High dietary intake of calcium has been classified as a probable cause of prostate cancer although the mechanism underlying the association between dietary calcium and prostate cancer risk is unclear. The vitamin D receptor (VDR) is a key regulator of calcium absorption. In the small intestine, VDR expression is regulated by the CDX-2 transcription factor, which binds a polymorphic site in the VDR gene promoter. We examined VDR Cdx2 genotype and calcium intake, assessed by a food frequency questionnaire, in 533 African American prostate cancer cases (256 with advanced stage at diagnosis, 277 with localized stage) and 250 African American controls who participated in the California Collaborative Prostate Cancer Study. We examined the effects of genotype, calcium intake, and diet-gene interactions by conditional logistic regression. Compared to men in the lowest quartile of calcium intake, men in the highest quartile had an approximately two-fold increased risk of localized and advanced prostate cancer (odds ratio [OR]= 2.20, 95% confidence interval [CI]= 1.40, 3.46), with a significant dose-response. Poor absorbers of calcium (VDR Cdx2 GG genotype) had a significantly lower risk of advanced prostate cancer (OR= 0.41, 95% CI = 0.19, 0.90). The gene-calcium interaction was statistically significant (p=0.03). Among men with calcium intake below the median (680 mg/day), carriers of the G allele had an approximately 50% decreased risk compared to men with the AA genotype. These findings suggest a link between prostate cancer risk and high intestinal absorption of calcium.

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Background High calcium intake is consistently associated with increased prostate cancer risk in epidemiologic studies. We previously reported that the positive association between calcium intake and risk of aggressive prostate cancer was modified by the Vitamin D Receptor (VDR) calcium absorption genotype, Cdx2, among African American men. Methods We expanded our previous study to include White men, a population with a higher calcium intake and a higher prevalence of the low absorption allele. We also examined VDR polymorphisms at other loci unrelated to calcium absorption. The study included 1,857 prostate cancer cases (1,140 with advanced stage at diagnosis, 717 with localized stage) and 1,096 controls. Odds ratios (OR) were estimated using conditional logistic regression. Results Among both Blacks and Whites, we observed a threshold for calcium intake (604 mg/day) below which prostate cancer risk declined sharply. Low calcium intake was most strongly associated with decreased risk among men with the VDR Cdx2 low calcium absorption genotype (p for interaction = 0.001 and p=0.06 for Whites and African Americans, respectively). Among all men with this genotype, those in the lowest quartile of calcium intake (<=604 mg/day) had a 50% reduction in risk compared to those in the upper three quartiles (OR=0.49, 95% CI=0.36–0.67). The association between calcium intake and prostate cancer risk was not modified by genotype at other VDR loci. Conclusions and Impact Our findings support the hypothesis that genetic determinants of calcium absorption influence prostate cancer risk and may contribute to racial disparities in prostate cancer incidence and mortality rates.

Global trade has increased nearly 100-fold since 1950, according to the World Trade Organization. Today, major changes in trade are occurring with the advent of mega-ships that can transport thousands more containers than cargo ships now in use. Because global trade is expected to increase dramatically, the railroad industry—in the U.S. alone—has invested more than $5 billion a year over the past decade to expand rail yards and enhance rail routes to transport goods from ports to retail destinations. This article describes cancer risks for residents living in close proximity to rail yards with emissions of diesel particulate matter pollution from locomotives, trucks and yard equipment. The article examines the demographics (income, race/ethnicity) of populations living in the highest estimated cancer risk zones near 18 major rail yards in California, concluding that the majority are over-represented by either lower-income or minority residents (or both). The authors also describe a review of the news media and environmental impact reports to determine if rail yards are still being constructed or expanded in close proximity to homes and schools or in working class/working poor communities of color. The paper suggests policy efforts that might provide more public health protection and result in more “environmentally just” siting of rail yards. The authors conclude that diesel pollution from rail yards, which creates significant diesel cancer risks for those living near the facilities, is an often overlooked public health, health disparities and environmental justice issue in the U.S. The conclusions are relevant to other countries where international trade is increasing and large new intermodal rail facilities are being considered.