Interrelationships between plasma testosterone, SHBG, IGF-I, insulin and leptin in prostate cancer cases and controls.

Despite strong indirect evidence that androgens stimulate prostate cancer development, data from most analytical studies on this association have been negative. To further investigate this issue, we studied the interrelationships between androgenicity and insulin-like growth factor I (IGF-I), insulin and leptin. Within a prospective cohort study, we measured testosterone, sex hormone-binding globulin (SHBG) and IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, insulin and leptin, in plasma from 149 cases and 298 controls. Testosterone correlated positively with SHBG, whereas testosterone and SHBG correlated inversely with IGF-I, IGFBP-3, insulin, leptin and body mass index (BMI). Indices of free testosterone showed an inverse linear correlation with leptin (P<0.01), and a strong drop in the 5th quintile of BMI. However, levels of free testosterone showed non-linear relationships over quintiles of insulin and IGF-I, with a significant increase in the second quintile of IGF-I compared with other levels. The absence of an association between plasma levels of androgens and prostate cancer risk in analytical studies, despite the strong indirect evidence of their tumour-stimulating effects, may reflect the complex and mostly inverse associations of androgenicity to IGF-I, insulin and leptin which are hormones that have also been implicated as risk factors for prostate cancer.     

Cadmium in blood and urine--impact of sex,age, dietary intake,iron status,and former smoking--association of renal effects

We studied determinants of cadmium status and kidney function in nonsmoking men and women living on farms in southern Sweden. Median blood Cd (BCd) was 1.8 nmol/L (range, 0.38-18) and median urinary Cd (UCd) was 0.23 nmol/mmol creatinine (range, 0.065-0.99). The intake of Cd per kilogram body weight did not significantly differ between sexes and did not correlate with BCd or UCd, which may be explained by a low and varying bioavailibility of Cd from food items. However, when a subgroup of the study population, couples of never-smoking men and women, were compared, a lower intake per kilogram body weight was found in the women, but the women had a 1.8 times higher BCd and a 1.4 times higher UCd. The higher female BCd and UCd may be explained by higher absorption due to low iron status. BCd and UCd both increased with age and were higher in the ex-smokers, who had stopped smoking more than 5 years before the study, compared to never-smokers. The contribution of locally produced food to the total Cd intake was relatively low and varied. Males living in areas with low soil Cd had lower UCd than the others. However, Cd levels in kidneys from pigs, fed locally produced cereals, did not predict BCd or UCd in humans at the same farms. The kidney function parameter ss2-microglobulin-creatinine clearance was related to UCd, whereas urinary protein-HC, N-acetyl-ss-glucoseaminidase or albumin-creatinine clearance was not when age was accounted for. Hence, even at the low exposure levels in this study population, there was an indication of effect on biochemical markers of renal function.     

Demographic factors associated with hantavirus infection in bank voles (Clethrionomys glareolus)

The bank vole (Clethrionomys glareolus) is the natural reservoir of Puumala virus (PUUV), a species in the genus Hantavirus. PUUV is the etiologic agent of nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome. Factors that influence hantavirus transmission within host populations are not well understood. We evaluated a number of factors influencing on the association of increased PUUV infection in bank voles captured in a region in northern Sweden endemic for the virus. Logistic regression showed four factors that together correctly predicted 80% of the model outcome: age, body mass index, population phase during sampling (increase, peak, or decline/low), and gender. This analysis highlights the importance of population demography in the successful circulation of hantavirus. The chance of infection was greatest during the peak of the population cycle, implying that the likelihood of exposure to hantavirus increases with increasing population density.     

Expression of prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) in ileum and other extraprostatic tissues

Prostate-specific antigen (PSA) is a widely used marker for prostate cancer. In the literature, there are reports of nonprostatic expression of PSA that potentially can affect early diagnosis. However, the results are scattered and inconclusive, which motivated us to conduct a more comprehensive study of the tissue distribution of PSA and the closely related protein human glandular kallikrein 2 (hK2). RT-PCR, in situ hybridization and immunohistochemistry were used to detect expression of both PSA and hK2 in secretory epithelial cells of trachea, thyroid gland, mammary gland, salivary gland, jejunum, ileum, epididymis, seminal vesicle and urethra, as well as in Leydig cells, pancreatic exocrine glands and epidermis. Immunometric measurements revealed that the concentration of PSA in nonprostatic tissues represents less than 1% of the amount in normal prostate. Pronounced expression of PSA was detected in the Paneth cells in ileum, which prompted us to compare functional parameters of PSA in ileum and prostate. We found that in homogenates from these 2 tissues, PSA manifested equivalent amidolytic activity and capacity to form complexes with protease inhibitors in blood in vitro. Thus, PSA released from sources other than the prostate may add to the plasma pool of this protein, but given the lower levels detected from those sites, it is unlikely that nonprostatic PSA normally can interfere with the diagnosis of prostate cancer. Nevertheless, this risk should not be neglected as it may be of clinical significance under certain circumstances. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html.     

Prognostic factors in invasive cutaneous malignant melanoma: a population-based study and review

A population-based study from Sweden identified 711 patients with cutaneous malignant melanoma diagnosed in 1965, 1975, 1985 and 1989. Prognostic factors were evaluated and a review of the literature was performed. On univariate analysis, thick tumours (> 0.8 mm) (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.6-2.1), increasing Clark level (OR 1.8, 95% CI 1.6-2.0), ulceration (OR 1.8, 95% CI 1.6-2.0), nodular melanoma (OR 1.5, 95% CI 1.3-1.6) and increasing age (continuous variable, P < 0.0001) were associated with a shorter survival. Location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-0.9) were associated with improved survival. On multivariate analysis, thick tumours (> 0.8 mm) (OR 1.5, 95% CI 1.2-1.7) and ulceration (OR 1.4, 95% CI 1.2-1.6) were independently related to a poor prognosis, while location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-1.0) were associated with improved survival. No difference in mean tumour thickness was seen over time, but there was a significant increase in the percentage of thin melanomas (< 0.8 mm) in 1985 (P = 0.01) and 1989 (P = 0.002) compared with 1965. The incidence of melanomas with inflammation increased significantly (P = 0.04), as did age at diagnosis (P = 0.005).     

Prolactin levels,breast-feeding and milk production in a cohort of young healthy women from high-risk breast cancer families: implications for breast cancer risk

High prolactin levels have been associated with increased breast cancer risk. Prolactin is essential for breast-feeding. Prolactin is lowered primarily by the first full-term pregnancy and not by subsequent pregnancies. The protection from breast cancer conferred by a long breast-feeding duration (>1 year) seems to be much greater for women with BRCA1 mutations (45%) than for women in the general population (4%). One study reported poor milk production to be more common in BRCA1 carriers (75%) than in non-carriers (36%). We aimed to explore the relationships between prolactin levels, breast-feeding duration, milk production and BRCA carrier status in young healthy women from high-risk breast cancer families. Questionnaires including information on reproductive factors and lifestyle were completed by 269 healthy women, aged 40 years or younger. Body measurements and plasma prolactin levels were obtained during cycle days 5-10 and 18-23. Prolactin was higher in nulliparous than in parous women (P < 0.0001). In parous women, post-lactational prolactin levels in both cycle phases were significantly negatively associated with breast-feeding duration of the first child (P /= 0.12). Prolactin was higher in women who reported insufficient versus sufficient milk production (P 相似文献   

Mapping of a novel ocular and cutaneous malignant melanoma susceptibility locus to chromosome 9q21.32

An estimated 10% of all cutaneous malignant melanoma (CMM) cases are inherited, but the genetics of familial CMM are largely unknown. Ocular malignant melanoma (OMM), which is rare, may be associated with familial CMM. We performed a genome-wide scan of two Danish pedigrees with multiple cases of OMM (N = 10) and CMM (N = 3) and other malignancies (with no germline mutations in CDKN2A, CDK4, BRCA1, and BRCA2) to identify melanoma susceptibility genes. Results of parametric linkage analysis are presented as logarithm of the odds (LOD) scores, and all P values are two-sided. Peak two-point parametric LOD score of 2.2 (P = .0007) at D9S167 on chromosome 9q21 was observed. Targeted analysis of a third Danish family with OMM and CMM patients confirmed 9q21 linkage, providing a combined four-point parametric LOD score of 3.02 (nominal P = .00003 and genome-wide P = .086). Two families shared a common haplotype comprising three adjacent and highly polymorphic markers, limiting the region to less than 5 cM and 3 Mbp at 9q21.32. Expression of RASEF, a known gene in this region, was examined in tumor tissue from 10 sporadic CMM lesions and was found to be decreased in 70% of these tumors compared with RASEF expression in a human reference RNA pool from 10 different cell types and in 10 breast tumors.     

Comparison of abdominal adiposity and overall obesity in relation to risk of small intestinal cancer in a European Prospective Cohort

Background

The etiology of small intestinal cancer (SIC) is largely unknown, and there are very few epidemiological studies published to date. No studies have investigated abdominal adiposity in relation to SIC.

Methods

We investigated overall obesity and abdominal adiposity in relation to SIC in the European Prospective Investigation into Cancer and Nutrition (EPIC), a large prospective cohort of approximately half a million men and women from ten European countries. Overall obesity and abdominal obesity were assessed by body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Multivariate Cox proportional hazards regression modeling was performed to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs). Stratified analyses were conducted by sex, BMI, and smoking status.

Results

During an average of 13.9 years of follow-up, 131 incident cases of SIC (including 41 adenocarcinomas, 44 malignant carcinoid tumors, 15 sarcomas and 10 lymphomas, and 21 unknown histology) were identified. WC was positively associated with SIC in a crude model that also included BMI (HR per 5-cm increase = 1.20, 95 % CI 1.04, 1.39), but this association attenuated in the multivariable model (HR 1.18, 95 % CI 0.98, 1.42). However, the association between WC and SIC was strengthened when the analysis was restricted to adenocarcinoma of the small intestine (multivariable HR adjusted for BMI = 1.56, 95 % CI 1.11, 2.17). There were no other significant associations.

Conclusion

WC, rather than BMI, may be positively associated with adenocarcinomas but not carcinoid tumors of the small intestine.

Impact

Abdominal obesity is a potential risk factor for adenocarcinoma in the small intestine.

     

Contextual determinants of alcohol consumption changes and preventive alcohol policies: a 12-country European study in progress

Beginning with France in the 1950s, alcohol consumption has decreased in Southern European countries with few or no preventive alcohol policy measures being implemented, while alcohol consumption has been increasing in Northern European countries where historically more restrictive alcohol control policies were in place, even though more recently they were loosened. At the same time, Central and Eastern Europe have shown an intermediate behavior. We propose that country-specific changes in alcohol consumption between 1960 and 2008 are explained by a combination of a number of factors: (1) preventive alcohol policies and (2) social, cultural, economic, and demographic determinants. This article describes the methodology of a research study designed to understand the complex interactions that have occurred throughout Europe over the past five decades. These include changes in alcohol consumption, drinking patterns and alcohol-related harm, and the actual determinants of such changes.