title: Genetic variation in selenoprotein genes, lifestyle, and risk of colon and rectal cancer.
abstract: BACKGROUND
  Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process.
  
  
  METHODS
  We used data from two population-based case-control studies of colon (n = 1555 cases, 1956 controls) and rectal (n = 754 cases, 959 controls) cancer. We evaluated the association between genetic variation in TXNRD1, TXNRD2, TXNRD3, C11orf31 (SelH), SelW, SelN1, SelS, SepX, and SeP15 with colorectal cancer risk.
  
  
  RESULTS
  After adjustment for multiple comparisons, several associations were observed. Two SNPs in TXNRD3 were associated with rectal cancer (rs11718498 dominant OR 1.42 95% CI 1.16,1.74 pACT 0.0036 and rs9637365 recessive 0.70 95% CI 0.55,0.90 pACT 0.0208). Four SNPs in SepN1 were associated with rectal cancer (rs11247735 recessive OR 1.30 95% CI 1.04,1.63 pACT 0.0410; rs2072749 GGvsAA OR 0.53 95% CI 0.36,0.80 pACT 0.0159; rs4659382 recessive OR 0.58 95% CI 0.39,0.86 pACT 0.0247; rs718391 dominant OR 0.76 95% CI 0.62,0.94 pACT 0.0300). Interaction between these genes and exposures that could influence these genes showed numerous significant associations after adjustment for multiple comparisons. Two SNPs in TXNRD1 and four SNPs in TXNRD2 interacted with aspirin/NSAID to influence colon cancer; one SNP in TXNRD1, two SNPs in TXNRD2, and one SNP in TXNRD3 interacted with aspirin/NSAIDs to influence rectal cancer. Five SNPs in TXNRD2 and one in SelS, SeP15, and SelW1 interacted with estrogen to modify colon cancer risk; one SNP in SelW1 interacted with estrogen to alter rectal cancer risk. Several SNPs in this candidate pathway influenced survival after diagnosis with colon cancer (SeP15 and SepX1 increased HRR) and rectal cancer (SepX1 increased HRR).
  
  
  CONCLUSIONS
  Findings support an association between selenoprotein genes and colon and rectal cancer development and survival after diagnosis. Given the interactions observed, it is likely that the impact of cancer susceptibility from genotype is modified by lifestyle.
authors.affiliation: Department of Internal Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah, United States of America. marty.slattery@hsc.utah.edu
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.forename: Abbie
authors.initials: A
authors.lastname: Lundgreen
authors.forename: Bill
authors.initials: B
authors.lastname: Welbourn
authors.forename: Christopher
authors.initials: C
authors.lastname: Corcoran
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001241:Aspirin / Q000009:adverse effects; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality; D015179:Colorectal Neoplasms / Q000235:genetics; D004967:Estrogens / Q000009:adverse effects; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D009765:Obesity / Q000150:complications; D012004:Rectal Neoplasms / Q000235:genetics* / Q000401:mortality; D012306:Risk; D051140:Selenoproteins / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis; D054482:Thioredoxin Reductase 2 / Q000235:genetics; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004967:Estrogens; D009124:Muscle Proteins; C435489:SELENON protein, human; D051140:Selenoproteins; C516127:TXNRD2 protein, human; C500519:TXNRD3 protein, human; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase; D001241:Aspirin