian Cancer Survivors to Encourage their Close Relatives to Consider Genetic Counseling.","authors":"Yue Guan, Colleen M McBride, Jingsong Zhao, Rebecca D Pentz, Cam Escoffery, Yuan Liu, Yichun Cao, Weihua An, James A Shepperd, Kevin C Ward","doi":"10.1158/1055-9965.EPI-24-0147","DOIUrl":"10.1158/1055-9965.EPI-24-0147","url":null,"abstract":"<p><strong>Background: </strong>Most relatives of women with ovarian cancer are unaware of their increased risk for cancer and their eligibility for genetic counseling. State cancer registries offer a platform to communicate about inherited risk to this population.</p><p><strong>Methods: </strong>We conducted a two-arm randomized trial to test a theory-based communication intervention-Your Family Connects (YFC)-compared to the standard Georgia Cancer Registry (GCR) contact. A total of 1,938 eligible ovarian cancer survivors were randomly assigned to either the YFC arm (n = 969) or the Standard Care arm (n = 969). We assessed the number of ovarian cancer survivors and their close relatives who logged on to the study website by arm.</p><p><strong>Results: </strong>Survivor reach was significantly higher in the Standard Care arm than YFC (20.8% vs. 15.2%, respectively; P < 0.001). However, reach to relatives was limited to listed relatives in the YFC arm (n = 20, 13.2%), with little participation from those in the Standard Care arm (n = 1, 0.4%). Pooling across arms, minority race, longer time since diagnosis, and older age were all significantly associated with a decreased likelihood that the survivor accessed the website.</p><p><strong>Conclusions: </strong>The YFC intervention showed lower effectiveness for engaging survivors but was more effective than Standard Care in engaging at-risk relatives. Other factors (e.g., time since diagnosis) associated with lower reach must be considered in refining future outreach approaches.</p><p><strong>Impact: </strong>Partnering with a state cancer registry to foster family communication about inherited cancer risk is feasible but the possibility for broad population reach warrants further testing.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":" ","pages":"1185-1193"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniel W Cramer, Allison F Vitonis, Raina N Fichorova, Hidemi S Yamamoto, Francesmary Mudugno, Olivera J Finn
{"title":"Variables Affecting CA15.3 Tumor Antigen Expression and Antibodies against It in Female National Health and Nutritional Survey Participants.","authors":"Daniel W Cramer, Allison F Vitonis, Raina N Fichorova, Hidemi S Yamamoto, Francesmary Mudugno, Olivera J Finn","doi":"10.1158/1055-9965.EPI-24-0187","DOIUrl":"10.1158/1055-9965.EPI-24-0187","url":null,"abstract":"<p><strong>Background: </strong>Cancers of ductal origin often express glycoprotein mucin 1 (MUC1), also known as CA15.3, with higher levels leading to poor prognosis. Conversely, anti-MUC1 antibodies develop in some patients, leading to better prognosis. We sought to identify epidemiologic factors associated with CA15.3 antigen or antibody levels.</p><p><strong>Methods: </strong>Levels of CA15.3 antigen and anti-CA15.3 IgG antibodies were measured in archived sera from 2,302 mostly healthy women from the National Health and Nutritional Survey; and epidemiologic predictors of their levels were examined using multivariate and correlational analyses.</p><p><strong>Results: </strong>Among racial groups, Black women had the highest levels of CA15.3 antigen and lowest levels of antibodies. Increasing body mass index and current smoking were associated with low anti-CA15.3 antibody levels. Low CA15.3 antigen levels were seen in oral contraceptive users and high levels in women who were pregnant or lactating at the time of blood collection, with the latter group also having high antibody levels. Past reproductive events associated with high antigen levels included the following: later age at menarche, having given birth, and history of endometriosis. Lower antigen levels were seen with increasing duration of OC use. Anti-CA15.3 antibody levels decreased with an increasing estimated number of ovulatory years.</p><p><strong>Conclusions: </strong>Key determinants of CA.15.3 antigen or antibody levels include the following: race, body mass index, smoking, later menarche, childbirth, number of ovulatory cycles, and endometriosis.</p><p><strong>Impact: </strong>This study supports the premise that known epidemiologic factors affecting risk for or survival after MUC1-expressing cancers may, at least partially, operate through their association with CA15.3 antigen or antibody levels.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":" ","pages":"1211-1219"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Searching for the Scale-Able Weight Loss Intervention: Can One Size Fit All? Lessons to Be Learned from the EQUAL Trial.","authors":"Travis R Moore, Wendy Demark-Wahnefried","doi":"10.1158/1055-9965.EPI-24-0735","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-24-0735","url":null,"abstract":"<p><p>Overweight and obesity affect 71.2% of adults in the United States, with cancer survivors not far behind at 70.3%. Subgroups such as those diagnosed with acute lymphoblastic leukemia (ALL) face even greater challenges. The Exercise and Quality Diet after Leukemia (EQUAL) trial sought to address weight management issues among ALL survivors by implementing a remotely delivered weight loss intervention, leveraging the previously proven Practice-based Opportunities for Weight Reduction (POWER) program. Despite a strong foundation and design, the EQUAL trial yielded null results. Key differences in study populations and intervention contexts between the EQUAL and POWER trials, such as the lack of primary care physician involvement in EQUAL, contributed to these outcomes. EQUAL's failure to meet its accrual target and poor adherence among participants highlighted challenges in engaging this unique population. Contrary to EQUAL's conclusions, evidence from other studies supports the efficacy of remote interventions for weight loss among cancer survivors. The lack of qualitative assessment among ALL survivors and key integration to inform intervention adaptations undermined EQUAL's impact. However, EQUAL's impressive retention rate offers valuable insights. Lessons from EQUAL underscore the need for well-fitted, remotely delivered interventions and the importance of thoughtfully adapted and tailored approaches to specific survivor populations. See related article by Fiedmann et al., p. 1158.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":"33 9","pages":"1147-1149"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Theodore M Brasky, Leah R Jager, Alison M Newton, Xilin Li, Holli A Loomans-Kropp, John L Hays, Karen L Margolis, Juhua Luo
{"title":"Use of Nonsteroidal Anti-Inflammatory Drugs and Pancreatic Cancer Risk in the Women's Health Initiative.","authors":"Theodore M Brasky, Leah R Jager, Alison M Newton, Xilin Li, Holli A Loomans-Kropp, John L Hays, Karen L Margolis, Juhua Luo","doi":"10.1158/1055-9965.EPI-24-0305","DOIUrl":"10.1158/1055-9965.EPI-24-0305","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is among the most fatal human cancers and the fourth leading cause of cancer death in the United States. Evidence suggests that chronic inflammation may play a role in pancreatic carcinogenesis and its inhibition through nonsteroidal anti-inflammatory drugs (NSAID) may reduce pancreatic cancer incidence.</p><p><strong>Methods: </strong>We examined associations of total and individual NSAIDs with pancreatic cancer risk among postmenopausal women participating in the Women's Health Initiative observational study and clinical trial cohorts. Among 117,452 women, aged 55 to 79 years, 727 incident pancreatic cancer cases were reported over 18 years of follow-up. Cox regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for associations between NSAIDs and pancreatic cancer risk.</p><p><strong>Results: </strong>Relative to non-use, consistent use of any NSAID was inversely associated with pancreatic cancer risk (HR 0.71, 95% CI, 0.59-0.87), primarily driven by strong associations for aspirin use (HR 0.67, 95% CI, 0.52-0.86). Use of total or individual non-aspirin NSAIDs was not associated with pancreatic cancer. Upon stratified analysis, we observed stronger associations for NSAIDs among participants with prevalent diabetes (HR 0.28, 95% CI, 0.10-0.75) relative to those without (HR 0.75, 95% CI, 0.61-0.92; P-interaction = 0.03).</p><p><strong>Conclusions: </strong>Additional large prospective studies with careful measurement of NSAID type, dose, and frequency are needed to further investigate the possibility of added benefit among individuals diagnosed with diabetes.</p><p><strong>Impact: </strong>This study adds to existing evidence from prospective studies and clinical trials suggesting that use of aspirin may provide moderate benefit for pancreatic cancer prevention.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":" ","pages":"1203-1210"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yingye Zheng, Paul D Wagner, Amit G Singal, Samir M Hanash, Sudhir Srivastava, Ying Huang, Ying-Qi Zhao, Suresh T Chari, Guillermo Marquez, Ruth Etizioni, Tracey L Marsh, Ziding Feng
{"title":"Designing Rigorous and Efficient Clinical Utility Studies for Early Detection Biomarkers.","authors":"Yingye Zheng, Paul D Wagner, Amit G Singal, Samir M Hanash, Sudhir Srivastava, Ying Huang, Ying-Qi Zhao, Suresh T Chari, Guillermo Marquez, Ruth Etizioni, Tracey L Marsh, Ziding Feng","doi":"10.1158/1055-9965.EPI-23-1594","DOIUrl":"10.1158/1055-9965.EPI-23-1594","url":null,"abstract":"<p><p>Before implementing a biomarker in routine clinical care, it must demonstrate clinical utility by leading to clinical actions that positively affect patient-relevant outcomes. Randomly controlled early detection utility trials, especially those targeting mortality endpoint, are challenging due to their high costs and prolonged duration. Special design considerations are required to determine the clinical utility of early detection assays. This commentary reports on discussions among the National Cancer Institute's Early Detection Research Network investigators, outlining the recommended process for carrying out single-organ biomarker-driven clinical utility studies. We present the early detection utility studies in the context of phased biomarker development. We describe aspects of the studies related to the features of biomarker tests, the clinical context of endpoints, the performance criteria for later phase evaluation, and study size. We discuss novel adaptive design approaches for improving the efficiency and practicality of clinical utility trials. We recommend using multiple strategies, including adopting real-world evidence, emulated trials, and mathematical modeling to circumvent the challenges in conducting early detection utility trials.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":"33 9","pages":"1150-1157"},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristen D Brantley, Regina G Ziegler, Neal E Craft, Susan E Hankinson, A Heather Eliassen
{"title":"Circulating Estrogen Metabolites and Risk of Breast Cancer among Postmenopausal Women in the Nurses' Health Study.","authors":"Kristen D Brantley, Regina G Ziegler, Neal E Craft, Susan E Hankinson, A Heather Eliassen","doi":"10.1158/1055-9965.EPI-24-0577","DOIUrl":"https://doi.org/10.1158/1055-9965.EPI-24-0577","url":null,"abstract":"<p><strong>Background: </strong>Estradiol and estrone are well-established risk factors for postmenopausal breast cancer (BC). Experimental evidence suggests that specific estrogen metabolites, produced via irreversible hydroxylation of estrone and estradiol at the 2- or 16-position may independently influence carcinogenesis.</p><p><strong>Methods: </strong>We performed a nested case-control study of BC (328 BC cases; 639 controls) among postmenopausal women within the Nurses' Health Study (NHS)to examine the role of estrogens and estrogen metabolites (jointly referred to as EM). Plasma concentrations of each EM (unconjugated+conjugated forms) were measured by liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression, adjusting for BC risk factors, estimated relative risks (RR) and 95% confidence intervals (CI) of BC across quintiles of individual EM, EM pathways, and pathway ratios. Associations by estrogen/progesterone receptor (ER/PR) status were analyzed by unconditional logistic regression.</p><p><strong>Results: </strong>Estradiol and estrone were strongly associated with increased BC risk [estradiol: RRQ5v.Q1 (95% CI)=2.64 (1.64-4.26), estrone: 2.78 (1.74-4.45); both p-trends<0.001]. The 2-hydroxylation pathway was strongly associated with risk [RRQ5v.Q1=3.09 (1.81-5.27), p-trend<0.001], and remained so after adjusting for unconjugated estradiol [RRQ5v.Q1=2.23 (1.25-3.96), p-trend=0.01]. While the 16-hydroxylation pathway was modestly associated with risk [RRQ5v.Q1=1.62 (1.03-2.54), p-trend=0.01], the association was attenuated after unconjugated estradiol adjustment [RRQ5v.Q1=1.24 (0.77-1.99), p-trend=0.19]. Similar positive associations with the 2-pathway and 16-pathway were observed for ER+/PR+ and ER-/PR- tumors.</p><p><strong>Conclusions: </strong>In this cohort of postmenopausal women, 2-hydroxylation of estrone and estradiol was associated with increased BC risk, independent of unconjugated estradiol.</p><p><strong>Impact: </strong>These results highlight the need to revisit the role of estrogen metabolism in BC etiology and prevention.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyle D Klingbeil, Dustin L Dillon, Erfan Zarrinkhoo, Kirollos Bechay, Joon Y Park, Jordan M Rook, Michael A Mederos, Mark D Girgis, Keren Chen, Kuan-Ting Chen, Roshan Bastani, Shawdi Manouchehr-Pour, Priyanka Dubé, Karoly Viragh, Mariam Thomas, Victor Chiu, Brian E Kadera
{"title":"Hispanic/Latino Ethnicity is an Independent Predictor of Worse Survival for Gastric Cancer in a Multicenter Safety-Net Patient Population.","authors":"Kyle D Klingbeil, Dustin L Dillon, Erfan Zarrinkhoo, Kirollos Bechay, Joon Y Park, Jordan M Rook, Michael A Mederos, Mark D Girgis, Keren Chen, Kuan-Ting Chen, Roshan Bastani, Shawdi Manouchehr-Pour, Priyanka Dubé, Karoly Viragh, Mariam Thomas, Victor Chiu, Brian E Kadera","doi":"10.1158/1055-9965.EPI-23-1224","DOIUrl":"10.1158/1055-9965.EPI-23-1224","url":null,"abstract":"<p><strong>Background: </strong>Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients.</p><p><strong>Methods: </strong>We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016 to December 31, 2020 within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model.</p><p><strong>Results: </strong>448 patients who received care from five medical centers were included. 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs 60.7 years, p <0.01), demonstrate higher state area deprivation index (6.4 vs 5.0, p <0.01), and present with metastatic disease (59.8% vs 45%, p =0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival (HR 1.56, [95% CI 1.06-2.28], p = 0.02).</p><p><strong>Conclusions: </strong>Hispanic patients treated within a large, multi-center safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors.</p><p><strong>Impact: </strong>Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}