Ann Maree Hughes

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.

Personal sun exposure and risk of non Hodgkin lymphoma: A pooled analysis from the Interlymph Consortium

In 2004–2007 4 independent case‐control studies reported evidence that sun exposure might protect against NHL; a fifth, in women only, found increased risks of NHL associated with a range of sun exposure measurements. These 5 studies are the first to examine the association between personal sun exposure and NHL. We report here on the relationship between sun exposure and NHL in a pooled analysis of 10 studies participating in the International Lymphoma Epidemiology Consortium (InterLymph), including the 5 published studies. Ten case‐control studies covering 8,243 cases and 9,697 controls in the USA, Europe and Australia contributed original data for participants of European origin to the pooled analysis. Four kinds of measures of self‐reported personal sun exposure were assessed at interview. A two‐stage estimation method was used in which study‐specific odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for potential confounders including smoking and alcohol use, were obtained from unconditional logistic regression models and combined in random‐effects models to obtain the pooled estimates. Risk of NHL fell significantly with the composite measure of increasing recreational sun exposure, pooled OR = 0.76 (95% CI 0.63–0.91) for the highest exposure category (p for trend 0.01). A downtrend in risk with increasing total sun exposure was not statistically significant. The protective effect of recreational sun exposure was statistically significant at 18–40 years of age and in the 10 years before diagnosis, and for B cell, but not T cell, lymphomas. Increased recreational sun exposure may protect against NHL.

Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the InterLymph Consortium

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.

Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

BACKGROUND Accounting for 10%-15% of all non-Hodgkin lymphomas in Western populations, peripheral T-cell lymphomas (PTCL) are the most common T-cell lymphoma but little is known about their etiology. Our aim was to identify etiologic risk factors for PTCL overall, and for specific PTCL subtypes, by analyzing data from 15 epidemiologic studies participating in the InterLymph Consortium. METHODS A pooled analysis of individual-level data for 584 histologically confirmed PTCL cases and 15912 controls from 15 case-control studies conducted in Europe, North America, and Australia was undertaken. Data collected from questionnaires were harmonized to permit evaluation of a broad range of potential risk factors. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression. RESULTS Risk factors associated with increased overall PTCL risk with a P value less than .05 included: a family history of hematologic malignancies (OR = 1.92, 95% CI = 1.30 to 2.84); celiac disease (OR = 17.8, 95% CI = 8.61 to 36.79); eczema (OR = 1.41, 95% CI = 1.07 to 1.85); psoriasis (OR = 1.97, 95% CI = 1.17 to 3.32); smoking 40 or more years (OR = 1.92, 95% CI = 1.41 to 2.62); and employment as a textile worker (ever) (OR = 1.58, 95% CI = 1.05 to 2.38) and electrical fitter (ever) (OR = 2.89, 95% CI = 1.41 to 5.95). Exposures associated with reduced overall PTCL risk included a personal history of allergies (OR = 0.69, 95% CI = 0.54 to 0.87), alcohol consumption (ever) (OR = 0.64, 95% CI = 0.49 to 0.82), and having ever lived or worked on a farm (OR = 0.72, 95% CI = 0.55% to 0.95%). We also observed the well-established risk elevation for enteropathy-type PTCL among those with celiac disease in our data. Conclusions Our pooled analyses identified a number of new potential risk factors for PTCL and require further validation in independent series.

The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study.

To cite this article: Hughes AM, Lucas RM, Ponsonby A‐L, Chapman C, Coulthard A, Dear K, Dwyer T, Kilpatrick TJ, McMichael AJ, Pender MP, Taylor BV, Valery P, van der Mei IAF, Williams D. The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study. Pediatr Allergy Immunol 2011; 22: 327–333.

Epstein–Barr virus and multiple sclerosis

This review of the considerable evidence linking Epstein–Barr virus (EBV) infection to risk and disease progression in multiple sclerosis (MS) builds on the background to the virus and its interactions with the human host available in the online supplement (see supplement, available online only). The evidence for a similarity in the geographic patterns of occurrence of MS and EBV infection (with infectious mononucleosis or EBV specific serology used as surrogate markers), when reviewed critically, is very limited. There is strong evidence however that people with MS are more likely to report a past history of infectious mononucleosis (thought to represent initial EBV infection at an older age), and higher titres of EBV specific antibodies are associated with an increased risk of developing MS. Elevated levels of the latter are apparent many years before MS onset (compared with non-MS controls) and there is a dose–response relationship between MS risk and antibody titre, with antibodies to the EBV nuclear antigen-1 particularly important. The evidence in relation to EBV DNA load in blood or CSF is conflicting, as is that in relation to T cell responses to EBV. Several hypotheses that have been proposed to explain the links between EBV and MS risk are reviewed and gaps requiring further research are identified.

Risk of non-Hodgkin lymphoma associated with occupational exposure to solvents, metals, organic dusts and PCBs (Australia)

ObjectiveSeveral studies have suggested that there is an occupational component to the causation of non-Hodgkin lymphoma (NHL). We aimed to use accurate means to assess occupational exposures to solvents, metals, organic dusts and polychlorinated biphenyls (PCBs) in a case–control study.MethodsCases were incident NHLs during 2000 and 2001 in two regions of Australia. Controls were randomly selected from the electoral roll and frequency matched to cases by age, sex and region. A detailed occupational history was taken from each subject. For jobs with likely exposure to the chemicals of interest, additional questions were asked by telephone interview using modified job specific modules. An expert allocated exposures using the information in the job histories and the interviews. Odds ratios were calculated for each exposure adjusting for age, sex, region and ethnic origin.Results694 cases and 694 controls (70 and 45 respectively of those potentially eligible) participated. The risk of NHL was increased by about 30 for exposure to any solvent with a dose response relationship, subgroup analysis showed the finding was restricted to solvents other than benzene. Exposure to wood dust also increased the risk of NHL slightly. Exposures to other organic dusts, metals, and PCBs were not strongly related to NHL.ConclusionsThe risk of NHL appears to be increased by exposure to solvents other than benzene and possibly to wood dust.

Pigmentary characteristics, sun sensitivity and non‐Hodgkin lymphoma

We report on pigmentary characteristics, sun sensitivity and some other possible risk factors for non‐Hodgkin lymphoma (NHL) in people 20–74 years of age. A statewide case‐control study was conducted in New South Wales, Australia, with population‐based sampling of cases (n = 704) and controls (n = 694). Risk of NHL was increased in subjects with hazel eyes (OR = 1.48; 95% CI = 1.07–2.04), very fair skin (OR = 1.44; 95% CI = 1.01–2.07) and poor ability to tan (OR = 1.70; 95% CI = 1.06–2.71). Risk with mild facial freckling as a child (OR = 0.77; 95% CI = 0.59–0.99) was reduced relative to that with no or moderate to severe freckling. Smokers were not at increased risk of NHL. A past history of treatment for skin cancer was associated with a slight nonsignificant increase in risk. Previous radiotherapy and chemotherapy were associated with 1.5‐ to 2‐fold increases in risk but with wide confidence intervals. These results provide weak support for the possibility that sun sensitivity or perhaps sun exposure increases risk of NHL.

Allergy and risk of childhood leukaemia : Results from the UKCCS

We investigated the relationship between childhood leukaemia and preceding history of allergy. A nationwide case–control study of childhood cancers was conducted in the United Kingdom with population‐based sampling of cases (n = 839) and controls (n = 1,337), matched on age, sex and region of residence. Information about clinically diagnosed allergies was obtained from primary care records. More than a third of subjects had at least one allergy diagnosed prior to leukaemia diagnosis (cases) or pseudo‐diagnosis (controls). For both total acute lymphoblastic leukaemia (ALL) and common‐ALL/precursor B‐cell ALL (c‐ALL), a history of eczema was associated with a 30% significant reduction in risk: the odds ratios (OR) and 95% confidence intervals (CI) were 0.70 (0.51–0.97) and 0.68 (0.48–0.98), respectively. Similar associations were observed for hayfever (OR = 0.47; 95% CI: 0.26–0.85 and OR = 0.62; 95% CI: 0.33–1.16 for ALL and c‐ALL, respectively). No such patterns were seen either for asthma and ALL, or for any allergy and acute myeloid leukaemia. A comparative analysis of primary care records with parents recall of allergy revealed only moderate agreement with contemporaneous clinical diagnoses for both cases and controls—confirming the unreliability of parental report at interview. Our finding of a reciprocal relationship between allergy and ALL in children is compatible with the hypothesis that a dysregulated immune response is a critical determinant of childhood ALL.

WHO non-Hodgkin's lymphoma classification by criterion-based report review followed by targeted pathology review : An effective strategy for epidemiology studies

In a previous criterion-based pathology report review of 717 cases of non-Hodgkins lymphoma in an Australian population-based epidemiologic study, a WHO category could be assigned in 91% of cases, but confidence in this classification was high in only 57.5%. Given this lack of confidence, a pathology review was done in a subset of 315 cases, with the aims of assigning a WHO classification category and the corresponding International Classification of Diseases for Oncology, Third Edition code in all cases previously unclassified or classified with low confidence and testing the accuracy of report review in assigning a confident WHO classification. After pathology review, 10 cases were ineligible (not non-Hodgkins lymphoma, 3.2%) and 99% (301 of 305) of the remainder were assigned a WHO classification, with high confidence in 87% (261 of 301). There was 78% overall agreement between the WHO classification assigned by report review and pathology review, with 92% agreement when there was high confidence in the report review classification and 69% agreement when there was low confidence. Eighteen percent of follicular lymphomas and 23% of diffuse large B-cell lymphomas were reclassified. The pathology review increased the accuracy of WHO classification by an estimated 12.5% in the 694 cases who were still eligible in the study. Although a potential error rate of 7.5% remained, reviewing more cases, or not reviewing any cases classified with high confidence, would have produced only a small change in accuracy. Criterion-based pathology report review of all cases followed by selective pathology review in cases classified with low confidence is recommended as a cost-saving and accurate strategy for pathology review in large epidemiologic studies.