Epidemiology, Lifestyle, and Genetics最新文献

{"title":"Abstract A35: An integrative model of cancer disparities based on the calcium molecular theory of carcinogenesis","authors":"Bernard Kadio, S. Yaya, A. Basak, J. Gomes, K. Djé, C. Mésenge","doi":"10.1158/1538-7755.DISP17-A35","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-A35","url":null,"abstract":"One key question that comes to mind regarding cancer patterns is what factors account for the differentiated distribution of different cancer types in a given population? In other words, why is prostate cancer, for example, more prevalent among African Americans than in Caucasian Americans? Or why do native Eastern Asians record the highest incidence of gastric cancer worldwide? Beyond the commonly accepted genetic polymorphism to cancer vulnerability, this study is an in-depth exploration of the factors underpinning cancer distribution. Using a population health approach, an ecologic analysis was conducted, based on the current knowledge on the most prevalent cancer types. The calcium molecular theory of carcinogenesis, as published in our earlier work and presented at the Paris 2016 World Cancer Congress, served as basis for the analysis. As a result, cancer distribution appears to be shaped by a complex interaction between some key socioecologic determinants. Most importantly, we established that these determinants have a differentiated impact on intracellular calcium concentrations and trafficking. Thus, specific populations will be selectively vulnerable to a certain cancer type through a distinctive effect of their socioecologic characteristics on internal calcium. We conclude that calcium ion, already known as a cellular messenger, is also an environmental messenger. That molecule mediates the effects of external factors and their cellular responses, and this interaction accounts for cancer type distribution in the population at large. The work is published in two complementary papers: the first relates to cancer determinants while the second will discuss their impact on calcium metabolism. Note: This abstract was not presented at the conference. Citation Format: Bernard KADIO, Sanni Hashimi Yaya, Ajoy Basak, James Gomes, Koffi Dje, Christian Mesenge. An integrative model of cancer disparities based on the calcium molecular theory of carcinogenesis [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A35.","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116684053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A32: Trends in cause of death among Puerto Rican and United States multiple myeloma patients","authors":"Maira A. Castañeda-Avila, K. Ortiz-Ortiz, Carlos R. Torres-Cintrón, M. Epstein","doi":"10.1158/1538-7755.DISP17-A32","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-A32","url":null,"abstract":"Background/objective: Multiple myeloma (MM) is an incurable, yet treatable, cancer of plasma cells. Due to recent improvements in treatment, people diagnosed with MM have been living longer, and other comorbid conditions may be of increasing importance. This study examines temporal trends in specific causes of death among MM patients in Puerto Rico (PR) and the United States (U.S.). Methods: We analyzed primary cause of death among all incident MM cancer cases recorded in the Puerto Rico Central Cancer Registry (PRCCR) (n=3,018) and the US Surveillance, Epidemiology, and End Results Program (SEER) (n=67,733) between 1987-2013, overall and by follow-up time, age, and sex. We calculated the cumulative incidence of death due to seven selected causes and analyzed age-adjusted mortality trends by MM and other causes using joinpoint regression. Results: MM accounted for 71.7% and 71.3% of all reported deaths in PR and the U.S., respectively, among people diagnosed with MM. In PR, the proportion of patients who died from MM decreased with increasing follow-up time since diagnosis (72.3% of deaths with ≤2 years vs 65.6% with >5 years of follow-up) and the proportion of patients who died from circulatory (4.6% vs 9.0%) and respiratory system (3.7% vs 5.0%) diseases increased slightly. A similar trend of decreasing MM deaths with follow-up time was observed in the U.S. (73.2% of deaths with ≤2 years vs 66.5% with >5 years of follow-up). Joinpoint regression showed a decreasing trend in MM mortality in the U.S. and PR. Conclusion: In both PR and the U.S., people diagnosed with MM are still more likely to die from MM than from another cause. However, a decrease in MM mortality is evident, particularly in more recent years, but this decrease is lower in Puerto Rico. Citation Format: Maira A. Castaneda-Avila, Karen J. Ortiz-Ortiz, Carlos R. Torres-Cintron, Mara M. Epstein. Trends in cause of death among Puerto Rican and United States multiple myeloma patients [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A32.","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126981844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A02: Investigating the association between social disorganization, health-related quality of life (HRQL), and prostate cancer diagnoses in African American Men","authors":"C. Rodgers, S. Zenk, Karriem S. Watson, R. Winn, Rupert Evans, Catherine H Balthazar, I. Chukwudozie","doi":"10.1158/1538-7755.DISP17-A02","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-A02","url":null,"abstract":"This proposed population-based study initiated by the Early Stage Investigator from a collaborative National Cancer Institute (NCI) P20 grant between Governors State University and the University of Illinois at Chicago attempts to identify the influence of social disorganization on health-related quality of life (HRQL) in African American men living in south suburban Cook County in Illinois with prostate cancer diagnosis using the International Classification of Functioning, Disability and Health (ICF) to measure and map disability by zip code using the Geographic Information System (GIS). Although the diagnosis is 65% higher for African American men in the U.S, the relationship between prostate cancer diagnosis, health-related quality of life (HRQL), and social disorganization has not been fully examined. Pertinent experimental procedures proposed to examine this relationship include using U.S census data to obtain geographical characteristics of socially disorganized communities within south suburban Cook County in Illinois, assessing cases of prostate cancer diagnosis for African American men living in the parameters of the research, examining HRQL for these cases using ICF classifications, spatially mapping these prostate cases to determine SD, and completing a regression analysis based on HRQL and SD scores. Currently, prostate cancer is the number one cancer among all men in Illinois with 42,773 identified cases between 2002 and 2006 for all races (IDPH, Illinois Cancer Registry, 2008). Additionally, African American men living in Cook County have the highest rate for all racial groups at 227.1 per 100,000 between 2002 and 2006 (IDPH, Illinois Cancer Registry, 2008). More importantly, African American men tend to have fewer prostate-specific antigen (PSA) tests, increasing the risk for latent diagnosis and lower survival rates. These proposed data hypothesized that social disorganization might increase risk for prostate cancer rates and lower HRQL based on socioeconomic and environmental influences identified in the ICF. The proposed research attempts to identify preventable risk factors that would assist in the development of preventative care for men at risk for prostate cancer, and increasing the HRQL of African American men with a current diagnosis of prostate cancer. Citation Format: Carolyn D. Rodgers, Shannon Zenk, Karriem S. Watson, Robert Winn, Rupert Evans, Sr., Catherine Balthazar, Ifeanyi Beverly Chukwudozie. Investigating the association between social disorganization, health-related quality of life (HRQL), and prostate cancer diagnoses in African American Men [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A02.","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114793378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract C47: Obesity enhances tumor colonization and promotes expression of the spliced variant MBD2_v2 and splicing factor SRSF2 in triple-negative breast cancer","authors":"E. Girsch, G. Dyson, C. Mitrea, B. Bao, L. Polin, Aliccia Bollig-Fischer","doi":"10.1158/1538-7755.DISP17-C47","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-C47","url":null,"abstract":"Introduction: Triple-negative breast cancer (TNBC) is a molecular subtype that accounts for approximately 15-20% of invasive breast cancer diagnoses in the United States. TNBC occurs more prevalently in premenopausal African American women (AAW), and obesity coupled with chronic inflammation is a risk factor for both incidence and recurrence. TNBC is lacking therapeutic options and persons diagnosed with TNBC have the lowest 5-year survival rates among all breast cancer patients, with AAW disproportionally bearing this burden. In order to improve TNBC patient outcomes, etiologic factors driving disparities in disease progression need to be better understood. We previously showed in TNBC cell cultures that intrinsic oncogenic redox signaling promotes self-renewal capacity of cancer stem-like cells (CSC) by maintaining expression of an epigenetic reader protein and mRNA spliced variant, methyl binding domain protein 2 variant 2 (MBD2_v2). We hypothesized that obesity-induced chronic inflammation in vivo could promote a similar cancer phenotype. Methods: To study this potential phenomenon, we developed and characterized a diet-induced obesity mouse tumor xenograft (MTX) model of TNBC in C57BL/6J Rag1 (-/-) mice, a strain that maintains a functional innate immune system, to recapitulate the proinflammatory environment induced by increased adiposity. TNBC cell lines MDA-MB-468 and MDA-MB-231 were used to generate ectopic tumor xenografts in this model. Tumor colonization and growth were measured over 150 days. RT-PCR and microarray based assays were used to detect transcriptional changes in TNBC MTXs. Results: At 5 weeks post-diet consumption, mice fed a high-fat diet displayed a 5-10% increase in body weight and increased blood glucose concentration. By the end of the study high-fat fed mice displayed a 33-43% increase in body weight and appeared to have greater central adiposity post-mortem. In overweight mice relative to healthy weight controls, TNBC cell line tumor colonization rate and MBD2_v2 expression were significantly higher. Furthermore, staining for CSC marker EpCam was greater in overweight versus control MTXs, indicating that CSC self-renewal capacity could have been enhanced. Upon global gene expression analysis of overweight MTXs, we observed a significant upregulation of stem-related factors based on fold-change expression, as well as functional enrichment for RNA splicing, including SRSF2, a splicing factor that has been shown to drive MBD2_v2 expression in pluripotent stem cells. Knockdown of SRSF2 led to decreased expression of MBD2_v2 in MDA-MB-468 cells, and decreased CSC self-renewal capacity in vitro. Conclusions: Altogether these data support MBD2_v2 regulation by redox signaling, which may be driven by a proinflammatory environment in the presence of increased adiposity. Future studies will be conducted to confirm MBD2_v29s importance in obesity-related tumor colonization in in vivo overexpression and knockdown studies, and t","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124774543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A41: Social determinants of hepatocellular carcinoma in Louisiana","authors":"D. Danos, T. Ferguson, Neal Simonsen, C. Leonardi, Q. Yu, Xiao-Cheng Wu, R. Scribner","doi":"10.1158/1538-7755.DISP17-A41","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-A41","url":null,"abstract":"Purpose: Over the past three decades, hepatocellular carcinoma (HCC) is one of the few cancers for which incidence has increased in the United States (U.S.). While chronic infection with hepatitis C virus is a leading risk factor for HCC, other known risks that are more prevalent in the U.S. population, including alcohol abuse, metabolic disease, and obesity, have also contributed to increasing rates. There is growing recognition that social and/or nutritive stress represent exposures that negatively affect individual health. These factors are believed to be socially determined by conditions in an individual9s neighborhood environment. We designed a population-based study to identify potential social determinants of the increase in HCC by investigating the association of HCC incidence with neighborhood environments characterized by concentrated disadvantage. Methods: Data from the Louisiana Tumor Registry, a participant of the National Cancer Institute9s Surveillance and Epidemiology End Results (SEER) program, were used in the analysis of primary HCC diagnosed from 2008 to 2012. Cases were geocoded to census tract of residence by address at the time of diagnosis. Average annual incidence rates were calculated for age, race, and sex groups within census tracts based on 2010 US Census data. Neighborhood concentrated disadvantage index (CDI) for each census tract was calculated in accordance with the PhenX Toolkit protocol. We excluded census tracts outside of metropolitan statistical areas, as well as any tract with less than 500 people or zero households, from the analyses. Multilevel log-binomial models were used to evaluate neighborhood variation and quantify the degree of association of CDI with HCC incidence. Results: The study included 1,407 cases of HCC diagnosed from 2008 to 2012. Univariate analyses indicated significantly greater incidence of HCC among males (p Discussion/Conclusion: We have found neighborhood concentrated disadvantage to be a significant risk factor for the development of HCC. We also determined that differential exposure to neighborhoods of concentrated disadvantage contributed to observed racial disparities in HCC in Louisiana. Our results suggest that increasing rates of HCC, and existing racial disparities in the disease, are partially driven by social contexts of adverse living environments. Citation Format: Denise M. Danos, Tekeda F. Ferguson, Neal Simonsen, Claudia Leonardi, Qingzhao Yu, Xiao-Cheng Wu, Richard Scribner. Social determinants of hepatocellular carcinoma in Louisiana [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A41.","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114606737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A58: Racial disparities in head and neck cancers in an urban hospital","authors":"C. Zeigler-Johnson, S. Keith, F. Guiles, D. Cognetti, V. Bar-ad, R. Axelrod","doi":"10.1158/1538-7755.DISP17-A58","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-A58","url":null,"abstract":"Introduction: Although head and neck cancer incidence rates are higher for white residents in Philadelphia, PA, related mortality rates are highest for black residents. It is not clear how clinical factors and risk factors like HPV and smoking contribute to these disparities. The goal of this study is to determine which factors are associated with advanced head and neck cancers in a diverse sample of patients from a Philadelphia hospital. Methods: Cancer registry data from Thomas Jefferson University (957 beds, Philadelphia, PA) were used to obtain clinical records from 922 head and neck cancer patients diagnosed from 2011-2015. One patient of other race was removed from these analyses. We examined advanced cancer among the primary racial groups represented in our hospital population. Chi-square tests were used to examine differences in categorical variables. The Kruskal-Wallis test was used to compare continuous variables. Logistic and Cox regression models were designed to examine independent associations with advanced disease and time to mortality. Covariates included age, race, tumor stage, HPV status, smoking status, gender, and treatment type. Results: Our sample included 921 patients (788 white, 96 black, 37 Asian). Our descriptive analysis showed that among the three groups, blacks were more likely to be female (p=0.033). Positive HPV status was most prevalent for white patients (p=0.004). Oral and nasopharyngeal cancers were most common among Asians, and oropharyngeal cancers were most common among whites. In univariate analysis, black patients were most likely to die from their cancer. Multivariable analyses showed that current smoking (compared to never smoking) was associated with T3/T4 stage at diagnosis (OR=6.85, 95% CI=1.11-42.2). Time to death was significantly shorter for older individuals (HR=1.02 95% CI=1.01-1.05), current smokers (HR=2.24, 95% CI=1.25-4.00) and patients receiving radiation only (HR=7.70, 95% CI=1.38-42.95). Positive HPV status was protective (HR=0.29, 95% CI=0.19-0.44). No significant race effects were observed in these models. Conclusions: The results of this study suggest that race is not independently associated with head and neck cancer or associated mortality. These results also suggest that some risk factors for head and neck cancer and related outcomes may be modified by educational and behavioral interventions. Citation Format: Charnita Zeigler-Johnson, Scott Keith, Frances Guiles, David Cognetti, Voichita Bar-Ad, Rita Axelrod. Racial disparities in head and neck cancers in an urban hospital [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A58.","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115243539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A53: Plasma glucocorticogenic activity differs by race/ethnicity and alcohol intake among San Francisco Bay Area women","authors":"R. D. L. Rosa, S. Sanchez, P. Tachachartvanich, Heather Ruiz, S. Gomez, E. John, Martyn T. Smith, L. Fejerman","doi":"10.1158/1538-7755.DISP17-A53","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-A53","url":null,"abstract":"Breast cancer mortality is higher among non-Hispanic Black (NHB) and Hispanic women than non-Hispanic White (NHW) women in the United States. While various sociodemographic and lifestyle factors contribute to racial/ethnic disparities in breast cancer, the biologic processes underlying these associations remain poorly understood. Cortisol, the predominant endogenous glucocorticoid present in humans, is secreted in a diurnal pattern with the highest concentration occurring shortly after waking followed by a steady decline throughout the day. A flattened diurnal cortisol pattern (e.g., due to lower morning and/or elevated evening cortisol levels) is often observed among chronically stressed individuals and has been linked to poorer survival among breast cancer patients. We examined the association between race/ethnicity and other breast cancer risk factors with glucocorticogenic (G) activity, a measure that reflects plasma cortisol levels, in 503 controls from the San Francisco Bay Area Breast Cancer Study (SFBCS, 329 Hispanic, 100 NHB and 74 NHW women) using a low-cost Chemical-Activated LUciferase gene eXpression (CALUX) assay. Associations between G activity and sociodemographic and lifestyle factors were examined using multivariable linear regression models. Hispanic and NHB women had 14% (P = 0.016) and 16% (P = 0.007) lower morning G activity than NHW women, respectively. Additionally, we replicated our previously reported association between G activity and alcohol intake (women who drank >10 gm had 22% higher G activity than non-drinkers, P = 0.003). This association was only present in Hispanics and NHB. No statistically significant associations were observed between G activity and Indigenous American ancestry, body mass index, or neighborhood socioeconomic status. Our results indicate that NHB and Hispanic women may have a blunted cortisol awakening response potentially due to chronic stress. The increase in morning G activity observed with higher alcohol intake in Hispanics and NHB might reflect the use of alcohol as a stress-coping mechanism. Further research should assess the association between G activity and breast cancer survival in biospecimens from a prospective cohort so as to characterize the relationship between prediagnosis chronic stress and breast cancer outcome across different racial/ethnic groups. Citation Format: Rosemarie M. de la Rosa, Sylvia S. Sanchez, Phum Tachachartvanich, Heather Ruiz, Scarlett Lin Gomez, Esther M. John, Martyn T. Smith, Laura Fejerman. Plasma glucocorticogenic activity differs by race/ethnicity and alcohol intake among San Francisco Bay Area women [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A53.","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122341804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A24: Triple-negative breast Cancer risk: Ancestry and immune response","authors":"M. Ford, Erika T. Brown, David P Turner, V. Findlay, N. Esnaola, A. Alberg, S. Bolick, D. Hurley, R. Kramer, J. Salley, J. Cunningham","doi":"10.1158/1538-7755.DISP17-A24","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-A24","url":null,"abstract":"Background: Blacks in the U.S. have the worst breast cancer survival outcomes of any racial/ethnic group in the nation. However, blacks are not a monolithic group but are comprised of several ethnic groups. One such group in particular is the Sea Island or Gullah population of coastal South Carolina, North Carolina, Georgia, and Florida, whose ancestors came from coastal rice-growing areas of Africa. Sea Islanders (SI) have the lowest rates of European (non-Hispanic white) genetic admixture of any U.S. blacks, and are thus a special population who provide a rare opportunity to investigate genetic contributions to the profound ancestrally linked disparities in BC. Purpose: The purpose of this study was to identify, for the first time, frequencies of selected single nucleotide polymorphisms (SNPs) associated with triple-negative breast cancer (TNBC) in these three non-Hispanic population groups: whites, African Americans without Sea Island ancestry (AA), and African Americans with Sea Island ancestry (SI). Methods: Saliva samples were obtained using a mailed kit from a sample of 90 women in SC who had been diagnosed with TNBC in the past 1.5 years, recruited from the three population groups (30 women per group). Four SNPs on the 19p13 locus of BRCA 1 (rs8170, rs4808611, rs2363956, and rs3745185) were evaluated. Results: The percentage of TNBC cases was 6.7% among whites, 4.2% among SI blacks, and 22% among non-SI blacks. After controlling for TNBC status, similar allele frequencies for each SNP were seen in whites and SI blacks, compared to non-SI blacks (p Discussion: The prevalence of triple-negative breast cancer is significantly higher in African American women, and at younger ages, than in white women. Findings by Mukhtar et al. (2011) implicate immune function in the development of this aggressive breast cancer, as higher proliferating cellular nuclear antigen counts and tumor-associated macrophages were associated with hormone receptor-negative tumors and non-white ethnicity. Human populations differ in their transcriptional responses to immune challenges, and immune-responsive regulatory variants have participated in human adaptation by positive selection. Regulatory variants affecting steady-state gene expression and transcriptional responsiveness to immune challenges, particularly those that were viral related, may have been preferentially introduced into African genomes through admixture with Europeans, which may have conferred a natural selection disadvantage to modern blacks without SI ancestry. Such a natural selection disadvantage may mean that different immunologic therapeutic approaches are required for blacks with cancer than for whites with cancer, particularly for more aggressive disease. Citation Format: Marvella E. Ford, Erika T. Brown, David P. Turner, Victoria J. Findlay, Nestor F. Esnaola, Anthony J. Alberg, Susan Bolick, Deborah Hurley, Rita Kramer, Judith D. Salley, Joan E. Cunningham. Triple-negative breast Cancer risk: ","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"51 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128920329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A56: Racial disparities in colon cancer survival--United States, 2001-2009","authors":"A. White, D. Joseph, S. Rim, Christopher J. Johnson, M. Coleman, C. Allemani","doi":"10.1158/1538-7755.DISP17-A56","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-A56","url":null,"abstract":"Background: In the first CONCORD study, five-year survival for colon cancers diagnosed during 1990-1994 in the U.S. was among the highest in the world (60%), but there were large racial disparities in most participating states. The CONCORD-2 study updated these findings to determine survival trends up to 2009 by race and stage. Methods: We analyzed data from 37 state population-based cancer registries, covering approximately 80% of the U.S. population, for patients diagnosed with colon cancer during 2001-2009 and followed through 2009. Survival up to five years was adjusted for background mortality (net survival) using state- and race-specific life tables, and age-standardized using the International Cancer Survival Standard weights. Survival is presented by race (all, black, white), stage, state, and calendar period (2001–03 and 2004–09) to account for changes in methods used to collect stage. Results: Five-year net survival was 63.7% for those diagnosed during 2001-2003 and 64.6% for 2004-2009. More black than white patients were diagnosed at distant stage, both in 2001-2003 (21.5% vs. 17.2%, respectively) and in 2004-2009 (23.3% vs 18.8%). Survival varied widely between states and there was a slight increase in many states. Survival improved for both blacks and whites, but blacks had lower survival than whites diagnosed during 2001-2003 (54.7% vs. 64.5%) and 2004-2009 (56.6% vs. 65.4%). Conclusion: Five-year net survival from colon cancer remained stable over time. Survival remained lower in blacks than in whites but the gap narrowed. These finding suggest a need for more targeted efforts to improve screening and to ensure timely, appropriate treatment. Citation Format: Arica White, Djenaba Joseph, Sun Hee Rim, Christopher J. Johnson, Michel Coleman, Claudia Allemani. Racial disparities in colon cancer survival--United States, 2001-2009 [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A56.","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123317505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B77: Panel testing to evaluate genetic predisposition to breast cancer in African American women","authors":"Heather L. Blackburn, C. Shriver, R. Ellsworth","doi":"10.1158/1538-7755.DISP17-B77","DOIUrl":"https://doi.org/10.1158/1538-7755.DISP17-B77","url":null,"abstract":"Background: Although the role of BRCA1 and BRCA2 has been well studied in women of European ancestry, the contribution of these and other genes associated with hereditary cancers remains unknown in other populations. Here, we utilized panel testing to analyze 94 cancer predisposition genes in African American women (AAW) diagnosed with invasive breast cancer. Methods: 145 self-described AAW who enrolled in the Clinical Breast Care Project from 2001-2012 and had genomic DNA available were identified. Targeted sequencing was performed using the TruSight Cancer panel (Illumina). Pathogenic mutations were identified using VariantStudio and classified as pathogenic, uncertain significance (VUS), or benign using ClinVar. Results: Mean age at diagnosis was 52.1 years (range 25-81 years), and 32% of AAW had a family history. The majority of tumors were ER+HER2- (53%) followed by triple-negative breast cancer (TNBC, 34%). Seven percent of AAW had pathogenic mutations in high-risk genes including BRCA1 (n=7), BRCA2 (n=3), and TP53 (n=1); VUS were detected in BRCA1 (n=1) and BRCA2 (n=2); and an additional woman had a private variant (D2965E) in BRCA2. A further 1% of AAW harbored mutations in the moderate-penetrance gene CHEK2. VUS were also detected in ATM (n=9), CDH1 (n=1), CHEK2 (n=2), MSH2 (n=1), MSH6 (n=5), NBN (n=1), PALB2 (n=4), PMS2 (n=3), RAD51C (n=1), SMAD4 (n=1), TP53 (n=1), and TSC2 (n=1). Conclusions: Although 94 cancer predisposition genes were evaluated, pathogenic mutations in AAW were detected only in four well-established breast cancer predisposition genes (BRCA1, BRCA2, CHEK2, and TP53). Overall mutation frequency was 9%; however, an additional 25% of AAW harbored private variants and VUS, underscoring the critical need to establish the pathogenicity of these variants. The opinions or assertions contained herein are the private ones of the author/speaker and are not to be construed as official or reflecting the views of the Department of Defense, the Uniformed Services University of the Health Sciences, or any other agency of the U.S. Government. Citation Format: Heather L. Blackburn, Craig D. Shriver, Rachel E. Ellsworth. Panel testing to evaluate genetic predisposition to breast cancer in African American women [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B77.","PeriodicalId":147818,"journal":{"name":"Epidemiology, Lifestyle, and Genetics","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127159286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}