Vitamin D binding protein and risk of renal cell carcinoma in the prostate, lung, colorectal and ovarian cancer screening trial

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155964/1/ijc32758.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155964/2/ijc32758_am.pd

Differences in prostate tumor characteristics and survival among religious groups in Songkhla, Thailand

Abstract Background The incidence and mortality from prostate cancer is expected to increase in the next decade in Thailand. Despite the perceived lower risk in this population vs. developed, western countries, it is becoming an important public health issue. Prostate cancer incidence varies between the most predominant religious groups in Thailand, Buddhists and Muslims. However limited data is available describing the prostate cancer survival in these two populations. Here we examine differences in prostate tumor characteristics and survival between Buddhists and Muslims in the province of Songkhla, Thailand. Methods 945 incident prostate cancer cases (1990–2014) from the population-based Songkhla Cancer Registry were used in this analysis. Age, grade, stage, and year at diagnosis were compared across religious groups, using Wilcoxon or Chi-square tests. Kaplan Meier methods were used to estimate the median survival time and 5-year survival probabilities. Cox proportional hazards models were used to estimate hazard ratios (HR) between religious groups and 95% confidence intervals (CI) for mortality in age-adjusted and fully-adjusted models. Results Prostate tumor characteristics, age, and year at diagnosis were similar across religious groups. The median survival time after diagnosis of prostate cancer was longer in Buddhists 3.8 years compared with Muslims 3.2 years (p = 0.08). The age-adjusted risk of death after prostate cancer diagnosis was higher in Muslims compared with Buddhists (HR: 1.31; 95%CI: 1.00, 1.72). After adjustment by stage and grade, results were slightly attenuated (HR: 1.27, 95%CI: 0.97, 1.67). Conclusion Muslims have shorter survival after prostate cancer diagnosis than do Buddhists in Thailand. The reasons underlying this difference require additional investigation in order to design targeted interventions for both populations.https://deepblue.lib.umich.edu/bitstream/2027.42/146539/1/12885_2018_Article_5102.pd

Metabolomic analysis of prostate cancer risk in a prospective cohort: The alpha‐tocolpherol, beta‐carotene cancer prevention (ATBC) study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113106/1/ijc29576.pd

Prospective serum metabolomic profiling of lethal prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152026/1/ijc32218.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152026/2/ijc32218_am.pd

Family history of cancer and head and neck cancer survival

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137774/1/lary26524_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137774/2/lary26524.pd

Serum Metabolomic Response to Long-Term Supplementation with all-rac

Background. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however. Objective. We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all-rac-α-tocopheryl acetate (ATA), 20 mg/day β-carotene, both, placebo). Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.). Results. After correction for multiple comparisons, five metabolites were statistically significantly altered (β is the change in metabolite level expressed as number of standard deviations on the log scale): α-CEHC sulfate (β=1.51, p=1.45×10-38), α-CEHC glucuronide (β=1.41, p=1.02×10-31), α-tocopherol (β=0.97, p=2.22×10-13), γ-tocopherol (β=-0.90, p=1.76×10-11), and β-tocopherol (β=-0.73, p=9.40×10-8). Glutarylcarnitine, beta-alanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation (β range 0.40 to −0.36), but not statistically significantly. Conclusions. Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC)

Study, a randomized controlled cancer prevention trial, showed a 32% reduction in prostate cancer incidence in response to vitamin E supplementation. Two other trials were not confirmatory, however. Objective. We compared the change in serum metabolome of the ATBC Study participants randomized to receive vitamin E to those who were not by randomly selecting 50 men from each of the intervention groups (50 mg/day all-rac--tocopheryl acetate (ATA), 20 mg/day -carotene, both, placebo). Methods. Metabolomic profiling was conducted on baseline and follow-up fasting serum (Metabolon, Inc.). Results. After correction for multiple comparisons, five metabolites were statistically significantly altered ( is the change in metabolite level expressed as number of standard deviations on the log scale): -CEHC sulfate ( = 1.51, = 1.45 × 10 −38 ), -CEHC glucuronide ( = 1.41, = 1.02 × 10 −31 ), -tocopherol ( = 0.97, = 2.22 × 10 −13 ), -tocopherol ( = −0.90, = 1.76 × 10 −11 ), and -tocopherol ( = −0.73, = 9.40 × 10 −8 ). Glutarylcarnitine, betaalanine, ornithine, and N6-acetyllysine were also decreased by ATA supplementation ( range 0.40 to −0.36), but not statistically significantly. Conclusions. Comparison of the observed metabolite alterations resulting from ATA supplementation to those in other vitamin E trials of different populations, dosages, or formulations may shed light on the apparently discordant vitamin E-prostate cancer risk findings

Higher carbohydrate intake is associated with increased risk of allâ cause and diseaseâ specific mortality in head and neck cancer patients: results from a prospective cohort study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145268/1/ijc31413.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145268/2/ijc31413-sup-0001-suppinfo01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145268/3/ijc31413_am.pd

Circulating vitamin D concentration and risk of seven cancers: Mendelian randomisation study

Objective To determine if circulating concentrations of vitamin D are causally associated with risk of cancer.Design Mendelian randomisation study.Setting Large genetic epidemiology networks (the Genetic Associations and Mechanisms in Oncology (GAME-ON), the Genetic and Epidemiology of Colorectal Cancer Consortium (GECCO), and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortiums, and the MR-Base platform).Participants 70 563 cases of cancer (22 898 prostate cancer, 15 748 breast cancer, 12 537 lung cancer, 11 488 colorectal cancer, 4369 ovarian cancer, 1896 pancreatic cancer, and 1627 neuroblastoma) and 84 418 controls.Exposures Four single nucleotide polymorphisms (rs2282679, rs10741657, rs12785878 and rs6013897) associated with vitamin D were used to define a multi-polymorphism score for circulating 25-hydroxyvitamin D (25(OH)D) concentrations.Main outcomes measures The primary outcomes were the risk of incident colorectal, breast, prostate, ovarian, lung, and pancreatic cancer and neuroblastoma, which was evaluated with an inverse variance weighted average of the associations with specific polymorphisms and a likelihood based approach. Secondary outcomes based on cancer subtypes by sex, anatomic location, stage, and histology were also examined.Results There was little evidence that the multi-polymorphism score of 25(OH)D was associated with risk of any of the seven cancers or their subtypes. Specifically, the odds ratios per 25 nmol/L increase in genetically determined 25(OH)D concentrations were 0.92 (95% confidence interval 0.76 to 1.10) for colorectal cancer, 1.05 (0.89 to 1.24) for breast cancer, 0.89 (0.77 to 1.02) for prostate cancer, and 1.03 (0.87 to 1.23) for lung cancer. The results were consistent with the two different analytical approaches, and the study was powered to detect relative effect sizes of moderate magnitude (for example, 1.20-1.50 per 25 nmol/L decrease in 25(OH)D for most primary cancer outcomes. The Mendelian randomisation assumptions did not seem to be violated.Conclusions There is little evidence for a linear causal association between circulating vitamin D concentration and risk of various types of cancer, though the existence of causal clinically relevant effects of low magnitude cannot be ruled out. These results, in combination with previous literature, provide evidence that population-wide screening for vitamin D deficiency and subsequent widespread vitamin D supplementation should not currently be recommended as a strategy for primary cancer prevention

Genome-wide association study identifies common variants associated with circulating vitamin E levels

In genome-wide association studies (GWAS) of common genetic variants associated with circulating alpha- and gamma-tocopherol concentrations in two adult cohorts comprising 5006 men of European descent, we observed three loci associated with alpha-tocopherol levels, two novel single-nucleotide polymorphisms (SNPs), rs2108622 on 19pter-p13.11 (P= 1.7 × 10−8) and rs11057830 on 12q24.31 (P= 2.0 × 10−8) and confirmed a previously reported locus marked by rs964184 on 11q23.3 (P= 2.7 × 10−10). The three SNPs have been reported to be associated with lipid metabolism and/or regulation. We replicated these findings in a combined meta-analysis with two independent samples, P= 7.8 × 10−12 (rs964184 on 11q23.3 near BUD13, ZNF259 and APOA1/C3/A4/A5), P= 1.4 × 10−10 (rs2108622 on 19pter-p13.11 near CYP4F2) and P= 8.2 × 10−9 (rs11057830 on 12q24.31 near SCARB1). Combined, these SNPs explain 1.7% of the residual variance in log alpha-tocopherol levels. In one of the two male GWAS cohorts (n= 992), no SNPs were significantly associated with gamma-tocopherol concentrations after including data from the replication sample for 71 independent SNPs with P< 1 × 10−4 identified