Association of obesity with prostate cancer: a case-control study within the population-based PSA testing phase of the ProtecT study.

BACKGROUND: Obesity has been inconsistently linked to prostate cancer, mainly with mortality rather than incidence. Few large-scale studies exist assessing obesity in relation to prostate-specific antigen (PSA)-detected prostate cancer. METHODS: We used cases and stratum-matched controls from the population-based PSA-testing phase of the Prostate testing for cancer and Treatment study to examine the hypothesis that obesity as measured by body mass index (BMI), waist circumference and waist-to-hip ratio (WHR) is associated with increased prostate cancer risk, and with higher tumour stage and grade. In all, 2167 eligible cases and 11 638 randomly selected eligible controls with PSA values were recruited between 2001 and 2008. A maximum of 960 cases and 4156 controls had measurement data, and also complete data on age and family history, and were included in the final analysis. BMI was categorised as <25.0, 25.0-29.9, ≥ 30.0 in kg m(-2). RESULTS: Following adjustment for age and family history of prostate cancer, we found little evidence that BMI was associated with total prostate cancer (odds ratio (OR): 0.83, 95% confidence interval (CI): 0.67, 1.03; highest vs lowest tertile; P-trend 0.1). A weak inverse association was evident for low-grade (OR: 0.76, 95% CI: 0.59, 0.97; highest vs lowest tertile; P-trend 0.045) prostate cancer. We found no association of either waist circumference (OR: 0.94, 95% CI: 0.80, 1.12; highest vs lowest tertile) or waist-to-hip ratio (WHR; OR: 0.93, 95% CI: 0.77, 1.11; highest vs lowest tertile) with total prostate cancer, and in analyses stratified by disease stage (all P-trend>0.35) or grade (all P-trend>0.16). CONCLUSION: General adiposity, as measured by BMI, was associated with a decreased risk of low-grade PSA-detected prostate cancer. However, effects were small and the confidence intervals had limits very close to one. Abdominal obesity (as measured by WHR/waist circumference) was not associated with PSA-detected prostate cancer.

Diagnostic radiation procedures and risk of prostate cancer.

Exposure to ionising radiation is an established risk factor for many cancers. We conducted a case-control study to investigate whether exposure to low dose ionisation radiation from diagnostic x-ray procedures could be established as a risk factor for prostate cancer. In all 431 young-onset prostate cancer cases and 409 controls frequency matched by age were included. Exposures to barium meal, barium enema, hip x-rays, leg x-rays and intravenous pyelogram (IVP) were considered. Exposures to barium enema (adjusted odds ratio (OR) 2.06, 95% confidence interval (CI) 1.01-4.20) and hip x-rays (adjusted OR 2.23, 95% CI 1.42-3.49) at least 5 years before diagnosis were significantly associated with increased prostate cancer. For those with a family history of cancer, exposures to hip x-rays dating 10 or 20 years before diagnosis were associated with a significantly increased risk of prostate cancer: adjusted OR 5.01, 95% CI 1.64-15.31 and adjusted OR 14.23, 95% CI 1.83-110.74, respectively. Our findings show that exposure of the prostate gland to diagnostic radiological procedures may be associated with increased cancer risk. This effect seems to be modified by a positive family history of cancer suggesting that genetic factors may play a role in this risk association.

Dietary zinc intake and brain cancer in adults: a case-control study.

Little is known about the aetiology of brain tumours. One putative factor suggested from animal models is a protective effect of dietary Zn. We tested the hypothesis that increased compared with low dietary Zn intake is protective against brain tumour development. We conducted a population-based case-control study in the UK, of adults aged 18-69 years, between 2001 and 2004 aiming to identify possible risk factors. Dietary information was collected from 637 cases diagnosed with a glioma or meningioma, and 876 controls. Data were obtained from a self-completed FFQ. Multivariate logistic regression analysis was conducted, adjusting for socio-demographic factors, season of questionnaire return, multivitamin supplementation and energy intake. Although a weak protective effect was observed for the third quartile of intake (normal compared with low intake) in the meningioma group, this was limited to the specific brain tumour subtype and quartile, and was not significant after also adjusting for intake of other elements. Overall there was no significant effect of Zn intake. No association or dose-response relationship was observed between increased compared with low Zn intake and risk of glioma or meningioma.

Genetic analysis of the interleukin-1 receptor antagonist and its homologue IL-1L1 in alopecia areata: strong severity association and possible gene interaction.

Alopecia areata is an inflammatory hair loss disease with a major genetic component. The presence of focal inflammatory lesions with perifollicular T-cell infiltrates reflects the importance of local cytokine production in the pathogenesis. In addition to its fundamental pro-inflammatory role, the interleukin-1 (IL-1) system has major effects on hair growth regulation in vitro, with the inhibitory actions of IL-1alpha and IL-1beta being opposed by the receptor antagonist IL-1ra. The novel interleukin-1 like molecule 1 (IL-1L1) which has greatest gene sequence homology with IL1RN, the gene encoding IL-1ra, is another potential IL-1 antagonist. In view of previous studies suggesting a significant role for IL1RN polymorphisms in the pathogenesis of autoimmune/inflammatory disease, we have analysed polymorphisms of IL-1ra (IL1RN+2018) and its homologue IL-1L1 (IL1L1+4734) in a case-control association study on 165 patients and a large number of matched controls. Homozygosity for the rare allele of IL1RN (IL1RN*2) was significantly associated with alopecia areata [odds ratio (OR) = 1.89, 95% CI (1.09, 3.28); P = 0.02], confirming our previous findings of significant association with the IL1RN variable number tandem repeat (VNTR). The results also revealed a novel association involving a polymorphism of the interleukin-1 receptor antagonist homologue IL1L1 at position + 4734, IL1RN+2018, and alopecia areata. The effect of a genotype combining three copies of the rare alleles at the IL1RN and IL1L1 loci conferred a more than additive increase in the risk of disease compared to IL1RN+2018 or IL1L1+4734 alone [OR 3.37 (1.60, 7.06); P = 0.002], suggesting possible synergy between the IL1RN and IL1L1 genes. This effect was stronger in patients with severe disease (alopecia totalis/universalis) [OR 4.62 (1.87, 11.40), P = 0.0022], and in those with early age at onset (< 20 years) [OR = 6.38 (2.64, 15.42), P = 0.0002]. Our results suggest that these polymorphisms within IL1RN and IL1L1 themselves or a gene in linkage disequilibrium with IL1RN and IL1L1 predispose to the more severe forms of alopecia areata.