Prostate Cancer Disparities in Clinical Characteristics and Survival among Black and Latino Patients Considering Nativity: Findings from the California Cancer Registry.

BACKGROUND: We investigated clinical characteristics and prostate cancer survival patterns among Latino patients considering nativity compared with non-Latino Black (NLB) and non-Latino White (NLW) patients. METHODS: We used data from the California Cancer Registry (1995-2021), which included 347,540 NLW, 50,032 NLB, and 75,238 Latino patients with prostate cancer. Frequencies of sociodemographic and clinical variables were assessed using χ2 tests. Multivariable regression models were fitted to evaluate determinants of treatment reception, Gleason upgrade, and survival differences. Exploratory analyses were conducted grouping Latino cases into US born and non-US born by country of origin. RESULTS: Compared with NLW, NLB cases had the greatest proportion of younger patients, whereas non-US-born Latino patients had the greatest proportion of low socioeconomic status and uninsured patients. Non-US-born Latinos showed a greater proportion of diagnoses completed with <6 core biopsies, Gleason >8, stage IV tumors, and metastasis. Multivariable analyses showed that compared with NLW, Latino patients were as likely to receive treatment, whereas NLB cases were less likely (OR = 0.81; 95% confidence interval, 0.67-0.98; P = 0.029). Compared with NLW, non-US-born Latino cases were less likely to die of prostate cancer (HR = 0.78; 95% confidence interval, 0.64-0.94; P = 0.011), with no difference reported for NLB cases. CONCLUSIONS: Considering sociodemographic and clinical characteristics, non-US-born Latino patients with prostate cancer had better survival than NLW. This highlights the need to identify key determinants of these survival differences and the importance of sociodemographic and clinical determinants in survival disparities. IMPACT: Our study emphasizes the importance of considering nativity among Latino patients to understand prostate cancer disparities and outcomes in this population.

Population-based evaluation of disparities in stomach cancer by nativity among Asian and Hispanic populations in California, 2011-2015.

BACKGROUND: Stomach cancer incidence presents significant racial/ethnic disparities among racial/ethnic minority groups in the United States, particularly among Asian and Hispanic immigrant populations. However, population-based evaluation of disparities by nativity has been scarce because of the lack of nativity-specific population denominators, especially for disaggregated Asian subgroups. Population-based stomach cancer incidence and tumor characteristics by detailed race/ethnicity and nativity were examined. METHODS: Annual age-adjusted incidence rates were calculated by race/ethnicity, sex, and nativity and tumor characteristics, such as stage and anatomic subsite, were evaluated using the 2011-2015 California Cancer Registry data. For Hispanic and Asian populations, nativity-specific population counts were estimated using the US Census and the American Community Survey Public Use Microdata Sample data. RESULTS: During 2011-2015 in California, 14,198 patients were diagnosed with stomach cancer. Annual age-adjusted incidence rates were higher among foreign-born individuals than their US-born counterparts. The difference was modest among Hispanics (∼1.3-fold) but larger (∼2- to 3-fold) among Chinese, Japanese, and Korean Americans. The highest incidence was observed for foreign-born Korean and Japanese Americans (33 and 33 per 100,000 for men; 15 and 12 per 100,000 for women, respectively). The proportion of localized stage disease was highest among foreign-born Korean Americans (44%); a similar proportion was observed among US-born Korean Americans, although numbers were limited. For other Asians and Hispanics, the localized stage proportion was generally lower among foreign-born than US-born individuals and lowest among foreign-born Japanese Americans (23%). CONCLUSIONS: Nativity-specific investigation with disaggregated racial/ethnic groups identified substantial stomach cancer disparities among foreign-born immigrant populations.

Risk of Presenting with Poor-Prognosis Metastatic Cancer in Adolescents and Young Adults: A Population-Based Study.

Having metastatic disease at diagnosis poses the great risk of death among AYAs with cancer from all sociodemographic subgroups. This "landscape" study utilized United States Surveillance, Epidemiology, and End Results Program data from 2000−2016 to identify subgroups of AYAs at highest risk for presenting with metastases across twelve cancer sites having a poor-prognosis (5-year survival <50% with metastases). Adjusted odds ratios for risk of metastatic disease presentation were compared for AYAs in aggregate and by sociodemographic subgroup (race/ethnicity, sex, socioeconomic status [SES]). In general, AYAs who were male, racial/ethnic minorities, or low SES were at consistently greatest risk of metastases. Strikingly, having metastatic melanoma was independently associated with multiple AYA sociodemographic subgroups, including males (aOR 3.11 [95% CI 2.64−3.66]), non-Hispanic Blacks (4.04 [2.32−7.04]), Asian Pacific Islanders (2.99 [1.75−5.12]), Hispanics (2.37 [1.85−3.04]), and low SES (2.30 [1.89−2.80]). Non-Hispanic Blacks were more likely to present with metastatic cancer in all sites, except for bone, rhabdomyosarcoma, and stomach. Low SES AYAs are more likely to present with metastatic melanoma, bone tumors, soft tissue sarcomas, breast, cervical, lung, and stomach carcinomas. Building on these results, future cancer-specific studies should investigate the connection between sociodemographic risk factors and biological drivers of metastases. This line of research has potential to inform targeted public health and screening efforts to facilitate risk reduction and earlier detection of these deadly diseases.

Mitochondrial DNA haplogroup, genetic ancestry, and susceptibility to Ewing sarcoma.

Based on current studies, the incidence of Ewing sarcoma (ES) varies significantly by race and ethnicity, with the disease being most common in patients of European ancestry. However, race/ethnicity has generally been self-reported rather than formally evaluated at a population level using DNA evidence. Additionally, mitochondrial dysfunction is a hallmark of ES, yet there have been no reported studies of mitochondrial genetics in ES. Thus, we evaluated both the mitochondrial and nuclear ancestries of 420 pediatric ES patients in the United States using whole-genome sequencing. We found that the mitochondrial DNA (mtDNA) genomes of only six (1.4 %) patients belonged to African L haplogroups, while those of 90 % of the patients belonged to macrohaplogroup R, which includes haplogroup H, the most common maternal lineage in Europe. Compared to the general US population, European haplogroups were significantly enriched in ES patients (p < 2.2e-16) and the African haplogroups are significantly impoverished (p < 4.6e-16). Using the ancestry informative markers defined in a National Genographic study, the vast majority of patients exhibited significant nuclear ancestry originating from the Mediterranean, Northern Europe, and Southwest Asia, including all six patients with African L mtDNAs. Very few had primarily African nuclear ancestry. This is the first genomic epidemiology study to simultaneously interrogate the mitochondrial and nuclear ancestries of ES patients. While supporting previous findings of enriched European ancestry in ES patients, these results also suggest alternative hypotheses for the significant contribution of mitochondrial ancestry in ES patients, as well as the protective role of African ancestry.

Survival of Adolescents and Young Adults with Prevalent Poor-Prognosis Metastatic Cancers: A Population-Based Study of Contemporary Patterns and Their Implications.

BACKGROUND: Although survival has improved dramatically for most adolescents and young adults (AYA; 15-39 years old) with cancer, it remains poor for those presenting with metastatic disease. To better characterize this subset, we conducted a landscape survival comparison with older adults (40-79 years). METHODS: Using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, we examined incident cases of poor-prognosis metastatic cancers (5-year survival < 50%) among AYAs (n = 11,518) and older adults (n = 345,681) and compared cause-specific survival by sociodemographic characteristics (race/ethnicity, sex, and socioeconomic status). Adjusted HRs (aHR) for death from metastatic disease [95% confidence intervals (95% CI)] were compared between AYAs and older adults (Pint). RESULTS: AYAs had significantly better survival than older adults for every cancer site except kidney, where it was equivalent (range of aHRs = 0.91; 95% CI, 0.82-1.02 for kidney cancer to aHR = 0.33; 95% CI, 0.26-0.42 for rhabdomyosarcoma). Compared with their older adult counterparts, greater survival disparities existed for AYAs who were non-Hispanic Black with uterine cancer (aHR = 2.20; 95% CI, 1.25-3.86 versus aHR = 1.40; 95% CI, 1.28-1.54; Pint = 0.049) and kidney cancer (aHR = 1.51; 95% CI, 1.15-1.98 versus aHR = 1.10; 95% CI, 1.03-1.17; Pint = 0.04); non-Hispanic Asian/Pacific Islanders with ovarian cancer (aHR = 1.47; 95% CI, 1.12-1.93 versus aHR = 0.89; 95% CI, 0.84-0.95; Pint<0.001); and males with colorectal cancer (aHR = 1.21; 95% CI, 1.10-1.32 versus aHR = 1.08; 95% CI, 1.06-1.10; Pint = 0.045). CONCLUSIONS: AYAs diagnosed with these metastatic cancers have better survival than older adults, but outcomes remain dismal. IMPACT: Overcoming the impact of metastasis in these cancers is necessary for continuing progress in AYA oncology. Sociodemographic disparities affecting AYAs within kidney, uterine, ovarian, and colorectal cancer could indicate plausible effects of biology, environment, and/or access and should be explored.

Bariatric surgery in patients with breast and endometrial cancer in California: population-based prevalence and survival.

BACKGROUND: The number of bariatric surgeries performed in the United States has increased substantially since the 1990's. However, the prevalence and prognostic impact of bariatric surgery, or weight loss surgery (WLS), among patients with cancer are not known. OBJECTIVES: We investigated the population-based prevalence of WLS in women with breast or endometrial cancer and conducted exploratory analysis to examine whether postdiagnosis WLS is associated with survival. SETTING: Administrative statewide database. METHODS: WLS records for women with nonmetastasized breast (n = 395,146) or endometrial (n = 69,859) cancer were identified from the 1991-2014 California Cancer Registry data linked with the California Office of Statewide Health Planning and Development database. Characteristics of the patients were examined according to history of WLS. Using body mass index data available since 2011, a retrospective cohort of patients with breast or endometrial cancer and obesity (n = 12,540) was established and followed until 2017 (5% lost to follow-up). Multivariable cause-specific Cox proportional hazards models were used to examine the associations between postdiagnostic WLS and time to death. RESULTS: WLS records were identified for 2844 (.7%) patients with breast cancer and 1140 (1.6%) patients with endometrial cancer; about half of the surgeries were performed after cancer diagnosis. Postdiagnosis WLS was performed in ∼1% of patients with obesity and was associated with a decreased hazard for death (cause-specific hazard ratio = .37; 95% confidence interval = .014-.99; P = .049), adjusting for age, stage, co-morbidity, race/ethnicity, and socioeconomic status. CONCLUSION: About 2000 patients with breast or endometrial cancer in California underwent post-diagnosis WLS between 1991 and 2014. Our data support survival benefits of WLS after breast and endometrial cancer diagnosis.

Lymphoma-Associated Biomarkers Are Increased in Current Smokers in Twin Pairs Discordant for Smoking.

Smoking is associated with a moderate increased risk of Hodgkin and follicular lymphoma. To understand why, we examined lymphoma-related biomarker levels among 134 smoking and non-smoking twins (67 pairs) ascertained from the Finnish Twin Cohort. Previously collected frozen serum samples were tested for cotinine to validate self-reported smoking history. In total, 27 immune biomarkers were assayed using the Luminex Multiplex platform (R & D Systems). Current and non-current smokers were defined by a serum cotinine concentration of >3.08 ng/mL and ≤3.08 ng/mL, respectively. Associations between biomarkers and smoking were assessed using linear mixed models to estimate beta coefficients and standard errors, adjusting for age, sex and twin pair as a random effect. There were 55 never smokers, 43 current smokers and 36 former smokers. CCL17/TARC, sgp130, haptoglobin, B-cell activating factor (BAFF) and monocyte chemoattractant protein-1 (MCP1) were significantly (p < 0.05) associated with current smoking and correlated with increasing cotinine concentrations (Ptrend < 0.05). The strongest association was observed for CCL17/TARC (Ptrend = 0.0001). Immune biomarker levels were similar in former and never smokers. Current smoking is associated with increased levels of lymphoma-associated biomarkers, suggesting a possible mechanism for the link between smoking and risk of these two B-cell lymphomas.

Cancer Informatics for Cancer Centers: Scientific Drivers for Informatics, Data Science, and Care in Pediatric, Adolescent, and Young Adult Cancer.

Cancer Informatics for Cancer Centers (CI4CC) is a grassroots, nonprofit 501c3 organization intended to provide a focused national forum for engagement of senior cancer informatics leaders, primarily aimed at academic cancer centers anywhere in the world but with a special emphasis on the 70 National Cancer Institute-funded cancer centers. This consortium has regularly held topic-focused biannual face-to-face symposiums. These meetings are a place to review cancer informatics and data science priorities and initiatives, providing a forum for discussion of the strategic and pragmatic issues that we faced at our respective institutions and cancer centers. Here, we provide meeting highlights from the latest CI4CC Symposium, which was delayed from its original April 2020 schedule because of the COVID-19 pandemic and held virtually over three days (September 24, October 1, and October 8) in the fall of 2020. In addition to the content presented, we found that holding this event virtually once a week for 6 hours was a great way to keep the kind of deep engagement that a face-to-face meeting engenders. This is the second such publication of CI4CC Symposium highlights, the first covering the meeting that took place in Napa, California, from October 14-16, 2019. We conclude with some thoughts about using data science to learn from every child with cancer, focusing on emerging activities of the National Cancer Institute's Childhood Cancer Data Initiative.

Poor-Prognosis Metastatic Cancers in Adolescents and Young Adults: Incidence Patterns, Trends, and Disparities.

Background: For adolescents and young adults (AYAs, aged 15-39 years) with cancer, metastatic disease at diagnosis is the strongest predictor of mortality, but its associations with age and sociodemographic factors are largely unexplored. Methods: Using Surveillance, Epidemiology, and End Results Program data from 2000 to 2016, we collected incident cases of poor-prognosis metastatic cancer (5-year survival < 50%) and compared the proportion, incidence, time trends, and incidence rate ratios for race and ethnicity, sex, and socioeconomic status among AYAs, middle-aged adults (aged 40-64 years) and older adults (aged 65-79 years). Results: From 2000 to 2016, a total of 17 210 incident cases of poor-prognosis metastatic cancer were diagnosed in AYAs, 121 274 in middle-aged adults, and 364 228 in older adults. Compared with older patients, the proportion of AYAs having metastatic disease was equivalent or substantially lower in nearly every site except stomach and breast cancers, which were statistically significantly higher for AYAs compared with middle-aged and older adults (stomach: 57.3% vs 46.4% and 39.5%; breast: 6.6% vs 4.4% and 5.6%, respectively; 2-sided P < .001 for all comparisons). Incidence rates rose significantly faster among AYAs for breast, stomach, and kidney cancers and among AYAs and middle-aged adults for colorectal cancer. Markedly higher incidence rate ratios were noted for AYA racial and ethnic minorities with breast, stomach, and especially kidney cancer, where only non-Hispanic Black AYAs were at considerably higher risk. For most sites, incidence rate ratios were higher among male patients and individuals of low socioeconomic status across age groups. Conclusions: For most cancers, AYAs are not more likely to present with metastases than middle-aged and older adults. Further investigation is warranted for the disproportionate rise in incidence of metastatic breast, stomach, and kidney cancer among AYAs and their excess burden among AYA racial and ethnic minorities. The rising incidence of colorectal cancer among AYAs and middle-aged adults remains an additional concern.

Variability in Cytogenetic Testing for Multiple Myeloma: A Comprehensive Analysis From Across the United States.

PURPOSE: Multiple myeloma (MM) treatment has changed tremendously, with significant improvement in patient out-comes. One group with a suboptimal benefit is patients with high-risk cytogenetics, as tested by conventional karyotyping or fluorescence in situ hybridization (FISH). Methodology for these tests has been published, but not necessarily standardized. METHODS: We address variability in the testing and reporting methodology for MM cytogenetics in the United States using the ongoing African American Multiple Myeloma Study (AAMMS). We evaluated clinical and cytogenetic data from 1,221 patients (1,161 with conventional karyotyping and 976 with FISH) tested between 1998 and 2016 across 58 laboratories nationwide. RESULTS: Interlab and intralab variability was noted for the number of cells analyzed for karyotyping, with a significantly higher number of cells analyzed in patients in whom cytogenetics were normal (P 5.0025). For FISH testing, CD138-positive cell enrichment was used in 29.7% of patients and no enrichment in 50% of patients, whereas the remainder had unknown status. A significantly smaller number of cells was analyzed for patients in which CD138 cell enrichment was used compared with those without such enrichment (median, 50 v 200; P, .0001). A median of 7 loci probes (range, 1-16) were used for FISH testing across all laboratories, with variability in the loci probed even within a given laboratory. Chromosome 13-related abnormalities were the most frequently tested abnormality (n5956; 97.9%), and t(14;16) was the least frequently tested abnormality (n 5 119; 12.2%). CONCLUSIONS: We report significant variability in cytogenetic testing across the United States for MM, potentially leading to variability in risk stratification, with possible clinical implications and personalized treatment approaches.

A meta-analysis of genome-wide association studies of multiple myeloma among men and women of African ancestry.

Persons of African ancestry (AA) have a twofold higher risk for multiple myeloma (MM) compared with persons of European ancestry (EA). Genome-wide association studies (GWASs) support a genetic contribution to MM etiology in individuals of EA. Little is known about genetic risk factors for MM in individuals of AA. We performed a meta-analysis of 2 GWASs of MM in 1813 cases and 8871 controls and conducted an admixture mapping scan to identify risk alleles. We fine-mapped the 23 known susceptibility loci to find markers that could better capture MM risk in individuals of AA and constructed a polygenic risk score (PRS) to assess the aggregated effect of known MM risk alleles. In GWAS meta-analysis, we identified 2 suggestive novel loci located at 9p24.3 and 9p13.1 at P < 1 × 10-6; however, no genome-wide significant association was noted. In admixture mapping, we observed a genome-wide significant inverse association between local AA at 2p24.1-23.1 and MM risk in AA individuals. Of the 23 known EA risk variants, 20 showed directional consistency, and 9 replicated at P < .05 in AA individuals. In 8 regions, we identified markers that better capture MM risk in persons with AA. AA individuals with a PRS in the top 10% had a 1.82-fold (95% confidence interval, 1.56-2.11) increased MM risk compared with those with average risk (25%-75%). The strongest functional association was between the risk allele for variant rs56219066 at 5q15 and lower ELL2 expression (P = 5.1 × 10-12). Our study shows that common genetic variation contributes to MM risk in individuals with AA.

Emerging Cancer Survival Trends, Disparities, and Priorities in Adolescents and Young Adults: A California Cancer Registry-Based Study.

BACKGROUND: Although landmark studies in the 1990s demonstrated that adolescents and young adults (AYAs, ages 15-39 years) with cancer had lower survival improvement compared to other ages, therapeutic advances warrant reappraisal of those observations. We utilized more recent data to study site-specific AYA survival trends and disparities and gain a more contemporary understanding of this problem. METHODS: Using California Cancer Registry data from 1988 to 2014, we calculated 1) 5-year overall survival improvement for AYAs compared to other age groups; 2) hazard ratios (HRs) of death for AYAs comparing 2001-2014 with 1988-2000 stratified by site, stage, sex, age group, race and ethnicity, and socioeconomic status (SES); and 3) site-specific adjusted HRs (aHRs) for AYA risk groups and interaction analyses by time period. RESULTS: For all cancers combined, AYAs demonstrated survival improvement that exceeded all other age groups, largely due to reduced mortality in human immunodeficiency virus and acquired immunodeficiency syndrome-related cancers. The strongest predictor of death was cancer stage (aHR = 6.32 for distant vs localized, 95% confidence interval [CI] = 6.20 to 6.45). The aHR of death was statistically significantly higher for blacks (1.46, 95% CI = 1.42 to 1.50), Asian and Pacific Islanders (1.12, 95% CI = 1.09 to 1.15), and Latino whites (1.06, 95% CI = 1.04 to 1.08) compared to non-Latino whites, and was statistically significantly higher for low SES compared to high (1.31, 95% CI = 1.29 to 1.34). Survival disparities by stage, race and ethnicity, and SES worsened over time. CONCLUSIONS: For AYAs in aggregate, the historical cancer survival improvement gap has been closed. However, the growing survival disparities in AYA subsets reported here, including advanced stage disease, racial and ethnic minorities, and low SES, highlight new priorities in need of increased attention, including inequities in cancer care and delivery within this vulnerable population.

DNA methylation patterns of adult survivors of adolescent/young adult Hodgkin lymphoma compared to their unaffected monozygotic twin.

DNA methylation (DNAm) silences gene expression and may play a role in immune dysregulation that is characteristic of adolescent/young adult Hodgkin lymphoma (AYAHL). We used the Infinium HumanMethylation27 BeadChip to quantify DNAm in blood (N = 9 pairs, mean age 57.4 y) or saliva (N = 36 pairs, mean age 50.0 y) from long-term AYAHL survivors and their unaffected co-twins. Epigenetic aging (DNAm age) was calculated using previously described methods and compared between survivors and co-twins using paired t-tests and analyses were stratified by sample type, histology, sex, age at sample collection and time since diagnosis. Differences in blood DNAm age were observed between survivors and unaffected co-twins (64.1 vs. 61.3 years, respectively, p = .04), especially in females (p = .01); no differences in saliva DNAm age were observed. Survivors and co-twins had 74 (in blood DNA) and 6 (in saliva DNA) differentially methylated loci. Our results suggest persistent epigenetic aging in AYAHL survivors long after HL cure.

A Reappraisal of Sex-Specific Cancer Survival Trends Among Adolescents and Young Adults in the United States.

BACKGROUND: Cancer survival among adolescents and young adults (AYAs) was previously reported as showing little or no improvement compared to younger or older counterparts. The role of the HIV/AIDS epidemic in the AYA survival deficit has not been evaluated. METHODS: Using cancer registry data from the Surveillance, Epidemiology, and End Results program (SEER 9), we examined sex-specific 5-year relative survival trends for children (0-14 years old), AYAs (15-39 years old), and older adults (40 years and older) diagnosed with cancer during 1973-2009 and followed through the end of 2014. The analysis was conducted with and without Kaposi sarcoma (KS) and lymphomas, and by two time periods: 1973-1977 (before the human immunodeficiency virus/acquired immunodeficiency syndrome [HIV/AIDS] epidemic) and 2005-2009 (after the HIV/AIDS epidemic waned). RESULTS: A total of 3 209 721 invasive cancer cases were included in the study (27 646 children, 213 930 AYAs, and 2 968 145 older adults; 24 803 children, 178 741 AYAs, and 2 844 062 older adults when KS and lymphoma cases were excluded). We found that 5-year relative survival for AYAs exceeded that of children and older adults before the onset of the HIV/AIDS epidemic (eg, during 1973-1979, 0.58-0.67 among male AYAs as compared with 0.47-0.61 for male children and 0.36-0.42 for male older adults; among female AYAs, the numbers were 0.73-0.77 as compared with 0.51-0.65 for female children and 0.52-0.55 for female older adults); substantially declined during 1983-1997 when HIV/AIDS lacked effective treatment among male AYAs; and returned to be higher than most age groups by the late 1990s after HIV/AIDS was controlled. Nonetheless, comparison of survival improvement between 1973-1977 and 2005-2009 demonstrated less progress in AYAs than other age groups, which was due to AYAs' better baseline survival and larger survival gains among children and older adults in recent years. CONCLUSIONS: Apart from the temporary impact of HIV/AIDS, survival among AYA cancer patients has shown sustained improvement and superiority relative to other age groups. However, these encouraging findings do not negate the distinctive challenges in cancer diagnosis, treatment, and survivorship faced by AYAs.

Birth Anomalies in Monozygotic and Dizygotic Twins: Results From the California Twin Registry.

BACKGROUND: Inherited factors and maternal behaviors are thought to play an important role in the etiology of several congenital malformations. Twin studies can offer additional evidence regarding the contribution of genetic and lifestyle factors to common birth anomalies, but few large-scale studies have been reported. METHODS: We included data from twins (20,803 pairs) from the population-based California Twin Program. We compared concordance in monozygotic (MZ) to dizygotic (DZ) twins for the following birth anomalies: clubfoot, oral cleft, spina bifida, muscular dystrophy, deafness, cerebral palsy, strabismus, and congenital heart defects. Each birth anomaly was also examined for the associations with birth characteristics (birthweight and birth order) and parental exposures (age, smoking, and parental education). RESULTS: The overall prevalence of any selected birth anomaly in California twins was 38 per 1,000 persons, with a slightly decreasing trend from 1957-1982. For pairwise concordance in 6,752 MZ and 7,326 like-sex DZ twin pairs, high MZ:DZ concordance ratios were observed for clubfoot (CR 5.91; P = 0.043) and strabismus (CR 2.52; P = 0.001). Among the total 20,803 pairs, parental smoking was significantly associated with risk of spina bifida (OR 3.48; 95% CI, 1.48-8.18) and strabismus (OR 1.61; 95% CI, 1.28-2.03). A significant quadratic trend of increasing risk for clubfoot, spina bifida, and strabismus was found when examining whether father smoked, mother smoked, or both parents smoked relative to non-smoking parents (P = 0.029, 0.026, and 0.0005, respectively). CONCLUSIONS: Our results provide evidence for a multifactorial etiology underlying selected birth anomalies. Further research is needed to understand the biological mechanisms.

HLA expression and HLA type associations in relation to EBV status in Hispanic Hodgkin lymphoma patients.

A proportion of classical Hodgkin lymphomas harbor the Epstein Barr virus (EBV). We previously demonstrated that associations between Human Leukocyte Antigen (HLA) alleles and susceptibility to EBV+ classical Hodgkin lymphoma differ between European and Chinese populations. Data on Hispanic populations is missing. Here we examined the association between HLA type, tumor cell HLA expression and other characteristics in Hispanic Hodgkin lymphoma patients. Hispanic Hodgkin lymphoma patients diagnosed at the Los Angeles County-University of Southern California Medical Center from 2000-2012 were included (n = 65). Formalin-fixed paraffin-embedded tumor tissue was analyzed for EBV by in situ hybridization and for HLA class I and class II expression by immunohistochemistry. HLA typing was performed by HLA-A specific quantitative PCR of genomic DNA from tissue. Thirty patients (46%) had EBV+ tumors. Expression of HLA class I (p = 0.0006) was significantly associated with EBV+ tumor status in Hispanic patients, similar to Europeans and Chinese. A positive association between HLA class II expression and EBV+ tumor status, as present in large studies in Europeans, was not found (p = 0.06). The prevalences of the specific European HLA-A*01 risk and European HLA-A*02 protective types were not significantly associated with EBV+ tumors among these Hispanic patients, however numbers were too low to draw firm conclusions. The HLA-A*02:07 allele, that is associated with EBV+ Hodgkin lymphoma in Chinese, was absent. In conclusion, the association between EBV positivity in tumor cells and HLA class I expression appears to be consistent across different populations. Larger studies in Hispanics are needed to evaluate HLA allele susceptibility associations.

Stomach Cancer Disparity among Korean Americans by Tumor Characteristics: Comparison with Non-Hispanic Whites, Japanese Americans, South Koreans, and Japanese.

Background: Stomach cancer incidence shows substantial racial-ethnic disparity in the United States, with Korean Americans experiencing by far the highest incidence. We examined stomach cancer incidence trends in Korean Americans by tumor subsite, histology, and stage and compared them with incidence rates in racial-ethnic groups with the second highest rate (Japanese Americans) and the lowest rate (non-Hispanic whites; NHWs) as well as populations in South Korea and Japan.Methods: We calculated age-adjusted incidence rates by racial-ethnic groups, sex, and tumor characteristics, using the 1988-2012 California Cancer Registry data. Data on South Korea and Japan were obtained from the literature and other resources.Results: Between 1988 and 2012 in California, Korean Americans had about five times greater incidence than NHWs and twice that of Japanese Americans. Tumor characteristics differed by ethnic group and gender. The incidence in Korean Americans has declined during recent years, for both cardia and noncardia sites and for both intestinal- and diffuse-type histology. Although Korean Americans were diagnosed at an earlier stage than other Californians, the proportion with localized disease (43%) was much smaller than in South Korea (57%), where population-based screening is available.Conclusions: Stomach cancer incidence declined in the highest risk ethnic groups. However, the persistent disparity between Korean Americans and other racial-ethnic groups warrants additional strategies for prevention and earlier diagnosis.Impact: Analysis of California Cancer Registry data identified a racial-ethnic subgroup with stomach cancer disparity that may benefit from targeted prevention and screening efforts. Cancer Epidemiol Biomarkers Prev; 26(4); 587-96. ©2016 AACR.

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

BACKGROUND: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. METHODS: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. RESULTS: We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10-7) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. IMPACT: A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR.