Single nucleotide polymorphisms in Wnt signaling and cell death pathway genes and susceptibility to colorectal cancer.
It is well known that approximately 90% of colorectal cancer (CRC) cases originate from the constitutive activation of the canonical Wnt signaling pathway. There is increasing evidence that genetic variation both in Wnt and apoptotic pathway genes affects CRC susceptibility and progression. This population-based case-control study, including 1795 CRC cases and 1805 controls, investigates the association between common, putative functional polymorphisms in DNFA5, HIF1A, NDRG1, PYGO1, SFRP2, SFRP4, WISP1 and WISP3 genes and CRC risk. We found no evidence for an association between the selected allelic variants and risk of CRC. Subsite analyses, however, revealed a significant association of HIF1A c.*191T>C with rectal cancer risk [odds ratio (OR) = 1.25, 95% confidence interval (CI), 1.03-1.51, P = 0.03] comparing minor allele carriers with major allele homozygotes. In addition, homozygosity for the minor allele of SFRP4 P320T was significantly associated with rectal cancer risk (OR = 1.37, 95% CI, 1.06-1.79, P = 0.02) and early-stage CRC (OR = 1.33, 95% CI, 1.05-1.69, P = 0.02). This study does not support the hypothesis that Wnt signaling- and apoptosis-related polymorphisms contribute to CRC risk. However, our results provide evidence that CRC subsets may be affected. If confirmed, this knowledge may be used to assess individual susceptibility and to target potential measures of cancer prevention.
Frank
Bernd
B
German Cancer Research Center, Heidelberg, Germany. b.frank@dkfz.de
Hoffmeister
Michael
M
Klopp
Norman
N
Illig
Thomas
T
Chang-Claude
Jenny
J
Brenner
Hermann
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D017209:Apoptosis / Q000235:genetics; D002353:Carrier State; D016022:Case-Control Studies; D016923:Cell Death / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005858:Germany; D006720:Homozygote; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012307:Risk Factors; D015398:Signal Transduction; D044465:White People / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics* / Q000502:physiology; D000094742:Secreted Frizzled-Related Proteins
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; C497442:HIF1A protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins