Host genetic variants, Epstein-Barr virus subtypes, and the risk of nasopharyngeal carcinoma: Assessment of interaction and mediation.

Epstein-Barr virus (EBV) and human leukocyte antigen (HLA) polymorphisms are well-known risk factors for nasopharyngeal carcinoma (NPC). However, the combined effects between HLA and EBV on the risk of NPC are unknown. We applied a causal inference framework to disentangle interaction and mediation effects between two host HLA SNPs, rs2860580 and rs2894207, and EBV variant 163364 with a population-based case-control study in NPC-endemic southern China. We discovered the strong interaction effects between the high-risk EBV subtype and both HLA SNPs on NPC risk (rs2860580, relative excess risk due to interaction [RERI] = 4.08, 95% confidence interval [CI] = 2.03-6.14; rs2894207, RERI = 3.37, 95% CI = 1.59-5.15), accounting for the majority of genetic risk effects. These results indicate that HLA genes and the high-risk EBV have joint effects on NPC risk. Prevention strategies targeting the high-risk EBV subtype would largely reduce NPC risk associated with EBV and host genetic susceptibility.

Considerations towards the better integration of epidemiology into quantitative risk assessment.

Environmental epidemiology has proven critical to study various associations between environmental exposures and adverse human health effects. However, there is a perception that it often does not sufficiently inform quantitative risk assessment. To help address this concern, in 2017, the Health and Environmental Sciences Institute initiated a project engaging the epidemiology, exposure science, and risk assessment communities with tripartite representation from government agencies, industry, and academia, in a dialogue on the use of environmental epidemiology for quantitative risk assessment and public health decision making. As part of this project, four meetings attended by experts in epidemiology, exposure science, toxicology, statistics, and risk assessment, as well as one additional meeting engaging funding agencies, were organized to explore incentives and barriers to realizing the full potential of epidemiological data in quantitative risk assessment. A set of questions was shared with workshop participants prior to the meetings, and two case studies were used to support the discussion. Five key ideas emerged from these meetings as areas of desired improvement to ensure that human data can more consistently become an integral part of quantitative risk assessment: 1) reducing confirmation and publication bias, 2) increasing communication with funding agencies to raise awareness of research needs, 3) developing alternative funding channels targeted to support quantitative risk assessment, 4) making data available for reuse and analysis, and 5) developing cross-disciplinary and cross-sectoral interactions, collaborations, and training. We explored and integrated these themes into a roadmap illustrating the need for a multi-stakeholder effort to ensure that epidemiological data can fully contribute to the quantitative evaluation of human health risks, and to build confidence in a reliable decision-making process that leverages the totality of scientific evidence.

Environmental epidemiology and risk assessment: Exploring a path to increased confidence in public health decision-making.

Throughout history, environmental epidemiology has proven crucial to identify certain threats to human health and to provide a basis for the development of life-saving public health policies. However, epidemiologists are facing challenges when studying tenuous threats such as environmental exposure to chemicals, whose association with adverse health effects may be difficult to characterize. As a result, epidemiological data can seldom be fully leveraged for quantitative risk assessment and decision-making. Despite two decades of efforts to improve a more systematic integration of human data to evaluate human health risks, assessors still heavily rely on animal data to do so, while epidemiology plays more of a secondary role. Although the need for more and better collaboration between risk assessors and epidemiologists is widely recognized, both fields tend to remain siloed. In 2017, the Health and Environmental Sciences Institute initiated a project engaging the epidemiology, exposure science, and regulatory communities with tripartite representation from regulators, industry, and academia in a dialogue on the use of environmental epidemiology for regulatory decision-making. Several focus groups attended by epidemiology, exposure science, and risk assessment experts were organized to explore incentives and barriers to collaboration, to ultimately bridge the gap between the various disciplines, and to realize the full potential of epidemiological data in risk assessment. Various ideas that have emerged from these meetings could help ensure the better integration of epidemiological data in quantitative risk assessment and contribute to building confidence in a robust and science-based regulatory decision-making process.

Reproductive history and risk of nasopharyngeal carcinoma: A population-based case-control study in southern China.

OBJECTS: Nasopharyngeal carcinoma (NPC) incidence exhibits a remarkable sex disparity, with higher risk among males. Whether this pattern can be partly explained by female reproductive history is unclear. METHODS: A population-based case-control study of NPC was conducted in southern China between 2010 and 2014, including 674 histopathologically verified female NPC cases and 690 female controls randomly selected from population-based registries. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression after adjusting for potential confounders. RESULTS: Women who had 3, 4, or ≥5 pregnancies compared with 2 pregnancies were at significantly increased risk for NPC (ORs 1.56, 1.45 and 1.88, respectively). History of deliveries was similarly associated with a greater risk of NPC. These positive associations were more prominent in women who were younger than 50 years, had less than 10 years of education, or were white-collar workers. Increasing time since menopause was associated with a diminished NPC risk (Ptrend = 0.010). Women more than 15 years after menopause had a 0.35-fold (95% CI: 0.16-0.75) NPC risk compared with those 0-3 years after menopause. CONCLUSION: Contrary to our hypothesis, a history of pregnancy or delivery increased the risk of NPC and the risk decreased with increasing time since menopause. However, the non-linear relationship and no consistent risk patterns across strata indicate that the observed associations are unlikely to be causal, and may at least partially be ascribed to residual confounding by socioeconomic factors.

Are We Winning or Losing the Battle With Periprosthetic Joint Infection: Trends in Periprosthetic Joint Infection and Mortality Risk for the Medicare Population.

BACKGROUND: Periprosthetic joint infection (PJI) is a potentially deadly complication of total joint arthroplasty. This study was designed to address how the incidence of PJI and outcome of treatment, including mortality, are changing in the population over time. METHODS: Primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients with PJI from the 100% Medicare inpatient data set (2005-2015) were identified. Cox proportional hazards regression models for risk of PJI after THA/TKA (accounting for competing risks) or risk of all-cause mortality after PJI were adjusted for patient and clinical factors, with year included as a covariate to test for time trends. RESULTS: The unadjusted 1-year and 5-year risk of PJI was 0.69% and 1.09% for THA and 0.74% and 1.38% for TKA, respectively. After adjustment, PJI risk did not change significantly by year for THA (P = .63) or TKA (P = .96). The unadjusted 1-year and 5-year overall survival after PJI diagnosis was 88.7% and 67.2% for THA and 91.7% and 71.7% for TKA, respectively. After adjustment, the risk of mortality after PJI decreased significantly by year for THA (hazard ratio = 0.97; P < .001) and TKA (hazard ratio = 0.97; P < .001). CONCLUSION: Despite recent clinical focus on preventing PJI, we are unable to detect substantial decline in the risk of PJI over time, although mortality after PJI has declined. Because PJI risk appears not to be changing over time, the incidence of PJI is anticipated to scale up proportionately with the demand for THA and TKA, which is projected to increase substantially in the coming decade.

An Assessment of the Cox Proportional Hazards Regression Model for Epidemiologic Studies.

The basic assumptions of the Cox proportional hazards regression model are rarely questioned. This study addresses whether hazard ratio, i.e., relative risk (RR), estimates using the Cox model are biased when these assumptions are violated. We investigated also the dependence of RR estimates on temporal exposure characteristics, and how inadequate control for a strong, time-dependent confounder affects RRs for a modest, correlated risk factor. In a realistic cohort of 500,000 adults constructed using the National Cancer Institute Smoking History Generator, we used the Cox model with increasing control of smoking to examine the impact on RRs for smoking and a correlated covariate X. The smoking-associated RR was strongly modified by age. Pack-years of smoking did not sufficiently control for its effects; simultaneous control for effect modification by age and time-dependent cumulative exposure, exposure duration, and time since cessation improved model fit. Even then, residual confounding was evident in RR estimates for covariate X, for which spurious RRs ranged from 0.980 to 1.017 per unit increase. Use of the Cox model to control for a time-dependent strong risk factor yields unreliable RR estimates unless detailed, time-varying information is incorporated in analyses. Notwithstanding, residual confounding may bias estimated RRs for a modest risk factor.

Low-level arsenic exposure and developmental neurotoxicity in children: A systematic review and risk assessment.

UNLABELLED: Risk assessments of arsenic have focused on skin, bladder, and lung cancers and skin lesions as the sensitive cancer and non-cancer health endpoints, respectively; however, an increasing number of epidemiologic studies that can inform risk assessment have examined neurodevelopmental effects in children. We conducted a systematic review and risk assessment based on the epidemiologic literature on possible neurodevelopmental effects at lower arsenic exposures. Twenty-four cross-sectional, case-control, and cohort studies were identified that report on the association between low-level arsenic exposure (i.e., largely <100 µg/L of arsenic in drinking water) and neurological outcomes in children. Although the overall evidence does not consistently show a causal dose-response relationship at low doses, the most rigorously conducted studies from Bangladesh indicate possible inverse associations with cognitive function, predominantly involving concurrent arsenic exposure as measured by biomarkers (i.e., arsenic in urine or blood) and raw verbal test scores at ages 5-11 years. Issues such as non-comparability of outcome measures across studies; inaccuracies of biomarkers and other measures of inorganic arsenic exposure; potential effect modification by cultural practices; insufficient adjustment for nutritional deficiencies, maternal IQ, and other important confounders; and presence of other neurotoxicants in foreign populations limit generalizability to U.S. POPULATIONS: Of the few U.S. studies available, the most rigorously conducted study did not find a consistent dose-response relationship between arsenic concentrations in tap water or toenails and decrements in IQ scores. Assuming that the strongest dose-response relationship from the most rigorous evidence from Bangladesh is generalizable to U.S. populations, possible reference doses were estimated in the range of 0.0004-0.001 mg/kg-day. These doses are higher than the U.S. Environmental Protection Agency reference dose for chronic lifetime exposure, thus indicating protectiveness of the existing value for potential neurotoxicity in children. This reference dose is undergoing revision as EPA considers various health endpoints in the reassessment of inorganic arsenic health risks.

Body mass index and risk of death in Asian Americans.

OBJECTIVES: We investigated the association between body mass index (BMI) and mortality among Asian Americans. METHODS: We pooled data from prospective cohort studies with 20 672 Asian American adults with no baseline cancer or heart disease history. We estimated hazard ratios and 95% confidence intervals (CIs) with Cox proportional hazards models. RESULTS: A high, but not low, BMI was associated with increased risk of total mortality among individuals aged 35 to 69 years. The BMI was not related to total mortality among individuals aged 70 years and older. With a BMI 22.5 to < 25 as the reference category among never-smokers aged 35 to 69 years, the hazard ratios for total mortality were 0.83 (95% CI = 0.47, 1.47) for BMI 15 to < 18.5; 0.91 (95% CI = 0.62, 1.32) for BMI 18.5 to < 20; 1.08 (95% CI = 0.86, 1.36) for BMI 20 to < 22.5; 1.14 (95% CI = 0.90, 1.44) for BMI 25 to < 27.5; 1.13 (95% CI = 0.79, 1.62) for BMI 27.5 to < 30; 1.82 (95% CI = 1.25, 2.64) for BMI 30 to < 35; and 2.09 (95% CI = 1.06, 4.11) for BMI 35 to 50. Higher BMI was also related to increased cardiovascular disease and cancer mortality. CONCLUSIONS: High BMI is associated with increased mortality risk among Asian Americans.

Enigmatic sex disparities in cancer incidence.

In this study we aimed to identify cancers where there is a consistent sex disparity, with the goal of identifying unexplained sex disparities that may offer promising opportunities for etiologic research. Age- and sex-specific cancer incidence data from Cancer Incidence in Five Continents, provided by the International Agency for Research on Cancer, were used to calculate incidence rate ratios for 35 cancer sites, comparing men to women, adjusting for attained age, gross domestic product (GDP), and geographical region. Genital cancers and breast cancer were excluded. The consistency of relative risks was examined by GDP and geographical region and, in a subset of longstanding cancer registers, by calendar year. For each cancer site, the sex disparity was broadly classified as plausibly explained by established environmental risk factors, partly explained, or unexplained. Cancer incidence was statistically significantly higher in men than women at 32 of 35 sites, with disparities >2-fold for 15 sites and >4-fold for 5 sites. For nearly all sites, the sex disparity was consistent across GDP groups and geographical regions. However, the incidence rate ratios varied considerably by age at diagnosis. The sex disparity for 13 cancer sites was considered to be entirely unexplained by known risk factors; these sites showed strikingly little variation in the incidence rate ratios over decades. Thus, the basis of many of the largest sex disparities in cancer incidence seems mostly unknown, highlighting the need for intensified research into its origins.

Nativity and papillary thyroid cancer incidence rates among Hispanic women in California.

BACKGROUND: Overall, the incidence of papillary thyroid cancer in Hispanic women residing in the United States (US) is similar to that of non-Hispanic white women. However, little is known as to whether rates in Hispanic women vary by nativity, which may influence exposure to important risk factors. METHODS: Nativity-specific incidence rates among Hispanic women were calculated for papillary thyroid cancer using data from the California Cancer Registry (CCR) for the period 1988-2004. For the 35% of cases for whom birthplace information was not available from the CCR, nativity was statistically imputed based on age at Social Security number issuance. Population estimates were extracted based on US Census data. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were also estimated. RESULTS: In young (age <55 years) Hispanic women, the incidence of papillary thyroid cancer among US-born women (10.65 per 100,000) was significantly greater than that for foreign-born women (6.67 per 100,000; IRR, 1.60 [95% CI, 1.44-1.77]). The opposite pattern was observed in older women. The age-specific patterns showed marked differences by nativity: among foreign-born women, rates increased slowly until age 70 years, whereas among US-born women, incidence rates peaked during the reproductive years. Incidence rates increased over the study period in all subgroups. CONCLUSION: Incidence rates of papillary thyroid cancer vary by nativity and age among Hispanic women residing in California. These patterns can provide insight for future etiologic investigations of modifiable risk factors for this increasingly common and understudied cancer.

Head and neck cancer-specific survival based on socioeconomic status in Asians and Pacific Islanders.

BACKGROUND: Lower socioeconomic status (SES) has been linked to higher incidence of head and neck cancer (HNC) and lower survival. However, little is known about the effect of SES on HNC survival in Asians and Pacific Islanders (APIs). This study's purpose was to examine the effect of SES on disease-specific survival (DSS) and overall survival (OS) in APIs with HNC using population-based data. METHODS: A total of 53,544 HNC patients (4,711 = APIs) were identified from the California Cancer Registry from 1988 to 2007. Neighborhood (block-group-level) SES, based on composite Census 1990 and 2000 data, was calculated for each patient based on address at diagnosis, categorized into statewide quintiles, and collapsed into 2 groups for comparison (low SES = quintiles 1-3; high SES = quintiles 4-5). DSS and OS were computed by the Kaplan-Meier method. Adjusted hazards ratios (HR) were estimated using Cox proportional hazards regression models. RESULTS: Among APIs, lower neighborhood SES was significantly associated with poorer DSS (HR range for oral cavity, oropharynx, or larynx/hypopharynx cancer, 1.07-1.34) and OS (HR, 1.13-1.37) after adjusting for patient and tumor characteristics. Lower SES was significantly associated with poorer survival in API with all HNC sites combined: DSS HR: 1.26 (95% confidence interval [CI], 1.08-1.48) and OS HR, 1.30 (95% CI, 1.16-1.45). CONCLUSIONS: Neighborhood SES was associated with longer DSS and OS in API with HNC. The effect of SES on HNC survival should be considered in future studies, and particular attention should be paid to clinical care of lower-SES HNC patients.

Papillary thyroid cancer incidence rates vary significantly by birthplace in Asian American women.

OBJECTIVE: To investigate how birthplace influences the incidence of papillary thyroid cancer among Asian American women. METHODS: Birthplace- and ethnic-specific age-adjusted and age-specific incidence rates were calculated using data from the California Cancer Registry for the period 1988-2004. Birthplace was statistically imputed for 30% of cases using a validated imputation method based on age at Social Security number issuance. Population estimates were obtained from the US Census. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated for foreign-born vs. US-born women. RESULTS: Age-adjusted incidence rates of papillary thyroid cancer among Filipina (13.7 per 100,000) and Vietnamese (12.7) women were more than double those of Japanese women (6.2). US-born Chinese (IRR = 0.48, 95% CI: 0.40-0.59) and Filipina women (IRR = 0.74, 95% CI: 0.58-0.96) had significantly higher rates than those who were foreign-born; the opposite was observed for Japanese women (IRR = 1.55, 95% CI: 1.17-2.08). The age-specific patterns among all foreign-born Asian women and US-born Japanese women showed a slow steady increase in incidence until age 70. However, among US-born Asian women (except Japanese), substantially elevated incidence rates during the reproductive and menopausal years were evident. CONCLUSIONS: Ethnic- and birthplace-variation in papillary thyroid cancer incidence can provide insight into the etiology of this increasingly common and understudied cancer.

Disparities in liver cancer incidence by nativity, acculturation, and socioeconomic status in California Hispanics and Asians.

BACKGROUND: Asians and Hispanics have the highest incidence rates of liver cancer in the United States, but little is known about how incidence patterns in these largely immigrant populations vary by nativity, acculturation, and socioeconomic status (SES). Such variations can identify high-priority subgroups for prevention and monitoring. METHODS: Incidence rates and rate ratios (IRR) by nativity among 5,400 Hispanics and 5,809 Asians diagnosed with liver cancer in 1988-2004 were calculated in the California Cancer Registry. Neighborhood ethnic enclave status and SES were classified using 2000 U.S. Census data for cases diagnosed in 1998-2002. RESULTS: Foreign-born Hispanic males had significantly lower liver cancer incidence rates than U.S.-born Hispanic males in 1988-2004 (e.g., IRR = 0.54, 95% confidence interval [CI] = 0.50-0.59 in 1997-2004), whereas foreign-born Hispanic females had significantly higher rates in 1988-1996 (IRR = 1.42, 95% CI = 1.18-1.71), but not 1997-2004. Foreign-born Asian males and females had up to 5-fold higher rates than the U.S.-born. Among Hispanic females, incidence rates were elevated by 21% in higher-enclave versus lower-enclave neighborhoods, and by 24% in lower- versus higher-SES neighborhoods. Among Asian males, incidence rates were elevated by 23% in higher-enclave neighborhoods and by 21% in lower-SES neighborhoods. In both racial/ethnic populations, males and females in higher-enclave, lower-SES neighborhoods had higher incidence rates. CONCLUSIONS: Nativity, residential enclave status, and neighborhood SES characterize Hispanics and Asians with significantly unequal incidence rates of liver cancer, implicating behavioral or environmental risk factors and revealing opportunities for prevention. IMPACT: Liver cancer control efforts should especially target foreign-born Asians, U.S.-born Hispanic men, and residents of lower-SES ethnic enclaves.

Disparities in breast cancer survival among Asian women by ethnicity and immigrant status: a population-based study.

OBJECTIVES: We investigated heterogeneity in ethnic composition and immigrant status among US Asians as an explanation for disparities in breast cancer survival. METHODS: We enhanced data from the California Cancer Registry and the Surveillance, Epidemiology, and End Results program through linkage and imputation to examine the effect of immigrant status, neighborhood socioeconomic status, and ethnic enclave on mortality among Chinese, Japanese, Filipino, Korean, South Asian, and Vietnamese women diagnosed with breast cancer from 1988 to 2005 and followed through 2007. RESULTS: US-born women had similar mortality rates in all Asian ethnic groups except the Vietnamese, who had lower mortality risk (hazard ratio [HR] = 0.3; 95% confidence interval [CI] = 0.1, 0.9). Except for Japanese women, all foreign-born women had higher mortality than did US-born Japanese, the reference group. HRs ranged from 1.4 (95% CI = 1.2, 1.7) among Koreans to 1.8 (95% CI = 1.5, 2.2) among South Asians and Vietnamese. Little of this variation was explained by differences in disease characteristics. CONCLUSIONS: Survival after breast cancer is poorer among foreign- than US-born Asians. Research on underlying factors is needed, along with increased awareness and targeted cancer control.

Hidden breast cancer disparities in Asian women: disaggregating incidence rates by ethnicity and migrant status.

OBJECTIVES: We estimated trends in breast cancer incidence rates for specific Asian populations in California to determine if disparities exist by immigrant status and age. METHODS: To calculate rates by ethnicity and immigrant status, we obtained data for 1998 through 2004 cancer diagnoses from the California Cancer Registry and imputed immigrant status from Social Security Numbers for the 26% of cases with missing birthplace information. Population estimates were obtained from the 1990 and 2000 US Censuses. RESULTS: Breast cancer rates were higher among US- than among foreign-born Chinese (incidence rate ratio [IRR] = 1.84; 95% confidence interval [CI] = 1.72, 1.96) and Filipina women (IRR = 1.32; 95% CI = 1.20, 1.44), but similar between US- and foreign-born Japanese women. US-born Chinese and Filipina women who were younger than 55 years had higher rates than did White women of the same age. Rates increased over time in most groups, as high as 4% per year among foreign-born Korean and US-born Filipina women. From 2000-2004, the rate among US-born Filipina women exceeded that of White women. CONCLUSIONS: These findings challenge the notion that breast cancer rates are uniformly low across Asians and therefore suggest a need for increased awareness, targeted cancer control, and research to better understand underlying factors.

Racial and social class gradients in life expectancy in contemporary California.

Life expectancy, or the estimated average age of death, is among the most basic measures of a population's health. However, monitoring differences in life expectancy among sociodemographically defined populations has been challenging, at least in the United States (US), because death certification does not include collection of markers of socioeconomic status (SES). In order to understand how SES and race/ethnicity independently and jointly affected overall health in a contemporary US population, we assigned a small-area-based measure of SES to all 689,036 deaths occurring in California during a three-year period (1999-2001) overlapping the most recent US census. Residence at death was geocoded to the smallest census area available (block group) and assigned to a quintile of a multifactorial SES index. We constructed life tables using mortality rates calculated by age, sex, race/ethnicity and neighborhood SES quintile, and produced corresponding life expectancy estimates. We found a 19.6 (+/-0.6) year gap in life expectancy between the sociodemographic groups with the longest life expectancy (highest SES quintile of Asian females; 84.9 years) and the shortest (lowest SES quintile of African-American males; 65.3 years). A positive SES gradient in life expectancy was observed among whites and African-Americans but not Hispanics or Asians. Age-specific mortality disparities varied among groups. Race/ethnicity and neighborhood SES had substantial and independent influences on life expectancy, underscoring the importance of monitoring health outcomes simultaneously by these factors. African-American males living in the poorest 20% of California neighborhoods had life expectancy comparable to that reported for males living in developing countries. Neighborhood SES represents a readily-available metric for ongoing surveillance of health disparities in the US.

Uncovering disparities in survival after non-small-cell lung cancer among Asian/Pacific Islander ethnic populations in California.

Asians may have better survival after non-small-cell lung cancer (NSCLC) than non-Asians. However, it is unknown whether survival varies among the heterogeneous U.S. Asian/Pacific Islander (API) populations. Therefore, this study aimed to quantify survival differences among APIs with NSCLC. Differences in overall and disease-specific survival were analyzed in the California Cancer Registry among 16,577 API patients diagnosed with incident NSCLC between 1988 and 2007. Adjusted hazard ratios (HR) with 95% confidence intervals (95% CI) were estimated using Cox proportional hazards regression models with separate baseline hazards by disease stage. Despite better overall and disease-specific survival among APIs compared with non-Hispanic Whites, differences were evident across API populations. Among women, Japanese (overall survival HR, 1.16; 95% CI, 1.06-1.27) and APIs other than those in the six largest ethnic groups (other APIs; HR, 1.19; 95% CI, 1.07-1.33) had significantly poorer overall and disease-specific survival than Chinese. By contrast, South Asian women had significantly better survival than Chinese (HR, 0.79; 95% CI, 0.63-0.97). Among men, Japanese (HR, 1.15; 95% CI, 1.07-1.24), Vietnamese (HR, 1.07; 95% CI, 1.00-1.16), and other APIs (HR, 1.18; 95% CI, 1.08-1.28) had significantly poorer overall and disease-specific survival than Chinese. Other factors independently associated with poorer survival were lower neighborhood socioeconomic status, involvement with a non-university hospital, unmarried status, older age, and earlier year of diagnosis. APIs have significant ethnic differences in NSCLC survival that may be related to disparate lifestyles, biology, and especially health care access or use. To reduce the nationwide burden of lung cancer mortality, it is critical to identify and ameliorate hidden survival disparities such as those among APIs.

Disparities in survival after Hodgkin lymphoma: a population-based study.

Survival after Hodgkin lymphoma (HL) is generally favorable, but may vary by patient demographic characteristics. The authors examined HL survival according to race/ethnicity and neighborhood socioeconomic status (SES), determined from residential census-block group at diagnosis. For 12,492 classical HL patients ≥ 15 years diagnosed in California during 1988-2006 and followed through 2007, we determined risk of overall and HL-specific death using Cox proportional hazards regression; analyses were stratified by age and Ann Arbor stage. Irrespective of disease stage, patients with lower neighborhood SES had worse overall and HL-specific survival than patients with higher SES. Patients with the lowest quintile of neighborhood SES had a 64% (patients aged 15-44 years) and 36% (≥ 45 years) increased risk of HL-death compared to patients with the highest quintile of SES; SES results were similar for overall survival. Even after adjustment for neighborhood SES, blacks and Hispanics had increased risks of HL-death 74% and 43% (15-44 years) and 40% and 17% (≥ 45 years), respectively, higher than white patients. The racial/ethnic differences in survival were evident for all stages of disease. These data provide evidence for substantial, and probably remediable, racial/ethnic and neighborhood SES disparities in HL outcomes.

3 For Life: a model pilot program to prevent hepatitis B virus infection and liver cancer in Asian and Pacific Islander Americans.

PURPOSE: 3 For Life aims to increase hepatitis B virus (HBV) awareness and reduce the high prevalence of undiagnosed chronic HBV infection and susceptibility among Asian/Pacific Islander (API) adults. DESIGN: This pilot program offered low-cost HBV vaccination with free HBV testing targeted primarily at foreign-born Chinese adults. SETTING: Semimonthly screening and vaccination clinics were held in San Francisco, California, for 1 year. SUBJECTS: A total of 1206 adults accessed the program. INTERVENTION: Participants paid a discounted fee for a full vaccine series against HBV, hepatitis A virus (HAV), or both. Participants also provided blood samples for HBV serologic testing. Test results, recommendations, and appointment reminders were provided by mail. MEASURES: We compared the probability of completing a recommended vaccine series by HBV serologic status and sociodemographic characteristics. ANALYSIS: Proportions were compared using multivariate logistic regression models. RESULTS: Nine percent of adults were chronically infected with HBV, and 53% were unprotected. In the latter group, 85% completed the HBV vaccine series. The probability of completing a recommended hepatitis vaccine series was similar across most sociodemographic groups, with slightly higher completion rates among middle-aged and Chinese participants. CONCLUSIONS: Lessons learned from this pilot program have been used toward successful replication in other cities, demonstrating that 3 For Life is an accessible, affordable, reproducible, and sustainable model to increase HBV awareness, testing, and prevention among API adults.

Infectious mononucleosis, childhood social environment, and risk of Hodgkin lymphoma.

Infectious mononucleosis (IM) has been associated with an increased risk of Hodgkin lymphoma (HL), implicating a role for Epstein-Barr virus (EBV) in HL development. Although essential to the understanding of the association, it has remained uncertain if the relationship is restricted to the EBV-positive subset of HL. We collected information on mononucleosis history and childhood socioenvironmental characteristics in a population-based study of 586 patients with classic HL and 3,187 controls in Denmark and Sweden. Tumor EBV status was established for 499 cases by immunohistochemistry and in situ hybridization techniques. Odds ratios (OR) for the relationship between HL risk and mononucleosis and other risk factors were estimated by logistic regression for HL in younger (18-44 years) and older (45-74 years) adults, overall and by tumor EBV status. All analyses were adjusted for country-specific measures of maternal education and mononucleosis history. IM was associated with an increased risk of EBV-positive [OR, 3.23; 95% confidence interval (95% CI) 1.89-5.55] but not EBV-negative HL (OR, 1.35; 95% CI, 0.86-2.14). Risk of EBV-positive HL varied with time since IM and was particularly pronounced in younger adults (OR, 3.96; 95% CI, 2.19-7.18). IM-associated lymphomas occurred with a median of 2.9 years (1.8-4.9 years) after infection. The EBV specificity of the IM association was corroborated by a case-case comparison of IM history between younger adult EBV-positive and EBV-negative HL patients (OR(IM EBV+ HL versus EBV- HL), 2.68; 95% CI, 1.40-5.12). We found further evidence that IM is associated only with EBV-positive HL. This finding is compatible with the notion that EBV-positive and EBV-negative HL may have different etiologies.