Ellen T. Chang

The Enigmatic Epidemiology of Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) has a unique and complex etiology that is not completely understood. Although NPC is rare in most populations, it is a leading form of cancer in a few well-defined populations, including natives of southern China, Southeast Asia, the Arctic, and the Middle East/North Africa. The distinctive racial/ethnic and geographic distribution of NPC worldwide suggests that both environmental factors and genetic traits contribute to its development. This review aims to summarize the current knowledge regarding the epidemiology of NPC and to propose new avenues of research that could help illuminate the causes and ultimately the prevention of this remarkable disease. Well-established risk factors for NPC include elevated antibody titers against the Epstein-Barr virus, consumption of salt-preserved fish, a family history of NPC, and certain human leukocyte antigen class I genotypes. Consumption of other preserved foods, tobacco smoking, and a history of chronic respiratory tract conditions may be associated with elevated NPC risk, whereas consumption of fresh fruits and vegetables and other human leukocyte antigen genotypes may be associated with decreased risk. Evidence for a causal role of various inhalants, herbal medicines, and occupational exposures is inconsistent. Other than dietary modification, no concrete preventive measures for NPC exist. Given the unresolved gaps in understanding of NPC, there is a clear need for large-scale, population-based molecular epidemiologic studies to elucidate how environmental, viral, and genetic factors interact in both the development and the prevention of this disease. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1765–77)

The non‐Hodgkin lymphomas: A review of the epidemiologic literature

The non‐Hodgkin lymphomas (NHL) are a heterogeneous group of B‐cell and T‐cell neoplasms that arise primarily in the lymph nodes. NHL incidence rates in the US doubled between about 1970 and 1990, and stabilized during the 1990s. NHL accounts for ∼3.4% of cancer deaths in the US. Although some of the observed patterns in NHL have been related to HIV/AIDS, these conditions cannot fully explain the magnitude of the changes; neither do changes in classification systems nor improved diagnostic capabilities. Studies of occupational and environmental exposures (e.g., pesticides, solvents) have produced no consistent pattern of significant positive associations. Inverse associations with ultraviolet radiation exposure and alcohol and fish intake, and positive associations with meat and saturated fat intake have been reported in several studies; additional studies are needed to confirm or refute these associations. Family history of NHL or other hematolymphoproliferative cancers and personal history of several autoimmune disorders are associated with increased risk of NHL, but are not likely to account for a large proportion of cases. HIV and other infectious agents, such as human herpesvirus 8 and Epstein–Barr, appear to be associated with differing types of NHL, such as some B‐cell lymphomas. Future epidemiologic studies should evaluate associations by NHL type, enhance exposure information collected, and elucidate factors that may identify susceptible (or resistant) subpopulations because of genetic, immunologic or other characteristics. The extent to which the etiology of NHL types may differ is important to resolve in ongoing and future studies.

Why we should routinely screen Asian American adults for hepatitis B: A cross‐sectional study of Asians in California

Chronic hepatitis B virus (HBV) infection is a serious liver disease that, if left undiagnosed or without appropriate medical management, is associated with a 25% chance of death from cirrhosis or liver cancer. To study the demographics and prevalence of chronic HBV infection and HBV vaccination in the Asian American population, we provided free HBV serological screening and administered a survey to 3163 Asian American adult volunteers in the San Francisco Bay Area between 2001 and 2006. Of those screened, 8.9% were chronically infected with HBV. Notably, one‐half to two‐thirds (65.4%) of the chronically infected adults were unaware that they were infected. Of those who were not chronically infected, 44.8% lacked protective antibodies against HBV and were likely susceptible to future infection. Men were twice as likely as women to be chronically infected (12.1% versus 6.4%). Asian Americans born in East Asia, Southeast Asia, or the Pacific Islands were 19.4 times more likely to be chronically infected than those born in the United States. Self‐reporting of prior vaccination was unreliable to assess protection against HBV. Among the 12% who reported having been vaccinated, 5.2% were chronically infected, and 20.3% lacked protective antibodies. Conclusion: Given the high prevalence of unrecognized chronic HBV infection in the Asian American population, we call for healthcare providers to routinely screen Asian adults for HBV, regardless of their vaccination status. Those who test positive should be provided with culturally appropriate information to prevent disease transmission and proper medical management to reduce their risk of liver disease. (HEPATOLOGY 2007.)

Long-Term Exposure to Air Pollution and Cardiorespiratory Disease in the California Teachers Study Cohort

RATIONALE Several studies have linked long-term exposure to particulate air pollution with increased cardiopulmonary mortality; only two have also examined incident circulatory disease. OBJECTIVES To examine associations of individualized long-term exposures to particulate and gaseous air pollution with incident myocardial infarction and stroke, as well as all-cause and cause specific mortality. METHODS We estimated long-term residential air pollution exposure for more than 100,000 participants in the California Teachers Study, a prospective cohort of female public school professionals.We linked geocoded residential addresses with inverse distance-weighted monthly pollutant surfaces for two measures of particulate matter and for several gaseous pollutants. We examined associations between exposure to these pollutants and risks of incident myocardial infarction and stroke, and of all-cause and cause-specific mortality, using Cox proportional hazards models. MEASUREMENTS AND MAIN RESULTS We found elevated hazard ratios linking long-term exposure to particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5), scaled to an increment of 10 μg/m3 with mortality from ischemic heart disease (IHD) (1.20; 95% confidence interval [CI], 1.02-1.41) and, particularly among postmenopausal women, incident stroke (1.19; 95% CI, 1.02-1.38). Long-term exposure to particulate matter less than 10 μm in aerodynamic diameter (PM10) was associated with elevated risks for IHD mortality (1.06; 95% CI, 0.99-1.14) and incident stroke (1.06; 95% CI, 1.00-1.13), while exposure to nitrogen oxides was associated with elevated risks for IHD and all cardiovascular mortality. CONCLUSIONS This study provides evidence linking long-term exposure to PM2.5 and PM10 with increased risks of incident stroke as well as IHD mortality; exposure to nitrogen oxides was also related to death from cardiovascular diseases.

A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 ( REL ), 8q24.21 and 10p14 ( GATA3 )

To identify susceptibility loci for classical Hodgkins lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.

Genome-wide association study of follicular lymphoma identifies a risk locus at 6p21.32

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 × 10−29 and rs7755224, combined P = 2.00 × 10−19; r2 = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 × 10−9).

Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis

BACKGROUND Previous epidemiological studies of the relation between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) have been inconsistent, probably because of small sample sizes of individual studies that result from stratification by NHL subtype and type of alcoholic beverage. We aimed to assess the role of alcohol consumption in NHL with sufficient sample size to analyse by both type of alcoholic beverage and disease subtype. METHODS We obtained original data from nine case-control studies from the USA, UK, Sweden, and Italy in the International Lymphoma Epidemiology Consortium (InterLymph), yielding a pooled study population of 15 175 individuals (6492 cases and 8683 controls). We derived odds ratios (OR) and 95% CI from unconditional logistic regression models, controlling for study centre and other confounding factors. Heterogeneity between studies was assessed by comparison of results from joint fixed-effects logistic regression and two-stage random-effects logistic regression, and by calculation of Wald chi(2) statistics. FINDINGS People who drank alcohol had a lower risk of NHL than did non-drinkers (OR 0.83 [95% CI 0.76-0.89]). Compared with non-drinkers, risk estimates were lower for current drinkers than for former drinkers (0.73 [0.64-0.84] vs 0.95 [0.80-1.14]), but risk did not decrease with increasing alcohol consumption. The protective effect of alcohol did not vary by beverage type, but did change with NHL subtype. The lowest risk estimates were recorded for Burkitts lymphoma (0.51 [0.33-0.77]). INTERPRETATION People who drink alcoholic beverages might have a lower risk of NHL than those who do not, and this risk might vary by NHL subtype. Further study designs are needed to determine whether confounding lifestyle factors or immunomodulatory effects of alcohol explain this association.

Dietary Phytoestrogen, Serum Enterolactone and Risk of Prostate Cancer: The Cancer Prostate Sweden Study (Sweden)

ObjectiveBased on evidence that phytoestrogens may protect against prostate cancer, we evaluated the associations between serum enterolactone concentration or dietary phytoestrogen intake and risk of prostate cancer.MethodsIn our Swedish population-based case-control study, questionnaire-data were available for 1,499 prostate cancer cases and 1,130 controls, with serum enterolactone levels in a sub-group of 209 cases and 214 controls. Unconditional logistic regression was performed to estimate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with risk of prostate cancer.ResultsHigh intake of food items rich in phytoestrogens was associated with a decreased risk of prostate cancer. The OR comparing the highest to the lowest quartile of intake was 0.74 (95% CI: 0.57–0.95; p-value for trend: 0.01). In contrast, we found no association between dietary intake of total or individual lignans or isoflavonoids and risk of prostate cancer. Intermediate serum levels of enterolactone were associated with a decreased risk of prostate cancer. The ORs comparing increasing quartiles of serum enterolactone concentration to the lowest quartile were, respectively, 0.28 (95% CI: 0.15–0.55), 0.63 (95% CI: 0.35–1.14) and 0.74 (95% CI: 0.41–1.32).ConclusionsOur results support the hypothesis that certain foods high in phytoestrogens are associated with a lower risk of prostate cancer.

Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism

Dietary intake of marine fatty acids from fish may protect against prostate cancer development. We studied this association and whether it is modified by genetic variation in cyclooxygenase (COX)‐2, a key enzyme in fatty acid metabolism and inflammation. We assessed dietary intake of fish among 1,499 incident prostate cancer cases and 1,130 population controls in Sweden. Five single nucleotide polymorphisms (SNPs) were identified and genotyped in available blood samples for 1,378 cases and 782 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. Multiplicative and additive interactions between fish intake and COX‐2 SNPs on prostate cancer risk were evaluated. Eating fatty fish (e.g., salmon‐type fish) once or more per week, compared to never, was associated with reduced risk of prostate cancer (OR: 0.57, 95% CI: 0.43–0.76). The OR comparing the highest to the lowest quartile of marine fatty acids intake was 0.70 (95% CI: 0.51–0.97). We found a significant interaction (p < 0.001) between salmon‐type fish intake and a SNP in the COX‐2 gene (rs5275: +6365 T/C), but not with the 4 other SNPs examined. We found strong inverse associations with increasing intake of salmon‐type fish among carriers of the variant allele (OR for once per week or more vs. never = 0.28, 95% CI: 0.18–0.45; ptrend < 0.01), but no association among carriers of the more common allele. Frequent consumption of fatty fish and marine fatty acids appears to reduce the risk of prostate cancer, and this association is modified by genetic variation in the COX‐2 gene.

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.