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.     

Combined effects of maternal smoking status and dietary intake related to weight gain and birth size parameters

OBJECTIVE: To investigate the interaction of smoking status and dietary intake during pregnancy and its relationship to maternal weight gain and birth size parameters. DESIGN: An observational prospective study. SETTING: Free-living conditions. POPULATION: Four hundred and eight healthy pregnant Icelandic women. METHODS: Maternal smoking status, lifestyle factors and dietary habits were evaluated with questionnaires. Intake of foods and supplements was also estimated with a semiquantitative food frequency questionnaire for the previous 3 months. All questionnaires were filled out between 11 and 15 weeks and between 34 and 37 weeks of gestation. Smoking status in relation to optimal and/or excessive weight gain during pregnancy was represented with logistic regression controlling for potential confounding factors. MAIN OUTCOME MEASURES: Maternal weight gain, smoking status, dietary intake and birthweight. RESULTS: Women who smoked throughout pregnancy were unlikely to gain optimal weight or more (OR 0.51, 95% CI 0.27-0.97), whereas smoking cessation in connection with pregnancy ('former smokers') doubled the risk of excessive weight gain (OR 2.03, 95% CI 1.24-3.35). The latter association was no longer significant after adjustment for dietary factors and other confounding factors. Former smokers ate the least amount of fruit and vegetables (fruit: 129 versus 180 and 144 g/day (median), P= 0.038; vegetables: 53 versus 76 and 72 g/day, P= 0.026 for former smokers, nonsmokers and smokers, respectively). Birthweight was lowest among infants born to smokers, but birthweight was similar for former smokers and nonsmokers (3583 +/- 491 g versus 3791 +/- 461 g and 3826 +/- 466 g, respectively; P= 0.003). CONCLUSIONS: Smoking cessation in early pregnancy or pre-pregnancy is not associated with low birthweight. It is, however, associated with excessive maternal weight gain and a low fruit and vegetable intake.     

The Association between Parathyroid Hormone, Vitamin D and Bone Mineral Density in 70-Year-Old Icelandic Women

Parathyroid hormone (PTH) may be an important determinant of cortical bone remodeling in the elderly. Vitamin D status is one of the determining factors in this relationship. The aim of this study was to quantify the relationship between serum PTH, vitamin D and bone mineral density (BMD) in elderly women in Reykjavik (64° N), where daily intake of cod liver oil is common and mean calcium intake is high. ln PTH correlated inversely with 25(OH)D (r=−0.26, p<0.01). In multivariate analysis PTH correlated inversely with whole body BMD (mostly cortical bone) (R ²= 2.2%, p = 0.04) but not with the lumbar spine BMD, reflecting more cancellous bone. No association was found between 25(OH)D levels and BMD at any site in univariate or multivariate analysis. Osteocalcin, a measure of bone turnover, was negatively associated with BMD and this association remained significant when corrected for PTH levels. In summary, in this fairly vitamin D replete population with high calcium intake, PTH was negatively associated with total body BMD. We infer that suppression of PTH may reduce cortical bone loss, but other factors are likely to contribute to age-related bone remodeling and osteoporosis. Received: 3 January 2000 / Accepted: 10 April 2000     

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.     

Pregnant women’s preference for cesarean section and subsequent mode of birth – a six-country cohort study

Introduction: The rate of cesarean section (CS) for non-medical reasons has risen and it is a concern for health care. Women’s preferences may vary across countries for psychosocial or obstetric reasons.

Methods: A prospective cohort study of 6549 women in routine antenatal care giving birth in Belgium, Iceland, Denmark, Estonia, Norway or Sweden. Preference for mode of birth was self-reported in mid-pregnancy. Birth outcome data were collected from hospital records.

Results: A CS was preferred by 3.5% of primiparous women and 8.7% of the multiparous women. Preference for CS was associated with severe fear of childbirth (FOC), with a negative birth experience in multiparous women and with depressive symptoms in the primiparous. Women were somewhat more prone to prefer a cesarean in Iceland, odd ratio (OR) 1.70 (1.02–2.83), adjusted for age, education, depression, FOC, history of abuse, previous cesarean and negative birth experience. Out of the 404 women who preferred CS during pregnancy, 286 (70.8%) delivered by CS, mostly for a medical indication. A total of 9% of the cesareans in the cohort had a non-medical indication only.

Conclusions: Women’s preference for CS often seems to be due to health concerns. Both medical and psychological factors need to be addressed in antenatal counseling. Obstetricians need to convey accurately to women the risks and benefits of CS in her specific case. Maternity professionals should identify and explore psychosocial reasons for women’s preferences.     

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.