Cancer incidence among Finnish seafarers, 1967–92

A cohort of 30,940 male and 11,529 female seafarers registered in the files of Seafarers' Pension Fund in Finland was followed up through the Finnish Cancer Registry for cancer in 1967–92. Among male seafarers, there were 1,199 cases of cancer, which corresponds to the average cancer incidence in Finnish men. There was a statistically significant excess of non-melanoma skin cancer (standardized incidence ratio [SIR]=1.8, 95 percent confidence interval [CI]=1.2–2.5) and mesothelioma (SIR=2.9, CI=1.2–5.6) in the follow-up category of 20 or more years since the first employment. Alcohol-related cancers were increased among seafarers (SIR for cancer of the mouth and pharynx = 1.; esophagus = 1.4; and liver = 1.5; combined CI=1.1–1.9). Deck crews had a significantly high risk of cancer of the pancreas (SIR=2.0) and also prostate after 10 years since first employment (SIR=1.6). Occupational asbestos exposure among seafarers is likely strong enough to cause excess cases of mesothelioma but not of lung cancer. Occupational exposures also may be associated with increased risk of cancers of the kidney, pancreas, prostate and old-age brain cancer in some of the main occupational categories. Cumulative ultraviolet radiation likely doubles the risk of nonmelanoma skin cancer among older men and repeated sunburns that of skin melanoma in ages below 30 (SIR among deck and engine crew = 4.6, CI=3.1–6.5). Female ship personnel had a significantly elevated total cancer risk (observed number of cases = 732) which increased over follow-up time (SIR in the category 20 years since the first employment was 1.3, CI=1.1–1.5). This excess was attributable primarily to lung cancer (SIR=2.6, CI=2.0–3.3). Also cancers of the cervix uteri, vulva, and vagina showed significant excess after 10 to 20 years since first employment aboard.Address correspondence to Dr Pukkala, Finnish Cancer Registry, Litsankatu 21 B, FIN-00170 Helsinki, Finland. The Finnish Work Environment Fund financially supported this project.Dr Pukkala is with the Finnish Cancer Registry, Helsinki, Finland. Dr Saarni is with the Regional Institute of Occupational Health, Turku, Finland.     

Insulin-like growth factor-I and C-reactive protein during pregnancy and maternal risk of non-epithelial ovarian cancer: a nested case�Ccontrol study

Background

Insulin-like growth factor-I (IGF-I) and C-reactive protein (CRP) may be positively associated with the risk of epithelial ovarian cancer (EOC) but no previous studies have investigated their associations with non-epithelial ovarian cancers (NEOC).

Methods

A case?Ccontrol study was nested within the Finnish Maternity Cohort. Case subjects were 58 women diagnosed with sex cord-stromal tumors (SCST) and 30 with germ cell tumors (GCT) after recruitment. Control subjects (144 for SCST and 74 for GCT) were matched for age, parity, and date of blood donation of the index case.

Results

Doubling of IGF-I concentration was not related to maternal risk of either SCST (OR 0.97, 95% CI 0.58?C1.62) or GCT (OR 1.13, 95% CI 0.51?C2.51). Similarly, doubling of CRP concentrations was not related to maternal risk of either SCST (OR 1.10, 95% CI 0.85?C1.43) or GCT (OR 0.93, 95% CI 0.68?C1.28).

Conclusions

Pre-diagnostic IGF-I and CRP concentrations during the first trimester of pregnancy were not associated with increased risk of NEOC in the mother. Risk factors for NEOC may differ from those of EOC.     

Pinpointing the neural signatures of single-exposure visual recognition memory

Memories of the images that we have seen are thought to be reflected in the reduction of neural responses in high-level visual areas such as inferotemporal (IT) cortex, a phenomenon known as repetition suppression (RS). We challenged this hypothesis with a task that required rhesus monkeys to report whether images were novel or repeated while ignoring variations in contrast, a stimulus attribute that is also known to modulate the overall IT response. The monkeys’ behavior was largely contrast invariant, contrary to the predictions of an RS-inspired decoder, which could not distinguish responses to images that are repeated from those that are of lower contrast. However, the monkeys’ behavioral patterns were well predicted by a linearly decodable variant in which the total spike count was corrected for contrast modulation. These results suggest that the IT neural activity pattern that best aligns with single-exposure visual recognition memory behavior is not RS but rather sensory referenced suppression: reductions in IT population response magnitude, corrected for sensory modulation.

Under the right conditions, we are very good at remembering the images that we have seen: we can remember thousands of images after viewing each only once and only for a few seconds (1, 2). How our brains support this remarkable ability, often called “visual recognition memory” (3), is not well understood. The most prominent proposal to date suggests that memories about whether images have been encountered before are signaled in high-level visual brain areas such as inferotemporal cortex (IT) and perirhinal cortex via adaptation-like reductions of the population response to repeated as compared to novel stimuli, a phenomenon referred to as repetition suppression (RS) (4–9). Repetition suppression exhibits the primary attributes needed to account for the vast capacity of single-exposure visual memory behavior: response decrements in subsequent exposures are selective for image identity (even after viewing an extensive sequence of other images), and last for several minutes to hours (5, 6, 10). RS has also been shown to account for behavior in an image recognition memory task: a linear decoder with positive weights can predict single-exposure visual recognition memory behavior from neural responses in IT cortex (10).Despite the fact that the RS hypothesis is consistent with available evidence, it seems likely to be too simplistic an explanation for visual recognition memory encoding. In particular, it is well known that sensory neurons such as those of IT cortex are modulated not only by image memory, but also by stimulus properties such as image contrast (11). It is thus unclear whether and how these stimulus-induced effects interfere with judgments of whether images are novel or have been encountered before, and if they do not, how image memory can be decoded from neural responses in a way that disambiguates it from changes in these stimulus properties. To investigate this, we measured behavioral and neural responses of monkeys trained to report whether images were novel or repeated while disregarding image contrast (Fig. 1A).Open in a separate windowFig. 1.Visual memory behavior. (A) The contrast-invariant, single-exposure visual memory task. The monkeys viewed a sequence of images and reported whether they were novel (never seen before) or repeated (seen exactly once) while ignoring randomized changes in contrast. Monkeys were trained to saccade to one of two response targets to indicate their choice (red arrows). Images were repeated with a randomly chosen delay between the first and repeated presentation (“n-back”). (B) Images were displayed at one of two contrast levels, yielding two conditions for novel images, high (H) and low (L), and four conditions for repeated images: HH (repeated H preceded by novel H), LL (repeated L preceded by novel L), HL (repeated L preceded by novel H), and LH (repeated H preceded by novel L). The four repeated conditions were organized into same-contrast and mixed-contrast groups depending on whether the initial and repeated presentations were at the same or different contrasts, respectively. (C) Behavioral performance for the data pooled across monkeys in the task, where small black dots indicate average performance for an individual session and large colored dots indicate the average performance across sessions. A measure of contrast invariance, I, was computed as the ratio of the variance across contrast conditions and the variance with respect to the maximally contrast-modulated pattern after taking overall performance into account, subtracted from 1 (SI Appendix, SI Methods). Insets illustrate the expected behavioral pattern with minimal (I = 0) and maximal (I = 1) contrast invariance.     

Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease.

BACKGROUND--Dermatitis herpetiformis is a lifelong, gluten sensitive skin disease. Patients with dermatitis herpetiformis, similar to patients with coeliac disease not adhering to a gluten free diet, seem to have increased risk for lymphoma. AIMS--This study looked at the occurrence of malignancy and survival of patients with dermatitis herpetiformis and compared the results with those seen in patients with coeliac disease or in the general population. PATIENTS--A total of 305 adult patients with dermatitis herpetiformis diagnosed at the University Hospital of Tampere in 1970-1992 were studied. Most patients started a gluten free diet and at the end of the study 93% of the patients were adhering to the diet. A control group comprised 383 adult patients with coeliac disease, 81% of them adhered to a gluten free diet, 6% had a normal diet, and in 13% the diet history remained unknown. METHODS--The occurrence of malignant diseases and survival of the patients were assessed up to the end of 1993. Standardised incidence ratios (SIR) with 95% confidence intervals were used for the malignant diseases. The survival of the patients was compared with that of the general population. RESULTS--Thirteen (4.3%) patients with dermatitis herpetiformis developed 14 malignant disorders during the follow up (SIR 1.25; 95% confidence intervals 0.68 to 2.09). A non-Hodgkin's lymphoma occurred in four patients with dermatitis herpetiformis, significantly more than expected (SIR 10.3; 2.8-26.3). Thirteen (4.3%) patients with dermatitis herpetiformis died during the follow up but there was no increased general mortality. In coeliac disease, 13 (3.4%) patients developed malignancy (SIR 1.16; 0.62 to 1.97), 31 (8.1%) patients died but the survival rate did not differ from that in the general population. CONCLUSIONS--The incidence of non-Hodgkin's lymphoma was significantly increased in patients with dermatitis herpetiformis. The results also confirm that the patients with dermatitis herpetiformis treated mainly with a gluten free diet have no increased general mortality.     

Effects of dietary sodium on reactive oxygen species formation and endothelial dysfunction in low-density lipoprotein receptor-deficient mice on high-fat diet

Hypertension and high serum cholesterol level are important risk factors for atherosclerosis and coronary heart disease. In the present study we tested the hypothesis whether high sodium intake, when given in combination with Western type high-fat diet, induces endothelial dysfunction and promotes atherosclerosis. Furthermore, the role and enzyme sources of increased oxidative stress were examined. Low-density lipoprotein receptor-deficient mice (LDLR^−/−) and control C57Bl/6 mice received either high-fat, normal-sodium diet (fat 18% and cholesterol 0.5%; NaCl 0.7%; w/w) or high-fat, high-sodium diet (7% NaCl w/w) for 12 weeks. Superoxide formation was assessed by lucigenin enhanced chemiluminescence, endothelial functions were examined ex vivo, and atherosclerotic lesions from the aorta were assessed by light microscopy. High-fat, high-sodium diet increased systolic blood pressure in LDLR^−/− mice but not in C57Bl/6 mice, whereas it induced cardiac hypertrophy in both mouse strains. Dietary combination of fat and sodium induced endothelial dysfunction in LDLR^−/− mice. Preincubation with a superoxide scavenger Tiron normalized endothelial dysfunction, whereas the hydrogen peroxide scavenger catalase did not alter endothelial function. High sodium intake induced superoxide formation in LDLR^−/− mice on high-fat diet. Stimulation of muscarinic receptors in the endothelial cells by acetylcholine increased superoxide generation, whereas preincubation with the nitric oxide synthase (NOS) inhibitor L-arginine methyl ester or endothelium removal reduced superoxide production. Inhibition of nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase by apocynin decreased vascular superoxide formation whereas the xanthine oxidase inhibitor oxypurinol did not significantly affect oxidative stress in LDLR^−/− mice. In conclusion, the detrimental effects of dietary sodium on endothelial function and progression of atherosclerosis in LDLR^−/− mice on high-fat diet are mediated by increased ROS formation mainly through uncoupled NOS and NADPH oxidase. The present study also underscores the importance of superoxide and endothelial NOS uncoupling in the pathogenesis of endothelial dysfunction.     

Age‐time risk patterns of solid cancers in 60 901 non‐Hodgkin lymphoma survivors from Finland,Norway and Sweden

Survival after non‐Hodgkin lymphoma (NHL) has increased thanks to improved treatment but NHL survivors have an increased risk of second neoplasms. The assessment of cancer risk patterns after NHL may help to quantify the late side‐effects of therapy. Poisson regression was used to estimate relative risks (RRs) and absolute incidence rates for nine solid tumours based on a nationwide cohort of 60 901 NHL survivors from Finland, Norway and Sweden. Patients were diagnosed between 1980 and 2006 and developed 6815 s neoplasms. NHL patients showed an increased risk of each of the nine investigated cancer sites: prostate and pancreas (both RRs 1·28), breast (1·37), colorectum (1·48), urinary bladder (1·52), stomach and lung (both RRs 1·87), skin (melanoma 2·27) and kidney (2·56). The RRs showed a U‐shaped relationship with time after NHL for all nine‐second cancer types. NHL diagnosis early in life was a risk factor for the development of second cancers with the exception of melanoma, but a risk excess was even observed in patients diagnosed with NHL at age 80+ years. The present study provides accurate estimates on the adverse late effects of NHL therapy, which should guide the establishment of cancer prevention strategies in NHL survivors.