Abstract
BackgroundAssociations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process.MethodsWe 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.ResultsAfter 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).ConclusionsFindings 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.
Highlights
Selenoproteins are a class of proteins with the amino acid selenocysteine that contains the active form of selenium [1]
Three SNPs in thioredoxin reductase 1 (TXNRD1), thioredoxin reductase 2 (TXNRD2) and SelN1 were associated with colon cancer, none remained statistically significant after adjustment for multiple comparisons as indicated by the pACT
While SNPs in TXNRD2 and SepX1 did not remain statistically significant after adjustment for multiple comparisons, those in thioredoxin reductase 3 (TXNRD3) and SelN1 were statistically significant after multiple comparison adjustments with pACT
Summary
Selenoproteins are a class of proteins with the amino acid selenocysteine that contains the active form of selenium [1]. Studies reporting associations between selenium and cancer, and colon cancer [2,3], have directed attention to role of selenoproteins in the carcinogenic process. Given the biological properties of selenoproteins and their roles in control of intracellular redox environment, cellular growth, and defense against oxidative stress, it is feasible that other selenoproteins, such as thioredoxin reductase (TXNRD), selenoprotein W (SelW), selenoprotein N (SelN), selenoprotein S (SelS), selenoprotein H (SelH), selenoprotein X (SepX), and 15-kDa selenoprotein (SeP15) may be involved in the carcinogenic process [4,6]. SeP15 is structurally similar to the thioredoxin family It is located primarily in the endoplasmic reticulum and is involved in the induction of apoptosis and exhibits redox activity [1,12]. Associations between selenium and cancer have directed attention to role of selenoproteins in the carcinogenic process
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