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BACKGROUND: Results to date for the association between use of statins and prostate cancer (PCa) death in observational studies are inconsistent. We investigated the application of causal inference methods, which aim to address observational data as if they were from a randomised clinical trial (RCT). MATERIAL AND METHODS: We examined the association between statins and PCa-death in 14,926 men in PCBaSe Sweden. We used inverse probability weighted (IPW) estimation of marginal structural models (MSM), as well incorporating truncated IPW in the presence of time-dependent confounders (TDC) (e.g., disease severity), affected by the exposure. RESULTS: The baseline adjusted odds ratio (OR) was 0.62 (95%CI: 0.51-0.75), which compared risk of PCa-death between men on statins and men not on statins. The calculated IPW for the MSM were highly variable, with the smallest weight at 0.0019 and the largest at 13,574, resulting in an OR of 0.89 (95%CI: 0.69-1.14). Truncating the weights improved variability, reducing the largest weight to 13.16. The truncated MSM OR was 0.86 (95%CI: 0.81-0.91). CONCLUSION: An association of statins and risk of PCa-death could not be reliably discerned, due to lack of data on essential confounders, namely serum cholesterol levels and disease severity. No observational studies on statin-use to date present information on serum cholesterol levels and disease severity in one setting, highlighting the need for careful interpretation of investigations into drugs in relation to diseases other than their intended purpose in observational settings.

BACKGROUND Despite mounting evidence linking both calcium and IGF1, there is a lack of studies investigating any association between circulating levels of IGF1 and serum calcium. METHODS Serum calcium, IGF1, and IGF-binding protein 3 (IGFBP3) were measured for 5368 participants in NHANES III. We calculated multivariable-adjusted geometric means of serum concentrations of IGF1, IGFBP3, and IGF1/IGFBP3 by categories of calcium (lowest 5% (<1.16 mmol/l), mid 90%, and top 5% (≥1.31 mmol/l)). We also performed stratified analyses by sex, age, ethnicity, BMI, serum levels of vitamin D, and bone mineral density (BMD). RESULTS Overall, we found that circulating calcium was positively associated with circulating levels of IGF1 and IGFBP3, but not their molar ratio (i.e., geometric mean of IGF1 by increasing calcium categories: 237.63, 246.51, and 264.22 ng/nl; Ptrend: 0.43; Pfirst vs third category: 0.01). In particular, these associations were observed in women, people aged <60, non-Hispanic whites, those with vitamin D levels above the mean, and those with low BMD. In contrast, there was an inverse association with the molar ratio for those with BMI ≥30 kg/m(2). CONCLUSION We found an overall positive association between circulating levels of IGF1 and IGFBP3 and serum calcium. However, stratification by potential effect-modifiers did not support all suggested hypotheses. Our findings provide more insight into the interplay between calcium and IGF1, which in the future can be investigated in larger observational studies allowing for additional stratifications based on a combination of the different effect-modifiers investigated here.

Background: It is estimated that 20% of all cancer cases are caused by obesity. Vitamin D is thought to be one of the mechanisms underlying this association. This review aims to summarise the evidence for the mediating effect of vitamin D on the link between obesity and cancer. Methods: Three literature searches using PubMed and Embase were conducted to assess whether vitamin D plays an important role in the pathway between obesity and cancer: (1) obesity and cancer; (2) obesity and vitamin D; and (3) vitamin D and cancer. A systematic review was performed for (1) and (3), whereas a meta-analysis including random effects analyses was performed for (2). Results: (1) 32 meta-analyses on obesity and cancer were identified; the majority reported a positive association between obesity and risk of cancer. (2) Our meta-analysis included 12 original studies showing a pooled relative risk of 1.52 (95% CI: 1.33-1.73) for risk of vitamin D deficiency (<50 nmol/L) in obese people (body mass index >30 kg/m(2)). (3) 21 meta-analyses on circulating vitamin D levels and cancer risk were identified with different results for different types of cancer. Conclusion: There is consistent evidence for a link between obesity and cancer as well as obesity and low vitamin D. However, it seems like the significance of the mediating role of vitamin D in the biological pathways linking obesity and cancer is low. There is a need for a study including all three components while dealing with bias related to dietary supplements and vitamin D receptor polymorphisms.

Thurkaa Shanmugalingam,1 Aspasia Soultati,2 Simon Chowdhury,2 Sarah Rudman,2 Mieke Van Hemelrijck11King’s College London, School of Medicine, Division of Cancer Studies, Cancer Epidemiology Group, London, UK; 2Department of Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, UKBackground: Testicular cancer is a rare tumor type accounting for 1% of malignancies in men. It is, however, the most common cancer in young men in Western populations. The incidence of testicular cancer is increasing globally, although a decline in mortality rates has been reported in Western countries. It is important to identify whether the variations in trends observed between populations are linked to genetic or environmental factors.Methods: Age-standardized incidence rates and age-standardized mortality rates for testicular cancer were obtained for men of all ages in ten countries from the Americas, Asia, Europe, and Oceania using the Cancer Incidence in Five Continents (CI5plus) and World Health Organization (WHO) mortality databases. The annual percent change was calculated using Joinpoint regression to assess temporal changes between geographical regions.Results: Testicular cancer age-standardized incidence rates are highest in New Zealand (7.8), UK (6.3), Australia (6.1), Sweden (5.6), USA (5.2), Poland (4.9), and Spain (3.8) per 100,000 men. India, People’s Republic of China, and Colombia had the lowest incidence (0.5, 1.3, and 2.2, respectively) per 100,000 men. The annual percent changes for overall testicular cancer incidence significantly increased in the European countries Sweden 2.4%, (2.2; 2.6); UK 2.9%, (2.2; 3.6); and Spain 5.0%, (1.7; 8.4), Australia 3.0%, (2.2; 3.7), and People’s Republic of China 3.5%, (1.9; 5.1). India had the lowest overall testicular cancer incidence -1.7%, (-2.5; -0.8). Annual percent changes for overall testicular cancer mortality rates were decreasing in all study populations, with the gre