Genetic variants in frizzled-related protein (FRZB) and the risk of colorectal neoplasia.
OBJECTIVE
The Wnt/APC/beta-catenin signaling pathway, which includes frizzled-related protein (FRZB), plays a critical role in the development of colorectal cancer, and recent evidence suggests that the functional polymorphism, FRZB Arg324Gly, may be associated with risk for this disease. To determine if this finding could be replicated, we investigated the association between two FRZB polymorphisms (Arg324Gly and Arg200Trp) and the risk of colorectal adenoma and cancer in nested case-control studies.


METHODS
Participants consisted of 1,709 adenoma cases, 620 cancer cases, and 1,849 controls within the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations with colorectal neoplasia.


RESULTS
No association was observed for either polymorphism or any haplotypes with colorectal adenoma or colorectal cancer (p>0.05 for all).


CONCLUSIONS
Our study does not support the previously observed association between the FRZB 324Gly variant and colorectal cancer risk. However, further study of additional genetic variants within this pathway is still warranted, given the important role of the Wnt signaling pathway in colorectal carcinogenesis.
Berndt
Sonja I
SI
Division of Cancer Epidemiology & Genetics, National Cancer Institute, 6120 Executive Blvd, EPS 8116, MSC 7240, Bethesda, MD 20892-7240, USA. berndts@mail.nih.gov
Huang
Wen-Yi
WY
Yeager
Meredith
M
Weissfeld
Joel L
JL
Chanock
Stephen J
SJ
Hayes
Richard B
RB
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D001741:Black or African American; D000465:Algorithms; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016001:Confidence Intervals; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D055088:Early Detection of Cancer; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005998:Glycine / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics*; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008403:Mass Screening; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012812:Sigmoidoscopy; D014364:Tryptophan / Q000378:metabolism; D044465:White People; D000099274:Frizzled-Related Proteins
D004273:DNA, Neoplasm; D005998:Glycine; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D014364:Tryptophan; D000099274:Frizzled-Related Proteins