Occupational exposure to extremely low-frequency magnetic fields and follicular lymphoma risk: a family case-control study.

OBJECTIVES: We aimed to examine the relationship between occupational exposure to extremely low-frequency magnetic fields (ELF-MFs) and follicular lymphoma (FL) risk. METHODS: We conducted a family case-control study between 2011 and 2016 in Australia and included 681 cases. Controls were either a family member of cases (related (n=294), unrelated (n=179)) or were unrelated recruited for a similarly designed Australian multiple myeloma study (n=711). We obtained detailed job histories using lifetime work calendars. We assigned exposure to ELF-MFs using an enhanced job exposure matrix, with a lag period of 10 years. We examined associations with FL risk using logistic regression accounting for relatedness between cases and controls. We performed sensitivity analyses including by control type, by sex, complete case analyses, ELF-MF exposure percentiles in addition to quartiles, ELF-MF exposure in the maximum exposed job, a shorter lag period (1 year) and the cumulative exposure in the most recent time period (1-9 years). RESULTS: We observed no association with the average intensity, duration or lifetime cumulative exposure to occupational ELF-MF exposure in the primary or sensitivity analyses. CONCLUSIONS: Our findings do not support an association between occupational ELF-MF exposure and FL risk. Although the inclusion of family members as part of the larger control group may have biased our risk estimates towards the null, findings were similar in sensitivity analyses restricted to cases and unrelated controls. Further research incorporating enhanced exposure assessment to ELF-MF is warranted to inform occupational safety regulations and any potential role in lymphomagenesis.

Time trends in cancer incidence in Australian people living with HIV between 1982 and 2012.

OBJECTIVES: The aim of the study was to describe time trends in cancer incidence in people living with HIV (PLHIV) in Australia between 1982 and 2012. METHODS: A population-based prospective study was conducted using data linkage between the national HIV and cancer registries. Invasive cancers identified in PLHIV were grouped into AIDS-defining cancers (ADCs), infection-related non-ADCs (NADCs), and non-infection-related NADCs. Crude and age-standardized incidence rates of cancers were calculated and compared over five time periods: 1982-1995, 1996-1999, 2000-2004, 2005-2008 and 2009-2012, roughly reflecting advances in HIV antiretroviral therapy. Standardized incidence ratios (SIRs) compared with the Australian general population were calculated for each time period. Generalized linear models were developed to assess time trends in crude and age-standardized incidences. RESULTS: For ADCs, the crude and age-standardized incidences of Kaposi sarcoma and non-Hodgkin lymphoma substantially declined over time (P-trend < 0.001 for all) but SIRs remained significantly elevated. For infection-related NADCs, there were significant increases in the crude incidences of anal, liver and head and neck cancers. Age-standardized incidences increased for anal cancer (P-trend = 0.002) and liver cancer (P-trend < 0.001). SIRs were significantly elevated for anal cancer, liver cancer and Hodgkin lymphoma. For non-infection-related NADCs, the crude incidence of colorectal, lung and prostate cancers increased over time, but age-standardized incidences remained stable. CONCLUSIONS: Continuous improvements and high coverage of antiretroviral therapy have reduced the incidence of ADCs in PLHIV in Australia. Clinical monitoring of anal and liver cancers in people living with HIV should be performed, given the increasing incidence of these cancers.

A systematic review and meta-analysis of occupational exposures and risk of follicular lymphoma.

BACKGROUND: The etiology of follicular lymphoma (FL), a common non-Hodgkin lymphoma subtype, is largely unknown. OBJECTIVE: We performed a systematic review and meta-analysis of observational studies examining the relationship between occupational exposures and FL risk. METHODS: We searched Ovid MEDLINE, Ovid EMBASE, and Web of Science for eligible observational studies examining job titles or occupational exposures prior to January 1, 2020. We performed a narrative synthesis and used random-effects models to generate meta-estimates of relative risk (RR) with 95% confidence intervals (95%CI) for exposures reported by three or more studies. RESULTS: Fifty-eight studies were eligible. Ten cohort and 37 case-control studies quantified FL risk in relation to any exposure to one or more occupational groups or agents. Eight cohort and 19 case-control studies examined dose-response relationships. We found evidence of a positive association with increasing plasma concentration of dichlorodiphenyldichloroethylene (DDE; meta-RR = 1.51, 95%CI = 0.99, 2.31; I2 = 0.0%) and polychlorinated biphenyls (PCBs; meta-RR = 1.47, 95%CI = 0.97, 2.24; I2 = 8.6%). We observed a positive association with exposure to any solvent (meta-RR = 1.16, 95%CI = 1.00, 1.34; I2 = 0.0%) and chlorinated solvents (meta-RR = 1.35, 95%CI = 1.09, 1.68; I2 = 0.0%). Single studies reported a significant positive dose-response association for exposure to any pesticide, hexachlorobenzene, any organophosphate, diazinon, metolachlor, carbaryl, lindane, trichloroethylene, oils/greases, and extremely low-frequency magnetic fields. Job title-only analyses suggested increased risk for medical doctors and spray painters, and decreased risk for bakers and teachers. Overall, studies demonstrated low risk of bias, but most studies examined small numbers of exposed cases. CONCLUSIONS: Current evidence indicates a positive association between FL and occupational exposure to DDE, PCBs, any solvent and chlorinated solvents. Our findings may help guide policies and practices on the safe use of solvents and inform models of lymphomagenesis. Future studies with larger sample sizes and comprehensive quantitative exposure measures may elucidate other avoidable carcinogenic exposures.

Lifestyle and risk of follicular lymphoma: a systematic review and meta-analysis of observational studies.

PURPOSE: To investigate the relationship between follicular lymphoma (FL) risk and common modifiable lifestyle factors, specifically smoking, alcohol, body mass index (BMI), and hair dye use. METHODS: We performed a systematic review and meta-analysis of observational studies published prior to 01 January 2020. We searched Ovid MEDLINE, Ovid EMBASE, and Web of Science and the reference lists of original studies and review articles. We used random-effects models to generate meta-estimates of relative risk (RR) with 95% confidence intervals (95% CI). RESULTS: Twenty-four cohort and ten case-control studies were eligible. Ten articles examined smoking, 11 alcohol, 13 BMI, and four hair dye use and risk of FL. The meta-estimate for current smoking was 1.11 (95% CI 0.92-1.35; I2 = 51%) and there was no significant dose-response per 5-year increase in duration (p-trend = 0.087). Current alcohol intake was inversely associated with FL risk (meta-RR 0.87, 95% CI 0.81-0.94; I2 = 0%) and there was a significant dose-response per 5 drinks/week increase in intake (p-trend = 0.008). There was no association with 5 kg/m2 increase in early adulthood BMI (meta-RR 1.05, 95% CI 0.91-1.20; I2 = 7%) or being overweight (meta-RR 0.99, 95% CI 0.92-1.07; I2 = 0%) or obese (meta-RR 1.08, 95% CI 0.99-1.17; I2 = 0%) as an adult. Hair dye use before 1980 was positively associated with FL risk (meta-RR 1.66, 95% CI 1.22-2.25; I2 = 55%) and no evidence of effect after 1980. CONCLUSION: We found consistent evidence of an inverse association between current alcohol intake and FL risk, and a significant increased risk with hair dye use before 1980. The evidence for smoking is heterogeneous, but most studies did not support an association. Further research is required to understand the mechanisms underlying these associations and the potential for prevention strategies.

Lymphoid neoplasm incidence by WHO subtype in Australia 1982-2006.

There are limited data characterizing the subtype-specific incidence of lymphoid neoplasms in the World Health Organization (WHO) Classification era. Data were obtained on all incident lymphoid neoplasms registered in Australia during 1982-2006. Subtypes were grouped using the InterLymph nested hierarchical classification, based on the 2008 WHO Classification. Temporal trends were examined using Joinpoint regression; average annual percentage change in incidence was computed. Multiple Poisson regression was used to compare incidence by sex and age. The incidence of all non-Hodgkin lymphoma (NHL) increased by 2.5%/year during 1982-1996 and was stable thereafter. During 1997-2006, several mature B- and natural killer (NK)-/T-cell NHL subtypes increased in incidence, including diffuse large B-cell (1.3%/year), follicular (2.5%/year), Burkitt (6.8%/year), marginal zone (13.2%/year), mantle cell (4.2%/year), peripheral T-cell lymphoma (4.7%/year) and plasmacytoma (7.1%/year). While chronic lymphocytic leukemia incidence was stable, small lymphocytic lymphoma incidence declined (8.1%/year). Hodgkin lymphoma (HL) incidence increased during 1997-2006 (2.2%/year), both classical (4.3%/year) and nodular lymphocyte predominant (12.1%/year) HL. Diagnostic artifact, evidenced by a sustained decline in the incidence of NHL not otherwise specified (NOS; 5.8%/year) and lymphoid neoplasms NOS (5.6%/year), limits the interpretation of temporal trends for some subtypes. A marked male predominance was observed for almost all subtypes. Incidence of mature B- and NK-/T-cell NHL subtypes increased sharply with age, except for Burkitt lymphoma/leukemia. For HL subtypes, a bimodal age distribution was only evident for nodular sclerosis HL. Variation in incidence patterns over time and by sex and age supports etiological differences between lymphoid neoplasm subtypes.

A Population-Based Family Case-Control Study of Sun Exposure and Follicular Lymphoma Risk.

BACKGROUND: Epidemiologic evidence suggests an inverse association between sun exposure and follicular lymphoma risk. METHODS: We conducted an Australian population-based family case-control study based on 666 cases and 459 controls (288 related, 171 unrelated). Participants completed a lifetime residence and work calendar and recalled outdoor hours on weekdays, weekends, and holidays in the warmer and cooler months at ages 10, 20, 30, and 40 years, and clothing types worn in the warmer months. We used a group-based trajectory modeling approach to identify outdoor hour trajectories over time and examined associations with follicular lymphoma risk using logistic regression. RESULTS: We observed an inverse association between follicular lymphoma risk and several measures of high lifetime sun exposure, particularly intermittent exposure (weekends, holidays). Associations included reduced risk with increasing time outdoors on holidays in the warmer months [highest category OR = 0.56; 95% confidence interval (CI), 0.42-0.76; Ptrend < 0.01], high outdoor hours on weekends in the warmer months (highest category OR = 0.71; 95% CI, 0.52-0.96), and increasing time outdoors in the warmer and cooler months combined (highest category OR = 0.66; 95% CI, 0.50-0.91; Ptrend 0.01). Risk was reduced for high outdoor hour maintainers in the warmer months across the decade years (OR = 0.71; 95% CI, 0.53-0.96). CONCLUSIONS: High total and intermittent sun exposure, particularly in the warmer months, may be protective against the development of follicular lymphoma. IMPACT: Although sun exposure is not recommended as a cancer control policy, confirming this association may provide insights regarding the future control of this intractable malignancy.

Latitude gradients for lymphoid neoplasm subtypes in Australia support an association with ultraviolet radiation exposure.

Given the uncertainty surrounding solar ultraviolet radiation (UVR) exposure and risk of lymphoid neoplasms, we performed an ecological analysis of national Australian data for incident cases diagnosed between 2002 and 2006. Subtype-specific incidence was examined by latitude band (<29°S, 29-36°S, ≥37°S), a proxy for ambient UVR exposure, using multiple Poisson regression, adjusted for sex, age-group and calendar year. Incidence increased with distance from the equator for several mature B-cell non-Hodgkin lymphomas, including diffuse large B-cell [incidence rate ratio (IRR) = 1.37; 95% confidence interval (CI): 1.16-1.61 for latitude ≥37°S relative to <29°S], lymphoplasmacytic (IRR = 1.34; 95% CI: 1.12-1.61), mucosa-associated lymphoid tissue (IRR = 1.32; 95% CI: 0.97-1.80) and mantle cell lymphoma (IRR = 1.29; 95% CI: 1.05-1.58), as well as plasmacytoma (IRR = 1.52; 95% CI: 1.09-2.11) and plasma cell myeloma (IRR = 1.15; 95% CI: 1.03-1.27). A similar pattern was observed for several mature cutaneous T-cell neoplasms, including primary cutaneous anaplastic large cell lymphoma (IRR = 4.26; 95% CI: 1.85-9.84), mycosis fungoides/Sézary syndrome (IRR = 1.72; 95% CI: 1.20-2.46), and peripheral T-cell lymphoma not otherwise specified (NOS) (IRR = 1.53; 95% CI: 1.17-2.00). Incidence of mixed cellularity/lymphocyte-depleted (IRR = 1.60; 95% CI: 1.16-2.20) and nodular sclerosis Hodgkin lymphoma (IRR = 1.57; 95% CI: 1.33-1.85) also increased with distance from the equator. Many of these subtypes have a known association with infection or immune dysregulation. Our findings support a possible protective effect of UVR exposure on the risk of several lymphoid neoplasms, possibly through vitamin D-related immune modulation critical in lymphomagenesis.

Prevalence of Australians exposed to potentially cardiotoxic cancer medicines: a population-based cohort study.

Background: Cardiovascular disease (CVD) and cancer are leading causes of death and people with cancer are at higher risk of developing CVD than the general population. Many cancer medicines have cardiotoxic effects but the size of the population exposed to these potentially cardiotoxic medicines is not known. We aimed to determine the prevalence of exposure to potentially cardiotoxic cancer medicines in Australia. Methods: We identified potentially cardiotoxic systemic cancer medicines through searching the literature and registered product information documents. We conducted a retrospective cohort study of Australians dispensed potentially cardiotoxic cancer medicines between 2005 and 2021, calculating age-standardised annual prevalence rates of people alive with exposure to a potentially cardiotoxic medicine during or prior to each year of the study period. Findings: We identified 108,175 people dispensed at least one potentially cardiotoxic cancer medicine; median age, 64 (IQR: 52-74); 57% female. Overall prevalence increased from 49 (95%CI: 48.7-49.3)/10,000 to 232 (95%CI: 231.4-232.6)/10,000 over the study period; 61 (95%CI: 60.5-61.5)/10,000 to 293 (95%CI: 292.1-293.9)/10,000 for females; and 39 (95%CI: 38.6-39.4)/10,000 to 169 (95%CI: 168.3-169.7)/10,000 for males. People alive five years following first exposure increased from 29 (95%CI: 28.8-29.2)/10,000 to 134 (95%CI: 133.6-134.4)/10,000; and from 22 (95%CI: 21.8-22.2)/10,000 to 76 (95%CI: 75.7-76.3)/10,000 for those alive at least 10 years following first exposure. Most people were exposed to only one potentially cardiotoxic medicine, rates of which increased from 39 (95%CI: 38.7-39.3)/10,000 in 2005 to 131 (95%CI: 130.6-131.4)/10,000 in 2021. Interpretation: The number of people exposed to efficacious yet potentially cardiotoxic cancer medicines in Australia is growing. Our findings can support the development of service planning and create awareness about the magnitude of cancer treatment-related cardiotoxicities. Funding: NHMRC Centre for Research Excellence in Medicines Intelligence, Cancer Institute NSW Early Career Fellowship.

Second Primary Cancers in People With HIV/AIDS: A National Data Linkage Study of Incidence and Risk Factors.

BACKGROUND: Evidence regarding the characteristics of second primary cancer (SPC) in people living with HIV (PLWHIV) is limited. SETTING: We performed a national population-based data linkage study to determine the incidence and risk factors of SPC in PLWHIV in Australia between 1982 and 2012. METHODS: We conducted a probabilistic data linkage study to compare the incidence of SPC over time, defined using HIV treatment eras, for SPCs related to oncogenic viral infection in comparison with non-infection-related SPCs. Risk factors considered included age at diagnosis of cancer, sex, HIV exposure modality, and CD4 + count. RESULTS: Of 29,383 individuals diagnosed with HIV, 3123 individuals who developed a first primary cancer were included in the analysis. Among them, 229 cases of SPC were identified across 27,398 person-years of follow-up. The most common SPCs were non-Hodgkin lymphomas (n = 71, 31%). The incidence of SPC overall did not change over time; however, there was an increase in individuals diagnosed with HIV in later eras ( P trend =0.001). The incidence of non-infection-related SPC increased over time and was associated with older age ( P trend = 0.005) and the acquisition of HIV in later eras ( P trend <0.001). Conversely, the incidence of infection-related SPC decreased ( P trend <0.001), but this was no longer significant after adjustment for age ( P trend = 0.14). CONCLUSIONS: The risk of SPC in PLWHIV in Australia remains high, with a temporal increase observed in non-infection-related cancer, likely due to aging of the population. Optimal screening and prevention strategies for SPC in PLWHIV are increasingly important.

Modifiable lifestyle risk factors and survival after diagnosis with multiple myeloma.

BACKGROUND: While remaining incurable, median overall survival for MM now exceeds 5 years. Yet few studies have investigated how modifiable lifestyle factors influence survival. We investigate whether adiposity, diet, alcohol, or smoking are associated with MM-related fatality. RESEARCH DESIGN AND METHODS: We recruited 760 incident cases of MM via cancer registries in two Australian states during 2010-2016. Participants returned questionnaires on health and lifestyle. Follow-up ended in 2020. Flexible parametric survival models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for lifestyle exposures and risk of all-cause and MM-specific fatality. RESULTS: Higher pre-diagnosis Alternative Healthy Eating Index (AHEI) scores were associated with reduced MM-specific fatality (per 10-unit score, HR = 0.84, 95%CI = 0.70-0.99). Pre-diagnosis alcohol consumption was inversely associated with MM-specific fatality, compared with nondrinkers (0.1-20 g per day, HR = 0.59, 95%CI = 0.39-0.90; >20 g per day, HR = 0.67, 95%CI = 0.40-1.13). Tobacco smoking was associated with increased all-cause fatality compared with never smoking (former smokers: HR = 1.44, 95%CI = 1.10-1.88; current smokers: HR = 1.30, 95%CI = 0.80-2.10). There was no association between pre-enrollment body mass index (BMI) and MM-specific or all-cause fatality. CONCLUSIONS: Our findings support established recommendations for healthy diets and against smoking. Higher quality diet, as measured by the AHEI, may improve survival post diagnosis with MM.

Are antibody deficiency disorders associated with a narrower range of cancers than other forms of immunodeficiency?

Analysis of cancer risk in primary immune deficiency (PID) offers insight into the relationship between immune function and cancer. Data on Australian patients (n = 1132) notified voluntarily to the Australasian Society of Clinical Immunology and Allergy PID Registry (1990-2008) were linked with national death and cancer registries. Person-years of follow-up commenced from up to 15 years before registration on the PID Registry or January 1982, the inception of national cancer registration. Site-specific, 5-year age-, sex-, calendar year-, and state-standardized incidence ratios (SIRs) with 95% confidence intervals (95% CIs) were calculated for all cancers except nonmelanocytic skin cancer. During an average of 16 person-years follow-up, a 1.6-fold excess relative risk of cancer was observed (n = 58; SIR 1.60, 95% CI 1.22-2.07) for all PID combined. Relative risk was increased for non-Hodgkin lymphoma (n = 16; SIR 8.82, 95% CI 5.04-14.30), leukemia (n = 4; SIR 5.36, 95% CI 1.46-13.73), and stomach cancer (n = 3; SIR 6.10, 95% CI 1.26-17.84). Excess cancer risk was observed for predominantly antibody deficiencies and other well-defined immunodeficiency syndromes. Results suggest that predominantly antibody deficiencies may be associated with a narrower range of solid cancers than immunodeficiency characterized by predominantly T-cell deficiency, such as iatrogenic and HIV-related immunodeficiency, although this requires confirmation in larger cohorts.

Incidence and risk factors of hypertension therapy in Australian cancer patients treated with vascular signalling pathway inhibitors.

BACKGROUND: Clinical trials report systemic hypertension is an adverse effect of vascular signalling pathway inhibitor (VSPi) use. There are limited data from routine clinical practice. We aimed to estimate the real-world incidence and risk factors of new-onset and aggravated hypertension for cancer patients dispensed VSPi in whole-of-population Australian setting. METHODS: We used dispensing records for a 10% random sample of Australians to identify treatment with subsidised VSPi from 2013 to 2018. We further identified dispensings of oral antihypertensive medicines 6 months before and 12 months after VSPi therapy. We defined (i) new-onset hypertension in people first dispensed antihypertensives after VSPi and (ii) aggravated hypertension in people with prior antihypertensive use dispensed an additional, or higher strength, antihypertensive after VSPi. We applied the Fine-Gray cumulative incidence function and Cox proportional hazard regression. RESULTS: 1802 patients were dispensed at least one VSPi. The mean age of the cohort was 65 years and 57% were male. The incidence of new-onset treated hypertension was 24.3% (95%CI: 21.2-27.8); age ≥ 60 years (HR 1.74; 95%CI: 1.32-2.31) and treatment with oral tyrosine kinase inhibitors compared to bevacizumab (HR 1.96; 95%CI: 1.16-3.31) were risk factors. The incidence of aggravated hypertension was 25.2% (95%CI: 22.0-28.7) and risk was elevated for patients with renal cancer (HR 2.84; 95%CI: 1.49-5.41) and cancers other than colorectal (HR 1.85; 95%CI: 1.12-3.03). CONCLUSIONS: Our real-world estimates of incident hypertension appear comparable to those observed in clinical trials (21.6-23.6%). Our population-based study provides some insight into the burden of hypertension in patients commencing VSPi in routine practice.

Alcohol and tobacco use and risk of multiple myeloma: A case-control study.

Multiple myeloma (MM) is the second most common hematological cancer and causes significant mortality and morbidity. Knowledge regarding modifiable risk factors for MM remains limited. This analysis of an Australian population-based case-control family study investigates whether smoking or alcohol consumption is associated with risk of MM and related diseases. Incident cases (n = 789) of MM were recruited via cancer registries in Victoria and New South Wales. Controls (n = 1,113) were either family members of cases (n = 696) or controls recruited for a similarly designed study of renal cancers (n = 417). Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multivariable logistic regression. Heavy intake (>20 g ethanol/day) of alcohol had a lower risk of MM compared with nondrinkers (OR = 0.68, 95% CI: 0.50-0.93), and there was an inverse dose-response relationship for average daily alcohol intake (OR per 10 g ethanol per day = 0.92, 95% CI: 0.86-0.99); there was no evidence of an interaction with sex. There was no evidence of an association with MM risk for smoking-related exposures (p > 0.18). The associations between smoking and alcohol with MM are similar to those with non-Hodgkin lymphoma. Further research into potential underlying mechanisms is warranted.

Associations between Smoking and Alcohol and Follicular Lymphoma Incidence and Survival: A Family-Based Case-Control Study in Australia.

The association between smoking and alcohol consumption and follicular lymphoma (FL) incidence and clinical outcome is uncertain. We conducted a population-based family case-control study (709 cases: 490 controls) in Australia. We assessed lifetime history of smoking and recent alcohol consumption and followed-up cases (median = 83 months). We examined associations with FL risk using unconditional logistic regression and with all-cause and FL-specific mortality of cases using Cox regression. FL risk was associated with ever smoking (OR = 1.38, 95%CI = 1.08−1.74), former smoking (OR = 1.36, 95%CI = 1.05−1.77), smoking initiation before age 17 (OR = 1.47, 95%CI = 1.06−2.05), the highest categories of cigarettes smoked per day (OR = 1.44, 95%CI = 1.04−2.01), smoking duration (OR = 1.53, 95%CI = 1.07−2.18) and pack-years (OR = 1.56, 95%CI = 1.10−2.22). For never smokers, FL risk increased for those exposed indoors to >2 smokers during childhood (OR = 1.84, 95%CI = 1.11−3.04). For cases, current smoking and the highest categories of smoking duration and lifetime cigarette exposure were associated with elevated all-cause mortality. The hazard ratio for current smoking and FL-specific mortality was 2.97 (95%CI = 0.91−9.72). We found no association between recent alcohol consumption and FL risk, all-cause or FL-specific mortality. Our study showed consistent evidence of an association between smoking and increased FL risk and possibly also FL-specific mortality. Strengthening anti-smoking policies and interventions may reduce the population burden of FL.

Dietary intake of animal-based products and likelihood of follicular lymphoma and survival: A population-based family case-control study.

Background: The association between dietary intake of foods of animal origin and follicular lymphoma (FL) risk and survival is uncertain. In this study, we examined the relationship between dietary intake of dairy foods and fats, meat, fish and seafoods, and the likelihood of FL and survival. Methods: We conducted a population-based family case-control study in Australia between 2011 and 2016 and included 710 cases, 303 siblings and 186 spouse/partner controls. We assessed dietary intake of animal products prior to diagnosis (the year before last) using a structured food frequency questionnaire and followed-up cases over a median of 6.9 years using record linkage to national death data. We examined associations with the likelihood of FL using logistic regression and used Cox regression to assess association with all-cause and FL-specific mortality among cases. Results: We observed an increased likelihood of FL with increasing daily quantity of oily fish consumption in the year before last (highest category OR = 1.96, CI = 1.02-3.77; p-trend 0.06) among cases and sibling controls, but no associations with spouse/partner controls. We found no association between the likelihood of FL and the consumption of other types of fish or seafood, meats or dairy foods and fats. In FL cases, we found no association between meat or oily fish intake and all-cause or FL-specific mortality. Conclusion: Our study showed suggestive evidence of a positive association between oily fish intake and the likelihood of FL, but findings varied by control type. Further investigation of the potential role of environmental contaminants in oily fish on FL etiology is warranted.

Associations between early-life growth pattern and body size and follicular lymphoma risk and survival: a family-based case-control study.

BACKGROUND: The influence of early-life growth pattern and body size on follicular lymphoma (FL) risk and survival is unclear. In this study, we aimed to investigate the association between gestational age, growth during childhood, body size, changes in body shape over time, and FL risk and survival. METHODS: We conducted a population-based family case-control study and included 706 cases and 490 controls. We ascertained gestational age, growth during childhood, body size and body shape using questionnaires and followed-up cases (median=83 months) using record linkage with national death records. We used a group-based trajectory modeling approach to identify body shape trajectories from ages 5-70. We examined associations with FL risk using unconditional logistic regression and used Cox regression to assess the association between body mass index (BMI) and all-cause and FL-specific mortality among cases. RESULTS: We found no association between gestational age, childhood height and FL risk. We observed a modest increase in FL risk with being obese 5 years prior to enrolment (OR=1.43, 95 %CI=0.99-2.06; BMI ≥30 kg/m2) and per 5-kg/m2 increase in BMI 5 years prior to enrolment (OR=1.14, 95 %CI=0.99-1.31). The excess risk for obesity 5 years prior to enrolment was higher for ever-smokers (OR=2.00, 95 %CI=1.08-3.69) than never-smokers (OR=1.14, 95 %CI=0.71-1.84). We found no association between FL risk and BMI at enrolment, BMI for heaviest lifetime weight, the highest categories of adult weight or height, trouser size, body shape at different ages or body shape trajectory. We also observed no association between all-cause or FL-specific mortality and excess adiposity at or prior to enrolment. CONCLUSION: We observed a weak association between elevated BMI and FL risk, and no association with all-cause or FL-specific mortality, consistent with previous studies. Future studies incorporating biomarkers are needed to elucidate possible mechanisms underlying the role of body composition in FL etiology.

Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation.

Non-Hodgkin lymphoma (NHL) incidence is greatly increased after kidney transplantation. NHL risk was investigated in a nationwide cohort of 8164 kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry. NHL diagnoses were ascertained using linkage with national cancer registry records. Multivariate Poisson regression was used to compute incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing risk by transplant function, and risk factors for early (< 2 years) and late (>/= 2 years) NHL during the first transplantation. NHL occurred in 133 patients. Incidence was strikingly lower after transplant failure and cessation of immunosuppression than during transplant function (IRR, 0.25; 95% CI, 0.08-0.80; P = .019). Early NHL (n = 27) was associated with Epstein-Barr virus (EBV) seronegativity at transplantation (IRR, 4.66; 95% CI, 2.10-10.36, P < .001) and receipt of T cell-depleting antibodies (IRR, 2.39; 95% CI, 1.08-5.30; P = .031). Late NHL (n = 79) was associated with increasing year of age (IRR, 1.02; 95% CI, 1.01-1.04; P = .006), increasing time since transplantation (P < .001), and current use of calcineurin inhibitors (IRR, 3.13; 95% CI, 1.53-6.39; P = .002). These findings support 2 mechanisms of lymphomagenesis, one predominantly of primary EBV infection in the context of intense immunosuppression, and another of dysregulated lymphoid proliferation in a prolonged immunosuppressed state.

No excess risk of follicular lymphoma in kidney transplant and HIV-related immunodeficiency.

Subtype-specific incidence patterns in populations at high risk of lymphoma offer insight into lymphomagenesis. The incidence profiles for the 2 most common non-Hodgkin lymphoma subtypes were compared for 2 immunodeficient populations, adults receiving a kidney transplant 1982-2003 (n = 7,730) or diagnosed with human immunodeficiency virus (HIV) infection 1982-2004 (n = 17,175). National, population-based registries were linked and standardized incidence ratios (SIRs) were computed for each cohort and lymphoma subtype. Risk of diffuse large B-cell lymphoma was significantly increased after transplantation (SIR 17.83, 95% CI: 13.61-22.95) and after HIV infection (SIR 58.81, 95% CI: 52.59-65.56). Rates of follicular lymphoma (FL) were neither significantly increased nor decreased in transplant recipients (SIR 0.82, 95% CI: 0.10-2.96) and in people with HIV (SIR 1.25, 95% CI: 0.41-2.91). The findings argue against an infectious or other immunodeficiency-related etiology for FL and clearly differentiate it from diffuse large B-cell lymphoma.

Cardiovascular Toxicity of Targeted Therapies for Cancer: An Overview of Systematic Reviews.

BACKGROUND: Several targeted therapies for cancer have been associated with cardiovascular toxicity. The evidence for this association has not been synthesized systematically nor has the quality of evidence been considered. We synthesized systematic review evidence of cardiovascular toxicity of individual targeted agents. METHODS: We searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews for systematic reviews with meta-analyses of cardiovascular outcomes for individual agents published to May 2020. We selected reviews according to prespecified eligibility criteria (International Prospective Register of Systematic Reviews CRD42017080014). We classified evidence of cardiovascular toxicity as sufficient, probable, possible, or indeterminate for specific cardiovascular outcomes based on statistical significance, study quality, and size. RESULTS: From 113 systematic reviews, we found at least probable systematic review evidence of cardiovascular toxicity for 18 agents, including high- and all-grade hypertension for bevacizumab, ramucirumab, axitinib, cediranib, pazopanib, sorafenib, sunitinib, vandetanib, aflibercept, abiraterone, and enzalutamide, and all-grade hypertension for nintedanib; high- and all-grade arterial thromboembolism (includes cardiac and/or cerebral events) for bevacizumab and abiraterone, high-grade arterial thromboembolism for trastuzumab, and all-grade arterial thromboembolism for sorafenib and tamoxifen; high- and all-grade venous thromboembolism (VTE) for lenalidomide and thalidomide, high-grade VTE for cetuximab and panitumumab, and all-grade VTE for bevacizumab; high- and all-grade left ventricular ejection fraction decline or congestive heart failure for bevacizumab and trastuzumab, and all-grade left ventricular ejection fraction decline/congestive heart failure for pazopanib and sunitinib; and all-grade corrected QT interval prolongation for vandetanib. CONCLUSIONS: Our review provides an accessible summary of the cardiovascular toxicity of targeted therapy to assist clinicians and patients when managing cardiovascular health.

Diagnostic and health service pathways to diagnosis of cancer-registry notified cancer of unknown primary site (CUP).

BACKGROUND: Cancer of unknown primary (CUP) is a late-stage malignancy with poor prognosis, but we know little about what diagnostic tests and procedures people with CUP receive prior to diagnosis. The purpose of this study was to determine how health service utilisation prior to diagnosis for people with cancer-registry notified CUP differs from those notified with metastatic cancer of known primary. METHODS: We identified people with a cancer registry notification of CUP (n = 327) from the 45 and Up Study, a prospective cohort of 266,724 people ≥45 years in New South Wales, Australia, matched with up to three controls with a diagnosis of metastatic cancer of known primary (n = 977). Baseline questionnaire data were linked to population health data to identify all health service use, diagnostic tests, and procedures in the month of diagnosis and 3 months prior. We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After adjusting for age and educational attainment, people with a cancer-registry notified CUP diagnosis were more likely to be an aged care resident (OR = 2.78, 95%CI 1.37-5.63), have an emergency department visit (OR = 1.65, 95%CI 1.23-2.21), serum tumor marker tests (OR = 1.51, 95%CI 1.12-2.04), or a cytology test without immunohistochemistry (OR = 2.01, 95%CI 1.47-2.76), and less likely to have a histopathology test without immunohistochemistry (OR = 0.43, 95%CI 0.31-0.59). Neither general practitioner, specialist, allied health practitioner or nurse consultations, hospitalisations, nor imaging procedures were associated with a CUP diagnosis. CONCLUSIONS: The health service and diagnostic pathway to diagnosis differs markedly for people notified with CUP compared to those with metastatic cancer of known primary. While these differences may indicate missed opportunities for earlier detection and appropriate management, for some patients they may be clinically appropriate.