Risk of non-Hodgkin lymphoma after radiotherapy for solid cancers.
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ABSTRACT:
SUBMITTER: Kim CJ
PROVIDER: S-EPMC3862256 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
Publications
Risk of non-Hodgkin lymphoma after radiotherapy for solid cancers.
Kim Clara J CJ Freedman D Michal DM Curtis Rochelle E RE Berrington de Gonzalez Amy A Morton Lindsay M LM
Leukemia & lymphoma 20121231 8
Abstract Ionizing radiation increases risk for acute leukemia, but less is known about radiation and risk of other hematologic malignancies such as non-Hodgkin lymphoma (NHL). We compared second primary NHL incidence among patients who did and did not receive initial radiotherapy for first primary solid malignancy during 1981-2007 reported in nine Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries. We identified 5590 second NHL cases among 1 450 962 1-y ...[more]
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Project description:Infectious etiologies have been hypothesized for Hodgkin and non-Hodgkin lymphoma (HL and NHL) in early life, but findings to date for specific lymphomas and periods of susceptibility are conflicting. We conducted the first national cohort study to examine whether season of birth, a proxy for infectious exposures in the first few months of life, is associated with HL or NHL in childhood through young adulthood. A total of 3,571,574 persons born in Sweden in 1973-2008 were followed up through 2009 to examine the association between season of birth and incidence of HL (943 cases) or NHL (936 cases). We found a sinusoidal pattern in NHL risk by season of birth (p?=?0.04), with peak risk occurring among birthdates in April. Relative to persons born in fall (September-November), odds ratios for NHL by season of birth were 1.25 [95% confidence interval (CI), 1.04-1.50; p?=?0.02] for spring (March-May), 1.22 (95% CI, 1.01-1.48; p?=?0.04) for summer (June-August) and 1.11 (95% CI, 0.91-1.35; p?=?0.29) for winter (December-February). These findings did not vary by sex, age at diagnosis or major subtypes. In contrast, there was no seasonal association between birthdate and risk of HL (p?=?0.78). In this large cohort study, birth in spring or summer was associated with increased risk of NHL (but not HL) in childhood through young adulthood, possibly related to immunologic effects of delayed infectious exposures compared with fall or winter birth. These findings suggest that immunologic responses in early infancy may play an important role in the development of NHL.
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Project description:Non-Hodgkin lymphoma (NHL) represents a group of heterogeneous diseases that significantly vary in their causes, molecular profiles, and natural progression. In 2007, there will be approximately 59,000 newly diagnosed NHL cases in the United States and over 300,000 cases worldwide. Although new therapeutic regimens are minimizing the number of deaths related to NHL, causes for the majority of lymphomas remain undetermined. Recent studies suggest that dietary factors may contribute to the rising rates of NHL. This review will summarize epidemiologic reports that have studied the relationship between obesity, physical activity, and diet and risk of NHL. Based on a number of case-control and prospective cohort studies, overweight/obesity probably increases the risk of NHL, whereas moderate physical activity may reduce risk. Several studies support an inverse association between intakes of vegetables and NHL risk, particularly for the consumption of cruciferous vegetables. This may relate to the induction of apoptosis and growth arrest in preneoplastic and neoplastic cells, two important actions of isothiocyanates found in cruciferous vegetables. Studies also suggest that fish intake may be inversely associated with risk of NHL, although findings have not been entirely consistent. This may relate to the high organochlorine content in some fish that could override a protective effect. High consumption of fats, meat, and dairy products also may increase lymphoma risk. The accumulated scientific evidence concerning the associations between obesity, diet, and NHL suggests several identified modifiable risk factors that might be recommended to decrease lymphoma risk.
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Project description:Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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Project description:ImportanceResearch suggests that increased mitochondrial DNA copy number (mtDNAcn) is associated with increased risk of non-Hodgkin lymphoma (NHL); however, no studies to date have evaluated whether the mitochondrial DNA fraction with breaks (mtDNAfb) is associated with risk of NHL.ObjectiveTo evaluate the association of mtDNAfb with NHL risk.Design, setting, and participantsThis nested case-control study, which used prospectively collected samples as part of baseline enrollment (from 1985 through 1988) of 29 133 men who smoked for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study conducted in southwest Finland, included 107 incident NHL cases and 107 controls (matched on date of birth ±5 years). Analyses were conducted from January to September 2022.ExposureHigh-throughput real-time polymerase chain reaction assays quantifying mtDNAfb.Main outcomes and measuresIncident NHL cases were identified in the ATBC Study through April 30, 2002, using the Finnish Cancer Registry and the Register of Causes of Death. The mtDNAfb was quantified and categorized based on the median, tertile, and quartile distributions among controls. Odds ratios (ORs) and 95% CIs were estimated using conditional logistic regression models to assess the associations between categorized mtDNAfb and future risk of NHL, controlling for age, body mass index, number of cigarettes smoked per day, number of pack-years, and mtDNAcn.ResultsA total of 29 133 men (median [IQR] age, 57.2 [52.6-62.5] years) participated in ATBC Study. Higher mtDNAfb was associated with an increased risk of NHL (median OR, 2.89; 95% CI, 1.40-5.93) in a dose-dependent manner (quartile 2 vs 1 OR, 1.24; 95% CI, 0.43-3.40; quartile 3 vs 1 OR, 3.58; 95% CI, 1.39-9.24; quartile 4 vs 1 OR, 3.42; 95% CI, 1.30- 8.99; P = .004 for trend).Conclusions and relevanceThis study's findings suggest that increased mtDNAfb is associated with an increased future risk of NHL. Additional studies are needed to confirm these findings, particularly among women and nonsmokers.
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Project description:ObjectivesTo assess if excess absolute risk (EAR) of radiation-induced solid cancer can be used to rank radiotherapy plans for treatment of Hodgkin lymphoma (HL) in a statistically significant way.MethodsEAR models, calibrated with data from the Life Span Study and HL survivors, have been incorporated into a voxelised risk-calculation software, which is used to compare four treatment modalities planned for five virtual HL patients. Organ-specific parameters are generated repeatedly in a Monte Carlo fashion to model their uncertainties. This in turn enables a quantitative estimation of the EAR uncertainties.ResultsParameter-driven uncertainties on total EAR are around 13%, decreasing to around 2-5% for relative EAR comparisons. Total EAR estimations indicate that intensity modulated proton therapy decreases the average risk by 40% compared to the intensity modulated radiation therapy plan, 28% compared to the volumetric modulated arc therapy plan whereas the three-dimensional conformal radiation therapy plan is equivalent within the uncertainty.ConclusionRelative EAR is a useful metric for distinguishing between radiotherapy plans in terms of second cancer risk.Advances in knowledgeRelative EAR is not dominated by model or parameter uncertainties and can be used to guide the choice of radiotherapy for HL patients.
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Project description:BackgroundNon-Hodgkin lymphoma (NHL) comprises biologically and clinically heterogeneous subtypes. Previously, study size has limited the ability to compare and contrast the risk factor profiles among these heterogeneous subtypes.MethodsWe pooled individual-level data from 17 471 NHL cases and 23 096 controls in 20 case-control studies from the International Lymphoma Epidemiology Consortium (InterLymph). We estimated the associations, measured as odds ratios, between each of 11 NHL subtypes and self-reported medical history, family history of hematologic malignancy, lifestyle factors, and occupation. We then assessed the heterogeneity of associations by evaluating the variability (Q value) of the estimated odds ratios for a given exposure among subtypes. Finally, we organized the subtypes into a hierarchical tree to identify groups that had similar risk factor profiles. Statistical significance of tree partitions was estimated by permutation-based P values (P NODE).ResultsRisks differed statistically significantly among NHL subtypes for medical history factors (autoimmune diseases, hepatitis C virus seropositivity, eczema, and blood transfusion), family history of leukemia and multiple myeloma, alcohol consumption, cigarette smoking, and certain occupations, whereas generally homogeneous risks among subtypes were observed for family history of NHL, recreational sun exposure, hay fever, allergy, and socioeconomic status. Overall, the greatest difference in risk factors occurred between T-cell and B-cell lymphomas (P NODE < 1.0×10(-4)), with increased risks generally restricted to T-cell lymphomas for eczema, T-cell-activating autoimmune diseases, family history of multiple myeloma, and occupation as a painter. We further observed substantial heterogeneity among B-cell lymphomas (P NODE < 1.0×10(-4)). Increased risks for B-cell-activating autoimmune disease and hepatitis C virus seropositivity and decreased risks for alcohol consumption and occupation as a teacher generally were restricted to marginal zone lymphoma, Burkitt/Burkitt-like lymphoma/leukemia, diffuse large B-cell lymphoma, and/or lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.ConclusionsUsing a novel approach to investigate etiologic heterogeneity among NHL subtypes, we identified risk factors that were common among subtypes as well as risk factors that appeared to be distinct among individual or a few subtypes, suggesting both subtype-specific and shared underlying mechanisms. Further research is needed to test putative mechanisms, investigate other risk factors (eg, other infections, environmental exposures, and diet), and evaluate potential joint effects with genetic susceptibility.
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Project description:OBJECTIVE:Endotoxin, a component of the outer membrane of gram-negative bacteria, elicits a strong innate and inflammatory immune response associated with the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-?). Because TNF-? polymorphisms that increase TNF-? production are associated with an increased risk of non-Hodgkin lymphoma (NHL), we hypothesized that increased levels of household endotoxin would be associated with an increased NHL risk. METHODS:We evaluated this association in the National Cancer Institute/Surveillance, Epidemiology and End Results (NCI/SEER) NHL multicenter population-based case-control study. Used vacuum cleaner bags were collected from participants during a home interview. Dust samples from the bags of 594 cases and 442 controls were analyzed for endotoxin [endotoxin unit (EU)/mg of dust] using the kinetic chromogenic Limulus amebocyte lysate assay. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for age, sex, race, education, study center, and farm exposure. RESULTS:Endotoxin was not associated with NHL overall [odds ratio (OR) for highest quartile of endotoxin levels = 0.81, 95 % confidence interval (CI) = 0.55, 1.20; p for trend = 0.35] or with diffuse large B-cell lymphoma (OR = 0.63, 95 % CI = 0.34, 1.16; p = 0.31) or follicular lymphoma (OR = 1.07, 95 % CI = 0.61, 1.89; p = 0.73) subtypes. Both working and living on a farm were associated with higher household endotoxin levels compared to never working (p = 0.009) or living (p = 0.01) on a farm. Excluding farmers from the analysis did not change the results. CONCLUSIONS:We found no evidence of a role for household endotoxin in NHL etiology.
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