Estrogen–progestin use and breast cancer characteristics in lean and overweight postmenopausal women

Purpose

We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines.

Methods

We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS.

Results

On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18–8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47–18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS.

Conclusions

We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.

     

Occupational exposure to solvents and bladder cancer: A population‐based case control study in Nordic countries

The objective of the study was to assess the relationship between exposure to selected solvents and the risk of bladder cancer. This study is based on the Nordic Occupational Cancer (NOCCA) database and comprises 113,343 cases of bladder cancer diagnosed in Finland, Iceland, Norway and Sweden between 1961 and 2005 and 566,715 population controls matched according to country, sex and birth year. Census‐based occupational titles of the cases and controls were linked with the job exposure matrix created by the NOCCA project to estimate quantitative cumulative occupational exposures. A conditional logistic regression model was used to estimate hazard ratios (HRs) and their 95% confidence intervals (95% CI). Increased risks were observed for trichloroethylene (HR 1.23, 95% CI 1.12–1.40), toluene (HR 1.20, 95% CI 1.00–1.38), benzene (HR 1.16, 95% CI 1.04–1.31), aromatic hydrocarbon solvents (HR 1.10, 95% CI 0.94–1.30) and aliphatic and alicyclic hydrocarbon solvents (HR 1.08, 95% CI 1.00–1.23) at high exposure level versus no exposure. The highest excess for perchloroethylene was observed at medium exposure level (HR 1.12, 95% CI 1.02–1.23). The study provides evidence of an association of occupational exposure to trichloroethylene, perchloroethylene, aromatic hydrocarbon solvents, benzene and toluene and the risk of bladder cancer.     

Occupational exposure to wood dust and risk of nasal and nasopharyngeal cancer: A case‐control study among men in four nordic countries—With an emphasis on nasal adenocarcinoma

The current study aims to provide stronger evidence to aid in our understanding of the role of cumulative occupational exposure to (softwood‐dominated) mixed wood dust in aetiology of nasal cancer. We included broad exposure occurred in a range of wood‐processing occupation across varied industries in four Nordic countries. A population‐based case‐control study was conducted on all male cases with nasal adenocarcinoma (393 cases), other types of nasal cancer (2,446) and nasopharyngeal cancer (1,747) diagnosed in Finland, Sweden, Norway and Iceland between 1961 and 2005. For each case, five male controls, who were alive at the time of diagnosis of the case (index date), were randomly selected, matched by birth‐year and country. Cumulative exposures (CE)s to wood dust and formaldehyde before the index date were quantified based on a job‐exposure matrix linked to occupational titles derived from population censuses. Hazard ratios (HRs) for the CE of wood dust were estimated by conditional logistic regression, adjusted for CE to formaldehyde and 95% confidence intervals (CIs) were calculated. There was an increasing risk of nasal adenocarcinoma related to wood dust exposure. The HR in the highest CE category of wood dust (≥ 28.82 mg/m³‐years) was 16.5 (95% CI 5.05–54.1). Neither nonadenocarcinoma of the nose nor nasopharyngeal cancer could be linked to wood dust exposure. CE to softwood‐dominated mixed wood dusts is strongly linked with elevated risk in nasal adenocarcinoma but not with other types of nasal or nasopharyngeal cancer.     

Midlife metabolic factors and prostate cancer risk in later life

Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n = 9,097, enrolled 1967–1987) were followed for incident (n = 1,084 total; n = 378 advanced; n = 148 high‐grade) and fatal (n = 340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0–4) combining the risk factors: BMI ≥30 kg/m²; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mm Hg or taking antihypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dl or self‐reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high‐grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides were associated with prostate cancer risk. Higher metabolic syndrome score (3–4 vs 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p trend = 0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer.     

The effect of job loss on body weight during an economic collapse

Studies on the relationship between unemployment and body weight show a positive relationship between Body Mass Index (BMI) and unemployment at the individual level, while aggregate unemployment is negatively related to a population’s average BMI. The aim of this study was to examine the relationship between job loss and changes in body weight following the Icelandic economic collapse of 2008. The analysis relies on a health and lifestyle survey “Heilsa og líðan”, carried out by The Public Health Institute of Iceland in the years 2007 and 2009. The sample is a stratified random sample of 9,807 Icelanders between the ages of 18 and 79, with a net response rate of 42.1 % for individuals responding in both waves. A linear regression model was used when estimating the relationship between job loss following the economic collapse and changes in body weight. Family income and mental health were explored as mediators. Point estimates indicated that both men and women gain less weight in the event of a job loss relative to those who retained their employment. The coefficients of job loss were only statistically significant for females, but not in the male population. The results from all three models were inconsistent with results from other studies where job loss has been found to increase body weight. However, body weight has been shown to be procyclical, and the fact that the data used were gathered during a severe economic downturn might separate these results from earlier findings.     

Positive Association Between DNA Strand Breaks in Peripheral Blood Mononuclear Cells and Polyunsaturated Fatty Acids in Red Blood Cells From Women

Lipid peroxidation of polyunsaturated fatty acids (PUFA) generates reactive products that may cause DNA damage. To examine the possible relationship between DNA damage in peripheral blood mononuclear cells (PBMC) and the concentration of PUFA in red blood cells (RBC), endogenous DNA strand breaks, formamidopyrimidine DNA glycosylase (FPG) sites, and hydrogen peroxide (H₂O₂) sensitive sites were evaluated by the comet assay in blood samples from 98 Icelandic women. Fatty acid composition of RBC was analyzed by gas chromatography. Endogenous DNA strand breaks in PBMC correlated positively with the concentration of total PUFA, total n-3 PUFA, docosahexaenoic acid, linoleic acid, oleic acid, and palmitic acid in RBC. However, there was no association between FPG sites or H₂O₂ sensitive sites in DNA in PBMC and the concentration of total PUFA or total saturated fatty acid in RBC. As there was no association between oxidative DNA damage or sensitivity of DNA to oxidative stress and the concentration of PUFA in RBC, the positive association between endogenous DNA strand breaks in PBMC and the concentration of total PUFA in RBC is probably not related to oxidative stress.     

Interpreting trends in prostate cancer incidence and mortality in the five Nordic countries

Trends in incidence and mortality rates of prostate cancer were analyzed using data from the national cancer registries of Denmark, Finland, Iceland, Norway, and Sweden. Joinpoint regression models were used to quantify temporal trends for the period from 1980 to 2004. Incidence rates were increasing and similar in the Nordic countries during the 1980s. Around 1990, a more rapid incidence increase began in all Nordic countries except Denmark, where an increase was seen 5 years later. In 2001, incidence rates in Denmark were half of those seen in the other Nordic countries, but mortality rates varied only marginally among countries. Mean annual declines in prostate cancer mortality of 1.9% (95% CI = 0.4% to 3.3%) and 1.8% (95% CI = 0.5% to 3.0%) were observed from 1996 to 2004 in Finland and Norway, respectively. During the same period, mortality rates leveled off in Iceland and Sweden but continued to increase in Denmark. The rapid increase in incidence during the early 1990s coincided with the introduction of the prostate-specific antigen (PSA) test and conveys little information about the occurrence of potentially lethal disease. Mortality rates, however, have recently stabilized or declined in countries where PSA testing and curative treatment have been commonly practiced since the late 1980s. Although other explanatory factors may be in operation, these trends are consistent with a moderate effect of increased curative treatment of early diagnosed prostate cancer and improved treatment of more advanced disease.     

Assessing disease risk in genome-wide association studies using family history

We show how to use reports of cancer in family members to discover additional genetic associations or confirm previous findings in genome-wide association (GWA) studies conducted in case-control, cohort, or cross-sectional studies. Our novel family history-based approach allows economical association studies for multiple cancers, without genotyping of relatives (as required in family studies), follow-up of participants (as required in cohort studies), or oversampling of specific cancer cases (as required in case-control studies). We empirically evaluate the performance of the proposed family history-based approach in studying associations with prostate and ovarian cancers, using data from GWA studies previously conducted within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The family history-based method may be particularly useful for investigating genetic susceptibility to rare diseases for which accruing cases may be very difficult, by using disease information from nongenotyped relatives of participants in multiple case-control and cohort studies designed primarily for other purposes.     

Mortality,Reoperation, and Hospital Stay Within 90 Days of Primary and Secondary Antireflux Surgery in a Population-Based Multinational Study

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