Lindsay M. Morton

Prior medical conditions and medication use and risk of non-Hodgkin lymphoma in connecticut United States women

AbstractObjective: To further investigate the role of prior medical conditions and medication use in the etiology of non-Hodgkin lymphoma (NHL), we analyzed the data from a population-based case–control study of NHL in Connecticut women. Methods: A total of 601 histologically confirmed incident cases of NHL and 717 population-based controls were included in this study. In-person interviews were administered using standardized, structured questionnaires to collect information on medical conditions and medication use. Results: An increased risk was found among women who had a history of autoimmune disorders (such as rheumatoid arthritis, lupus erythematosus, Sjogrens syndrome, and multiple sclerosis), anemia, eczema, or psoriasis. An increased risk was also observed among women who had used steroidal anti-inflammatory drugs and tranquilizers. A reduced risk was found for women who had scarlet fever or who had used estrogen replacement therapy, aspirin, medications for non-insulin dependent diabetes, HMG-CoA reductase inhibitors, or beta-adrenergic blocking agents. Risk associated with past medical history appeared to vary based on NHL subtypes, but the results were based on small number of exposed subjects. Conclusion: A relationship between certain prior medical conditions and medication use and risk of NHL was observed in this study. Further studies are warranted to confirm our findings.

Cigarette Smoking and Risk of Non-Hodgkin Lymphoma: A Pooled Analysis from the International Lymphoma Epidemiology Consortium (InterLymph)

Background: The International Lymphoma Epidemiology Consortium (InterLymph) provides an opportunity to analyze the relationship between cigarette smoking and non-Hodgkin lymphoma with sufficient statistical power to consider non-Hodgkin lymphoma subtype. The results from previous studies of this relationship have been inconsistent, likely due to the small sample sizes that arose from stratification by disease subtype. To clarify the role of cigarette smoking in the etiology of non-Hodgkin lymphoma, we conducted a pooled analysis of original patient data from nine case-control studies of non-Hodgkin lymphoma conducted in the United States, Europe, and Australia. Methods: Original data were obtained from each study and uniformly coded. Risk estimates from fixed-effects and two-stage random-effects models were compared to determine the impact of interstudy heterogeneity. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from unconditional logistic regression models, controlling for study center, age, sex, and race. Results: In our pooled study population of 6,594 cases and 8,892 controls, smoking was associated with slightly increased risk estimates (OR, 1.07; 95% CI, 1.00-1.15). Stratification by non-Hodgkin lymphoma subtype revealed that the most consistent association between cigarette smoking and non-Hodgkin lymphoma was observed among follicular lymphomas (n = 1452). Compared with nonsmokers, current smokers had a higher OR for follicular lymphoma (1.31; 95% CI, 1.12-1.52) than former smokers (1.06; 95% CI, 0.93-1.22). Current heavy smoking (≥36 pack-years) was associated with a 45% increased OR for follicular lymphoma (1.45; 95% CI, 1.15-1.82) compared with nonsmokers. Conclusions: Cigarette smoking may increase the risk of developing follicular lymphoma but does not seem to affect risk of the other non-Hodgkin lymphoma subtypes we examined. Future research is needed to determine the biological mechanism responsible for our subtype-specific results.

Differences in incidence and trends of haematological malignancies in Japan and the United States

The incidence of a malignant disease reflects the genetic and cumulative exposure to the environment of a population. Therefore, evaluation of the incidence and trends of a disease in different populations may provide insights into its aetiology and pathogenesis. To evaluate the incidence of haematological malignancies according to specific subtypes, we used population‐based registry data in Japan (N = 125 148) and the United States (US; N = 172 925) from 1993 to 2008. The age‐adjusted incidence of haematological malignancies in Japan was approximately one‐half that in the US but has been increasing significantly, whereas no significant change was seen in the US [annual percent change (95% C confidence interval): Japan, +2·4% (1·7, 3·1); US, +0·1% (−0·1, 0·2)]. Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) showed the largest differences in incidence, with the most remarkable differences observed for chronic lymphocytic leukaemia, HL‐nodular sclerosis, mycosis fungoides and cutaneous T‐cell lymphoma. HL and NHL are increasing substantially in Japan but not in the US, suggesting that environmental exposures, such as Westernization of the life style may be causing this increase. Differences in the incidence and trends for specific subtypes also showed a marked contrast across subtypes, which, in turn, may provide significant new insights into disease aetiology in the future.

Autoimmune disease and subsequent risk of developing alimentary tract cancers among 4.5 million US male veterans

Autoimmunity is clearly linked with hematologic malignancies, but less is known about autoimmunity and alimentary tract cancer risk, despite the specific targeting of alimentary organs and tissues by several autoimmune diseases. The authors therefore conducted the first systematic evaluation of a broad range of specific autoimmune diseases and risk for subsequent alimentary tract cancer.

The Epidemic of Non-Hodgkin Lymphoma in the United States: Disentangling the Effect of HIV, 1992–2009

Background: For decades, non–Hodgkin lymphoma (NHL) incidence has been increasing worldwide. NHL risk is strongly increased among HIV-infected people. Our understanding of trends in NHL incidence has been hampered by difficulties in separating HIV-infected NHL cases from general population rates. Methods: NHL incidence data during 1992–2009 were derived from 10 U.S. SEER cancer registries with information on HIV status at NHL diagnosis. The CDC estimated the number of people living with HIV in the registry areas. The proportion of NHL cases with HIV and NHL rates in the total and the HIV-uninfected populations were estimated. Time trends were assessed with Joinpoint analyses. Results: Of 115,643 NHL cases diagnosed during 1992–2009, 5.9% were HIV-infected. The proportions of NHL cases with HIV were highest for diffuse large B-cell (DLBCL; 7.8%), Burkitt (26.9%), and peripheral T-cell lymphomas (3.2%) with low proportions (≤1.1%) in the other subtypes. NHL rates in the total population increased 0.3% per year during 1992–2009. However, rates of NHL in HIV-uninfected people increased 1.4% per year during 1992–2003, before becoming stable through 2009. Similar trends were observed for DLBCLs and follicular lymphoma in HIV-uninfected people; rates increased 2.7% per year until 2003 and 1.7% per year until 2005, respectively, before stabilizing. Conclusions: NHL incidence rates in the United States have plateaued over the last 5–10 years, independent of HIV infection. Impact: Although the causes of the long-term increase in NHL incidence rates in the United States remain unknown, general population rates of NHL have stabilized since the early 2000s, independent of HIV. Cancer Epidemiol Biomarkers Prev; 22(6); 1069–78. ©2013 AACR.

A prospective investigation of serum 25-hydroxyvitamin D and risk of lymphoid cancers

Studies indicate that higher sun exposure, especially in the recent past, is associated with reduced risk of non‐Hodgkin lymphoma (NHL). Ultraviolet radiation‐derived vitamin D may be protective against lymphomagenesis. We examined the relationship between prediagnostic serum 25‐hydroxyvitamin D (25(OH)D) and lymphoid cancer risk in a case–control study nested within the Alpha‐Tocopherol Beta‐Carotene Cancer Prevention Study cohort (1985–2002) of 29,133 Finnish male smokers (ages 50–69). We identified 270 incident lymphoid cancer cases and matched them individually with 538 controls by birth‐year and month of fasting blood draw at baseline. In conditional logistic regression models for 10 nmol/L increments or tertile comparisons, serum 25(OH)D was not associated with the risk of overall lymphoid cancers, NHL (n = 208) or multiple myeloma (n = 41). Odds ratios (OR) for NHL for higher tertiles were 0.75 (95% confidence interval (CI), 0.50, 1.14) and 0.82 (95% CI, 0.53, 1.26). The 25(OH)D‐NHL association, however, differed by follow‐up duration at diagnosis. Cases diagnosed less than 7 years from the baseline showed an inverse association (OR for highest vs. lowest tertile = 0.43; 95% CI: 0.23, 0.83; p for trend = 0.01), but not later diagnoses (OR = 1.52; 95% CI: 0.82, 2.80; p for trend = 0.17). The inverse association found for close exposure to diagnosis was not confounded by other risk factors for lymphoma or correlates of 25(OH)D. Although our findings suggest that circulating 25(OH)D is not likely associated with overall lymphoid cancer, they indicate a potentially protective effect on short‐term risk of NHL.

Cigarette smoking and risk of non-Hodgkin lymphoma subtypes among women

Previous studies of the relationship between cigarette smoking and non-Hodgkin lymphoma (NHL) have yielded conflicting results, perhaps because most studies have evaluated the risk for all NHL subtypes combined. Data from a population-based case–control study conducted among women in Connecticut were used to evaluate the impact of cigarette smoking on the risk of NHL by histologic type, tumour grade, and immunologic type. A total of 601 histologically confirmed, incident cases of NHL and 718 population-based controls provided in-person interviews. A standardised, structured questionnaire was used to collect information on each subjects current smoking status, age at initiation, duration and intensity of smoking, and cumulative lifetime exposure to smoking. Our data suggest that cigarette smoking does not alter the risk of all NHL subtypes combined. However, increased risk of follicular lymphoma appears to be associated with increased intensity and duration of smoking, and cumulative lifetime exposure to smoking. Compared with nonsmokers, women with a cumulative lifetime exposure of 16–33 pack-years and 34 pack-years or greater experience 50% increased risk (OR=1.5, 95% CI 0.9–2.5) and 80% increased risk (OR=1.8, 95% CI 1.1–3.2), respectively, of follicular lymphoma (P for linear trend=0.05). Our study findings are consistent with several previous epidemiologic studies suggesting that cigarette smoking increases the risk of follicular lymphoma. This research highlights the importance of distinguishing between NHL subtypes in future research on the aetiology of NHL.

Alcohol use and risk of non-Hodgkin's lymphoma among Connecticut women (United States).

Objective: Incidence rates of non-Hodgkins lymphoma (NHL) have risen dramatically over the past several decades; however, the etiology of NHL remains largely unknown. Previous studies of the relationship between alcohol consumption and NHL have yielded conflicting results. Data from a population-based case–control study among women in Connecticut were analyzed to determine the potential impact of alcohol consumption on risk of NHL. Methods: The study included 601 histologically confirmed, incident cases of NHL and 718 population-based controls. In-person interviews were administered using standardized, structured questionnaires to collect data on history of consumption for beer, wine, and liquor. Results: When compared to non-drinkers, women who reported consumption of at least 12 drinks per year of any type of alcohol experienced slightly reduced risk of NHL (OR: 0.82; 95% CI: 0.65–1.04). Further stratification by alcohol type revealed that the inverse association was mainly limited to wine consumption (OR: 0.75; 95% CI: 0.59–0.96), with no clear association for beer or liquor consumption. Risk of NHL was further reduced with increasing duration of wine consumption (p for linear trend = 0.02). Consumption of wine for greater than 40 years was associated with approximately 40% reduction in risk (OR: 0.63; 95% CI: 0.44–0.91). Conclusion: Our results are consistent with several recent epidemiologic studies that have also suggested an inverse association between wine consumption and risk of NHL. The reduction in risk of NHL associated with increased duration of wine consumption warrants further investigation in other populations.

Incidence of lymphoid neoplasms by subtype among six Asian ethnic groups in the United States, 1996-2004

ObjectivesTo establish baseline data for lymphoid neoplasm incidence by subtype for six Asian-American ethnic groups.MethodsIncident rates were estimated by age and sex for six Asian ethnic groups—Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Vietnamese—in five United States cancer registry areas during 1996–2004. For comparison, rates for non-Hispanic Whites were also estimated.ResultsDuring 1996–2004, Filipinos had the highest (24.0) and Koreans had the lowest incidence (12.7) of total lymphoid neoplasms. By subtype, Vietnamese and Filipinos had the highest incidence for diffuse large B-cell lymphoma (DLBCL) (8.0 and 7.2); Japanese had the highest incidence of follicular lymphoma (2.3). Although a general male predominance of lymphoid neoplasms was observed, this pattern varied by lymphoid neoplasm subtype. Whites generally had higher rates than all Asian ethnic groups for all lymphoid neoplasms and most lymphoma subtypes, although the magnitude of the difference varied by both ethnicity and lymphoma subtype.ConclusionsThe observed variations in incidence patterns among Asian ethnic groups in the United States suggest that it may be fruitful to pursue studies that compare Asian populations for postulated environmental and genetic risk factors.

The rising incidence of second cancers: patterns of occurrence and identification of risk factors for children and adults.

As the population of cancer survivors has increased and continues to age, the occurrence of second cancers has risen dramatically-from 9% of all cancer diagnoses in 1975-1979 to 19% in 2005-2009. The Childhood Cancer Survivor Study, a cohort of more than 14,000 childhood cancer survivors with detailed exposure data and long-term follow-up, has substantially contributed to our understanding of the roles of radiotherapy and chemotherapy in second cancer occurrence. In particular, dose-related risks have been demonstrated for second cancers of the breast, thyroid, central nervous system, gastrointestinal tract, and sarcomas following radiation. Cytotoxic chemotherapy-which has long been known to be leukemogenic-also appears to contribute to risk for a range of other second cancer types. Individuals who develop a second cancer are at particularly high risk for developing additional second cancers. A genome-wide association study of survivors of Hodgkin lymphoma who received radiotherapy identified a locus on chromosome 6q21 as being associated with second cancer risk, demonstrating that recent advances in genomics are likely to prove invaluable for elucidating the contribution of genetic susceptibility to second cancer etiology. Among adults, risk of second cancers varies substantially by type of first and second cancer, patient age, and prevalence of second cancer risk factors, including primary cancer treatments, environmental and lifestyle exposures, and genetic susceptibility. Further research is needed to quantify second cancer risks associated with specific etiologic factors and to identify the patients at highest risk of developing a second cancer to target prevention and screening efforts.