title: Genetic variation in vitamin D-related genes and risk of colorectal cancer in African Americans.
abstract: OBJECTIVE
  Disparities in both colorectal cancer (CRC) incidence and survival impact African Americans (AAs) more than other US ethnic groups. Because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels, genetic variants that modulate the levels of active hormone in the tissues could explain some of the cancer health disparity. Consequently, we hypothesized that genetic variants in vitamin D-related genes are associated with CRC risk.
  
  
  METHODS
  To test this hypothesis, we studied 39 potentially functional single-nucleotide polymorphisms (SNPs) in eight genes (CYP2R1, CYP3A4, CYP24A1, CYP27A1, CYP27B1, GC, DHCR7, and VDR) in 961 AA CRC cases and 838 healthy AA controls from Chicago and North Carolina. We tested whether SNPs are associated with CRC incidence using logistic regression models to calculate p values, odds ratios, and 95 % confidence intervals. In the logistic regression, we used a log-additive genetic model and used age, gender, and percent West African ancestry, which we estimated with the program STRUCTURE, as covariates in the models.
  
  
  RESULTS
  A nominally significant association was detected between CRC and the SNP rs12794714 in the vitamin D 25-hydroxylase gene CYP2R1 (p = 0.019), a SNP that has previously been associated with serum vitamin D levels. Two SNPs, rs16847024 in the GC gene and rs6022990 in the CYP24A1 gene, were nominally associated with left-sided CRC (p = 0.015 and p = 0.018, respectively).
  
  
  CONCLUSIONS
  Our results strongly suggest that genetic variation in vitamin D-related genes could affect CRC susceptibility in AAs.
authors.affiliation: Department of Pediatrics and the Institute of Human Genetics, University of Illinois at Chicago, 900 S. Ashland Ave. MC 767, Chicago, IL, 60607, USA.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pibiri
authors.forename: Rick A
authors.initials: RA
authors.lastname: Kittles
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sandler
authors.forename: Temitope O
authors.initials: TO
authors.lastname: Keku
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Kupfer
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Xicola
authors.forename: Xavier
authors.initials: X
authors.lastname: Llor
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Ellis
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D015179:Colorectal Neoplasms / Q000097:blood / Q000208:ethnology* / Q000235:genetics*; D000072467:Cytochrome P450 Family 2; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014807:Vitamin D / Q000097:blood / Q000235:genetics*
chemical_list: D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase