Roberts, Lewis R

Clinical studies have identified specific genetic variants in dihydropyrimidine dehydrogenase (DPD; DPYD gene) as predictors of severe adverse toxicity to the commonly used chemotherapeutic 5‐fluorouracil (5‐FU); however, these studies have focused on European and European‐American populations. Our laboratory recently demonstrated that additional variants in non‐European haplotypes are predictive of 5‐FU toxicity. The objective of this study was to identify potential risk variants in an understudied East African population relevant to our institution's catchment area. The DPYD protein‐coding region was sequenced in 588 individuals of Somali or Kenyan ancestry living in central/southeast Minnesota. Twelve novel nonsynonymous variants were identified, seven of which significantly decreased DPD activity in vitro. The commonly reported toxicity‐associated variants, *2A, D949V, and I560S, were not detected in any individuals. Overall, this study demonstrates a critical limitation in our knowledge of pharmacogenetic predictors of 5‐FU toxicity, which has been based on clinical studies conducted in populations of limited diversity.

Background: We used metabolic risk factors to estimate the prevalence and clinical significance of nonalcoholic fatty liver disease in Asian Americans with hepatocellular carcinoma (HCC). Methods: This is a retrospective cohort study of 824 consecutive Asian HCC patients at Stanford University Medical Center from 1998 to 2015. Patients were subdivided as: Chinese, other East Asian (Japanese and Korean), South East Asian (Vietnamese, Thai, and Laotian), Maritime South East Asian (MSEA: Malaysian, Indonesian, Filipino, and Singaporean), and South West Asian (Indian, Pakistani, and Middle Eastern). Metabolic risk factors studied were body mass index, hypertension, type II diabetes, and hyperlipidemia. Results: Most patients were male (76%) with mean age 63 years. Metabolic risk factors were highly prevalent on presentation and increased over time (P<0.001), as did the prevalence of cryptogenic HCC (P<0.004). Compared with other Asian subgroups, MSEAs had the highest body mass index (26.3) and higher rates of type II diabetes (44% vs. 23% to 35%, P=0.004), hypertension (59% vs. 38% to 55%, P=0.04), and cryptogenic HCC (15% vs. 4% to 10%, P=0.01). They were more likely to be symptomatic on presentation (44% vs. 32% to 58%, P=0.07), less likely to present within Milan criteria (34% vs. 35% to 63%, P<0.0001), and trended toward decreased 10-year survival rates compared with other ethnic subgroups (9% vs. 25% to 32%, P=0.07). Conclusions: Metabolic risk factors were increasingly prevalent among Asian Americans with HCC. MSEAs, who had the highest incidence of these risk factors, had more advanced tumor stage and trended toward worse survival.

BACKGROUNDThere is global variation in the onset of hepatocellular carcinoma (HCC). The objective of the current study was to investigate the impact of country of birth on age at the time of HCC diagnosis in the United States.METHODSIncident HCC cases diagnosed between 2000 and 2012 in the Surveillance, Epidemiology, and End Results program 18 registry were included. Factors associated with very early onset (age at diagnosis < 40 years) and early onset (age at diagnosis < 50 years) were identified by logistic regression.RESULTSA total of 59,907 patients were included. The median age at the time of diagnosis of HCC was 62 years and 76% of the patients were male. Of the 75% of patients for whom information regarding birth country was available, 29% were foreign born. In multivariate logistic regression, birth in West Africa (adjusted odds ratio [AOR], 16.3; 95% confidence interval [95% CI], 9.2‐27.9 [P<.01]), Central/South/other Africa (AOR, 11.0; 95% CI, 4.5‐23.7 [P<.01]), Oceania (AOR, 4.9; 95% CI, 2.9‐8.0 [P<.01]), and East Africa (AOR, 3.5; 95% CI, 1.5‐6.8 [P<.01]) was found to have the strongest association with very early‐onset HCC after adjusting for sex and race/ethnicity. Birth in West Africa, Central/South/other Africa, Oceania, or East Africa also was found to be strongly associated with early‐onset HCC.CONCLUSIONSBirth country was found to be independently associated with age at the time of HCC diagnosis in the United States. Birth in Africa (except for North Africa) and Oceania was strongly associated with very early‐onset HCC. These findings have implications for the design of comprehensive HCC surveillance programs in the United States. Cancer 2016. © 2016 American Cancer Society. Cancer 2017;81–89. © 2016 American Cancer Society.

Abstract Background: African immigrants in the US have substantially higher prevalences of viral hepatitis and hepatocellular carcinoma than the general population. In Minnesota, which has the third largest state population of African immigrants in the US, the incidence and mortality for hepatocellular carcinoma among Blacks is 3 times higher than Caucasians (The 2012 Minnesota Department of Health Cancer Report). Most African immigrants are unaware of their risk for hepatocellular carcinoma which contributes to substantial liver health disparities. Limited research exists on the burden of viral hepatitis and hepatocellular carcinoma among African immigrants. Thus, we conducted a pilot study to evaluate the knowledge, attitudes, and behaviors (KAB) of African immigrants related to liver disease. Methods: The study used a community-engaged research framework. The research team consisted of stakeholders from an academic medical center and Ethiopian, Liberian, and Kenyan community-based organizations and faith-based centers. A semi-structured focus group guide was developed using a KAB approach with open-ended questions. Content analysis was used to thematically code the transcribed data. Qualitative analysis software (ATLAS.TI) was used to organize codes and highlight major themes contributing to liver health disparities. Results: We enrolled 63 participants and conducted 9 focus groups (1 in Amharic, 2 in Oromo, and 6 in English) in Rochester and Minneapolis, Minnesota. The mean age was 47±19; 32 participants (51%) were male; the median years lived in the US was 12 years. General knowledge of the modes of transmission of viral hepatitis and of the prevention and development of liver cancer was minimal. Themes related to barriers to viral hepatitis screening and vaccination included perceived cultural stigma and use of traditional remedies. Common sources of general health information included internet, pamphlets, friends, family, spiritual leaders and healthcare professionals. Healthcare professionals are the source for information on screening, prevention, transmission and treatment of viral hepatitis and liver cancer. Most participants sought healthcare at reputable medical institutions. Media sources and community-based events at faith-centers were preferred modes of information dissemination on viral hepatitis and liver cancer screening and prevention. Conclusions: Participants identified several factors contributing to the increased burden of hepatocellular carcinoma in Minnesota including lack of knowledge of disease transmission and progression, cultural stigma/taboos, and lack of preventive care. Culturally and linguistically appropriate interventions are needed to increase awareness, prevention, early detection, and treatment of viral hepatitis and liver cancer among African immigrants in Minnesota. Citation Format: Essa A. Mohamed, Nasra H. Giama, Hassan M. Shaleh, Linda M. Kerandi, Abdul M. Oseini, Hager F. Ahmed Mohammed, Henry M. Kerandi, Dekermue Togbah, Abdiwahab O. Ali, Ibrahim A. Waaeys, Hamdi A. Ali, Safra A. Mohamed, Hawa M. Ali, Joyce E. Balls-Berry, Lewis R. Roberts. Evaluating knowledge, attitudes, and behaviors about viral hepatitis and hepatocellular carcinoma among recent African immigrants in Minnesota: A community-engaged qualitative study. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C01.