Hodgkin lymphoma incidence in California Hispanics: influence of nativity and tumor Epstein-Barr virus.

PURPOSE: For classical Hodgkin lymphoma (HL), migrant studies could elucidate contributions of environmental factors (including Epstein-Barr virus (EBV)) to the lower rates in non-whites. Given the well-described etiologic complexity of HL, this research requires a large, immigrant population, such as California Hispanics. METHODS: With 1988-2004 California Cancer Registry data (2,595 Hispanic, 8,637 white HL cases) and tumor cell EBV status on a subset (218 Hispanics, 656 whites), we calculated ethnicity- and nativity-specific HL incidence rates simultaneously by age, sex, and histologic subtype, and tumor cell EBV prevalence. RESULTS: Compared with white rates, Hispanic HL rates were lower overall (70 %) and for nodular sclerosis HL, particularly among young adults (60-65 % for females). However, they were higher among children (200 %) and older adults, and for mixed cellularity HL. Compared with rates in foreign-born Hispanics, rates in US-born Hispanics were higher among young adults (>threefold in females), lower for children and adults over age 70, and consistently intermediate compared with rates in whites. EBV tumor prevalence was 67, 32, and 23 % among foreign-born Hispanics, US-born Hispanics, and whites, respectively, although with variation by age, sex, and histology. CONCLUSIONS: Findings strongly implicate environmental influences, such as nativity-related sociodemographic differences, on HL occurrence. In addition, lower young adult rates and higher EBV prevalence in US-born Hispanics than in whites raise questions about the duration/extent of environmental change for affecting HL rates and also point to ethnic differences in genetic susceptibility. Lesser variation in mixed cellularity HL rates and greater variation in rates for females across groups suggest less modifiable factors interacting with environmental influences.

Cigarette smoking and risk of Hodgkin lymphoma and its subtypes: a pooled analysis from the International Lymphoma Epidemiology Consortium (InterLymph).

BACKGROUND: The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes. PATIENTS AND METHODS: Through the InterLymph Consortium, 12 case-control studies regarding cigarette smoking and HL were identified. Pooled analyses on the association between smoking and HL stratified by tumor histology and Epstein-Barr virus (EBV) status were conducted using random effects models adjusted for confounders. Analyses included 3335 HL cases and 14 278 controls. RESULTS: Overall, 54.5% of cases and 57.4% of controls were ever cigarette smokers. Compared with never smokers, ever smokers had an odds ratio (OR) of HL of 1.10 [95% confidence interval (CI) 1.01-1.21]. This increased risk reflected associations with mixed cellularity cHL (OR = 1.60, 95% CI 1.29-1.99) and EBV-positive cHL (OR = 1.81, 95% CI 1.27-2.56) among current smokers, whereas risk of nodular sclerosis (OR = 1.09, 95% CI 0.90-1.32) and EBV-negative HL (OR = 1.02, 95% CI 0.72-1.44) was not increased. CONCLUSION: These results support the notion of etiologic heterogeneity between HL subtypes, highlighting the need for HL stratification in future studies. Even if not relevant to all subtypes, our study emphasizes that cigarette smoking should be added to the few modifiable HL risk factors identified.

A review of AI and Data Science support for cancer management.

INTRODUCTION: Thanks to improvement of care, cancer has become a chronic condition. But due to the toxicity of treatment, the importance of supporting the quality of life (QoL) of cancer patients increases. Monitoring and managing QoL relies on data collected by the patient in his/her home environment, its integration, and its analysis, which supports personalization of cancer management recommendations. We review the state-of-the-art of computerized systems that employ AI and Data Science methods to monitor the health status and provide support to cancer patients managed at home. OBJECTIVE: Our main objective is to analyze the literature to identify open research challenges that a novel decision support system for cancer patients and clinicians will need to address, point to potential solutions, and provide a list of established best-practices to adopt. METHODS: We designed a review study, in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, analyzing studies retrieved from PubMed related to monitoring cancer patients in their home environments via sensors and self-reporting: what data is collected, what are the techniques used to collect data, semantically integrate it, infer the patient's state from it and deliver coaching/behavior change interventions. RESULTS: Starting from an initial corpus of 819 unique articles, a total of 180 papers were considered in the full-text analysis and 109 were finally included in the review. Our findings are organized and presented in four main sub-topics consisting of data collection, data integration, predictive modeling and patient coaching. CONCLUSION: Development of modern decision support systems for cancer needs to utilize best practices like the use of validated electronic questionnaires for quality-of-life assessment, adoption of appropriate information modeling standards supplemented by terminologies/ontologies, adherence to FAIR data principles, external validation, stratification of patients in subgroups for better predictive modeling, and adoption of formal behavior change theories. Open research challenges include supporting emotional and social dimensions of well-being, including PROs in predictive modeling, and providing better customization of behavioral interventions for the specific population of cancer patients.

Epstein-barr virus-associated malignancies: epidemiologic patterns and etiologic implications.

Epstein-Barr virus (EBV), a ubiquitous B-lymphotrophic herpesvirus, has been found in the tumor cells of a heterogeneous group of malignancies (Burkitt's lymphoma, lymphomas associated with immunosuppression, other non-Hodgkin's lymphomas, Hodgkin's disease, nasopharyngeal carcinoma, gastric adenocarcinoma, lymphoepithelioma-like carcinomas, and immunodeficiency-related leiomyosarcoma). As the epidemiologic characteristics of these cancers have not been considered together, this review seeks to relate their incidence patterns and risk factors to EBV biology and virus-host interaction in an attempt to help elucidate factors involved in EBV-related carcinogenesis. We include a brief review of EBV virology and primary infection to provide a biologic context for considering the epidemiology, summarize the most salient epidemiologic features of each malignancy, synthesize epidemiologic data by risk factor to uncover commonalities and informative contrasts across the diseases, and propose hypotheses regarding etiologic mechanisms, based on the possible effect of the risk factors at various stages in the viral life cycle.

Predictors of misclassification of Hispanic ethnicity in a population-based cancer registry.

PURPOSE: Hispanic ethnicity is often used as a category for calculating population-based rates or assessing risk of epidemiologic studies. However, ethnic misclassification can lead to false conclusions unless the extent of misclassification and the characteristics of those misclassified are understood. METHODS: This study explored determinants of ethnic misclassification in a sample of 1154 cancer cases in the San Francisco-Oakland cancer registry, where ethnic classification is based on surname or medical record report. We compared the following: correctly classified Hispanics, persons classified as Hispanic who self-identified as non-Hispanic, and persons classified as non-Hispanic who self-identified as Hispanic. RESULTS: Among men classified as Hispanic, those most likely to self-identify as non-Hispanic did not speak Spanish, had non-Spanish surnames, and were recent immigrants. Women misclassified as Hispanic did not speak Spanish or have Spanish maiden names, nor did they have mothers with Spanish maiden names. Persons who called themselves Hispanic, but were misclassified by the registry, were likely to be non-Spanish speaking college-education males. CONCLUSIONS: Researchers using ethnicity should be aware of how ethnicity was determined and how this classification may bias or confound their results.

Black-white differences in Hodgkin's disease incidence in the United States by age, sex, histology subtype and time.

Black-white differences in Hodgkin's disease (HD) occurrence have been reported in older US mortality statistics and in limited international data, suggesting either genetic or socioeconomic determinants of susceptibility. However, there has been no evaluation with reliable data of the interracial incidence patterns by age, sex, and histologic subtype, that are prerequisite to understanding the causes of such variation. This project utilized 15 years of recent, high quality, incidence data from well-defined black and white US populations to calculate age-, sex-, and histology-specific rates of HD by race over time. Rates were somewhat lower for blacks (N = 593) than whites (N = 8,541) of both sexes, except among young boys. For blacks, age-specific incidence curves were slightly bimodal, although less than for whites; the male excess of HD was larger; and rates among women were low at all ages. For each histology subtype, blacks had lower incidence than whites; however, for the first time, nodular sclerosis was found to be the most common variant for both races. Between 1969-74 and 1980-84, HD rates declined in whites over age 55 but increased in white young adult women; among blacks, rates decreased slightly for boys and young adult men, the latter likely due to improving population enumeration. These findings confirm some interracial differences noted previously in HD. For blacks, they also reveal an incipiently bimodal age incidence and more prominent nodular sclerosis subtype occurrence that support a strong role for environmental factors in racial variation of this lymphoma.

Age variation in Hodgkin's disease risk factors in older women: evidence from a population-based case-control study.

Hodgkin's disease (HD), which affects all age groups, has been associated with childhood social class, particularly among adults under age 40. Little is known about social class risk factors in older adults, and the few existing studies have conflicting findings. As part of a population-based case-control study of HD in women, we examined social class risk factors by diagnostic age groups (45-54 years and 55-79 years) corresponding to incidence patterns and by histologic subtypes based on a uniform pathologic review. Among women ages 45-54, cases were more likely to be Catholic, to have lower income and to be taller than controls. Among women ages 55-79, cases tended to have come from small or large childhood households, lived in single-family childhood housing, and had a single rather than shared bedroom at age 11. For the nodular sclerosis (NS) histologic subtype, similar age differences in risk factors were apparent. Comparisons between the NS and non-NS subtypes in women ages 55-79 identified some common risk factors (single-family childhood home, single bedroom at age 11) but others specific to one subtype (childhood household size, adult height for NS; lower maternal education for non-NS). Thus, some social class associations with HD differed between middle-aged and older women, as well as between these groups and younger adults, while others were shared across age groups. Risk also was associated with both higher and lower childhood social class in middle-aged and older women, in contrast with previous findings. None of these patterns was explained entirely by histologic subtype but may reflect age and histology subtype variation in the HD-EBV association.

Accuracy of racial classification of Vietnamese patients in a population-based cancer registry.

Racial classification of Asian subgroups is increasingly important for health statistics, given the growing Asian-American populations. This study reports the reliability of racial classification of Vietnamese in population-based cancer registry data from northern California. From the Greater Bay Area Cancer Registry, we selected 2240 persons diagnosed with cancer in 1989-1992 and whom the registry considered Vietnamese by birthplace and/or registry race and/or surname, or who were Southeast Asian or Chinese by race. One thousand ninety persons (49%) were interviewed. Sensitivity and predictive value positive, and cancer incidence rates, were calculated using different combinations of the classification factors (birthplace, registry race, and name). By registry-reported race alone, 74% of those the registry classified as Vietnamese agreed with this classification on interview, while 90% of those identifying themselves as Vietnamese were so classified. With classification based on 2 of 3 factors, 78% of those classified as Vietnamese agreed, and 91% of self-reported Vietnamese were correctly classified. Misclassification was associated with age, sex, year of immigration, education, and language use. Registry-based annual age-adjusted all-site cancer incidence rates per 100,000 for Vietnamese were 287.7 for males and 221.3 for females. Rates adjusted for self-reported ethnicity were 242.8 (male) and 213.7 (female). Registry classification of Vietnamese is currently problematic. Approximately 20% of cancer cases classified as Vietnamese are probably not Vietnamese. The higher incidence rates for Vietnamese in the United States than in Vietnam partly may reflect such classification error.

A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus.

Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI) = 0.76-0.86, P(combined) = 3.5 × 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.

Reproductive factors in Hodgkin's disease in women: a review.

Understanding of Hodgkin's disease causes continues to be elusive. The prime etiologic candidate, Epstein-Barr virus, has been detected in only a proportion of cases, and there are few other active leads. Epidemiologic data reviewed here describe sex differences in Hodgkin's disease consistent with an involvement of reproductive and thus hormonal factors in its pathogenesis in women. This hypothesis has received very little research attention. Yet, the male predominance in incidence shows variation with age, particularly around the childbearing years, that is unusual for a malignancy. Indirect evidence relating Hodgkin's disease incidence to marital status, religion, and population parity trends demonstrates lower rates in women of presumed higher parity. Two studies that examined parity found strong but opposing associations with risk of Hodgkin's disease. The role of parity is difficult to interpret because of study design differences and the likelihood of confounding by social class. However, the incidence, clinical, and experimental findings, which should not be due to social class differences between men and women, are also compatible with a protective influence of reproductive experience in Hodgkin's disease in women. Prior infection with any ubiquitous virus seems unlikely to explain the sex differences in descriptive statistics. On the whole, the evidence suggests a role of hormonal factors in the pathogenesis of Hodgkin's disease, possibly operating through an effect on the immune system, and this hypothesis may prove fruitful to explore.

Regional variation in Hodgkin's disease incidence by histologic subtype in the US.

Geographic distribution in Hodgkin's disease (HD) incidence was examined for whites by age, sex and Rye histologic subtype in several regions of the US for 1969 to 1971 and 1973 to 1980, using data from national cancer surveys. Average annual age-adjusted rates (1973-1980) ranged between 2.0 and 3.6 per 100,000 persons. Significant regional variation in HD was confined to elevated rates in Connecticut and San Francisco-Oakland, and low rates in Hawaii, Atlanta, and New Orleans. In young adults (ages 20-34 years) HD was positively associated across regions with rates for children (ages 5-14 years), and with community-wide socioeconomic status (SES), but did not vary with older adult rates. Patterns of geographic variation differed among the histologic subtypes, with no significant variation for the lymphocyte predominance form. Incidence of nodular sclerosis increased with regional SES, and was inversely correlated with rates of lymphocyte predominance. Among women, HD incidence became less heterogeneous across regions with time.

Recent incidence and secular trends in Hodgkin's disease and its histologic subtypes.

Incidence data from national cancer surveys (1947, 1969-71, 1973-80) in selected regions of the United States were used to describe the epidemiology of Hodgkin's disease (HD) in whites over all regions by age, sex and Rye histologic subtype in the 1970s, and time trends for HD overall. Before 1971, rates increased in young adults, notably men, and in older persons. During the 1970s, rates in children were stable, but young adult rates were high and rose slightly, particularly among women; both trends reflected elevated incidence of Nodular Sclerosis, the only subtype with increasing rates. For adults over 40, rates of all subtypes declined after 1969-71. Thus HD incidence in this country is not static, even over the last decade. Rate stability in younger children may indicate disappearance of environmentally caused HD. Incidence declines for older persons suggest a cohort effect, depletion of young adult susceptibles, or improvements in diagnostic accuracy.

Spatial clustering of Hodgkin's disease in the San Francisco Bay area.

Numerous investigations of time-space clustering in Hodgkin's disease, designed to investigate its communicability, have produced equivocal results. Few studies have considered the spatial clustering reflecting a broader range of exposures despite sporadic evidence of such groupings of Hodgkin's disease cases. This project examined spatial (residential) patterns among 741 white Hodgkin's disease cases from the San Francisco-Oakland, California, area using 1969-1977 cancer registry incidence data and 1970 population counts. Two types of distances between cases were evaluated using new statistical methods that adjust for population density. Hodgkin's disease cases lived closer to their nearest case neighbors than expected in four of five study counties. Significant clustering of this type occurred among case subgroups defined by sex, age, and social class. There was little evidence of larger-scale clustering around a single point-source exposure. The small, widely dispersed clusters detected here suggest late exposure to a ubiquitous environmental agent involved in Hodgkin's disease etiology. These case aggregations are consistent both with prior reports of spatial clustering in this lymphoma and with evidence implicating viral or other factors in its pathogenesis.

The epidemiology of Hodgkin's disease.

Much of the epidemiological heterogeneity of HD incidence reflects the behaviour of the NS subtype, at least in the USA. Incidence variation across races (except Asians) and time periods is most marked in this subtype. In young adults with HD, there is compelling evidence for social class modification of risk consistent with an infectious aetiology; limited data suggest that this effect occurs within the NS subtype, but considerable evidence indicates that it does not primarily involve EBV infection. Findings from familial aggregation studies and HLA associations point to inherited susceptibility to this subtype. Despite little sex difference for NS in young adulthood in the latest incidence data, parity nevertheless appears to be protective against this subtype for women. Therefore, the greater increase for females than males in the incidence of young-adult NS in recent years may reflect the impact of population trends towards later childbearing and lower parity. This change, as well as the concomitant smaller family sizes and growing affluence, could explain part of the burgeoning incidence of NS in young adults in the USA. These observations suggest that NS in young adults constitutes a separate disease, probably of infectious origin. The incongruous occurrence of this subtype in older adults, and the presence of EBV in some NS cases, could reflect heterogeneity within NS, for example, representing features of the cellular phase of NS (Cozen et al, 1992; Medeiros and Greiner, 1995). For the non-NS subtypes, many of the factors that predict risk of NS may also be relevant. Patterns of social class determinants in children and older adults, the age groups at risk for MC, support involvement of an infectious precursor given intense exposure, and EBV is a likely candidate, based on its high prevalence in these groups. However, little aetiological research has been directed explicitly at the non-NS subtypes. Considerable effort has gone into exploring an infectious aetiology of HD. Recently, this line of investigation has moved beyond social class determinants to molecular epidemiological studies of EBV and, to a lesser degree, other potentially involved viruses. The roles of genetic susceptibility and sex hormones also represent promising areas for exploration, particularly in their possible interaction with infectious agents and other environmental factors. Ultimately, clearer epidemiological understanding of HD will be aided by more precise classification of this disease at the molecular level.

Time trends in Hodgkin's disease incidence. The role of diagnostic accuracy.

A prior study of Hodgkin's disease (HD) incidence using national cancer survey data (1969-1980) identified unprecedented rate declines among white persons older than 40 years, and rate increases among young adults aged 15 through 39. These trends could be due to improved diagnostic accuracy. To investigate this hypothesis, the authors updated incidence rates in whites by age, sex, and histologic subtype through 1984; quantified diagnostic accuracy in corresponding detail using Repository Center for Lymphoma Clinical Studies data, which include original and expert review diagnoses on lymphoma patients; and recalculated HD incidence rates (1969-1984) corrected for diagnostic error. Updated HD incidence rates through 1984 continued to decline in older adults and showed persistent increases for young adults with the nodular sclerosis (NS) histologic subtype. The percentage of original HD diagnoses confirmed on review (confirmation rate) decreased with age and increased over time; in older adults, these patterns opposed observed incidence trends. However, for young adults, confirmation rates of NS, the most common subtype at these ages, were high and changed little over time. After adjustment for diagnostic error, incidence rates for older adults were lower than previously observed and showed no secular changes. However, young adults with NS had slightly larger rate increases than in uncorrected data. Thus, contemporary changes in HD incidence for whites primarily involve growing risk to persons at the start of adult life. These patterns are compatible with trends in suspected sociodemographic risk factors that suggest an infectious etiology for HD.

Epidemiologic trends in HIV-associated lymphomas.

Infection with HIV increases the risk of developing non-Hodgkin lymphoma and, to a lesser extent, Hodgkin disease. The introduction of highly active antiretroviral therapy (HAART) in 1996 changed the natural history of HIV disease, but the HIV-infected population also has changed in composition. Accordingly, the epidemiology of HIV-associated lymphomas now differs from that observed in the first 15 years of the HIV epidemic. In populations with access to HAART, reductions in lymphoma risk have been reported for NHL and suggested for Hodgkin disease, but long-term risks are as yet unknown. Lymphomas are increasingly common cancers in persons with HIV and are fatal in most patients, warranting continued attention to their incidence and etiology.

Age-specific survival after Hodgkin's disease in a population-based cohort (United States).

OBJECTIVE: To examine risk factors for disease-specific survival in young and older adults diagnosed with Hodgkin's disease (HD) in a representative case series of adequate size for detecting effect modification by age group. METHODS: For 5630 young adults (ages 15-44) and 2424 older adults (ages 45 and older) diagnosed with HD and reported to the population-based Surveillance, Epidemiology, and End Results program of the National Cancer Institute between 1983 and 1995, Kaplan-Meier survival curves were constructed and Cox proportional hazards regression used to evaluate the influences of age, sex, race/ethnicity, histologic subtype, Ann Arbor stage at diagnosis, and calendar year on hazard of disease-specific death. RESULTS: The effects of most previously studied risk factors for HD death were different for young and older adults. Age was not associated with disease-specific survival in young adults, but in older adults, 1-year increases in age elevated the relative hazard of HD death by 4 6%. Male sex was related to outcome in young but not older adults, and Ann Arbor stage and B-symptom status exhibited markedly different relationships to survival by age. Older adult patients with and without B-symptoms had different hazards of mortality and had to be assessed separately. CONCLUSIONS: Factors associated with disease-specific survival were different for young and older adults with HD. These findings provide further support for two etiologically and clinically distinct disease entities.