Semaphorin 3B and 3F single nucleotide polymorphisms are associated with prostate cancer risk and poor prognosis.
OBJECTIVE
SEMA3B and SEMA3F are 2 closely related genes lying 80 kb apart on chromosome 3 that have been shown to suppress tumor formation in vivo and in vitro. Each gene has a single nucleotide polymorphism that results in a nonsynonymous coding change, rs2071203 (SEMA3B) and rs1046956 (SEMA3F), as well as noncoding single nucleotide polymorphisms.


METHODS
We performed a case-control study of 789 prostate cancer cases and 907 controls from 3 races/ethnicities to determine possible associations of 10 variants with prostate cancer risk or prognosis.


RESULTS
The risk of prostate cancer increased more than 2-fold in Hispanic men with TT alleles at rs2071203 in SEMA3B and with CC alleles for rs2072054 at the 5' end of SEMA3F (OR 2.13, 95% CI 1.12-4.04, p = 0.02 and OR 2.55, 95% CI 1.34-4.84, p = 0.0045, respectively). These 2 single nucleotide polymorphisms were also associated with a poor prognosis in Hispanic men (2.71 and 3.48-fold increased risk). A frequent G-C-G-G-A-T-C-C-T-G haplotype encompassing 10 SNPs was associated with an increased risk of prostate cancer and poor prognosis in Hispanic samples (OR 2.72, 95% CI 1.20-6.12, p = 0.016 and OR 3.32, 95% CI 1.21-9.10, p = 0.02). In nonHispanic white men the T-C-G-A-A-T-C-C haplotype was associated with a high Gleason score (OR 1.44, 95% CI 1.06-1.96, p = 0.021).


CONCLUSIONS
These data indicate that polymorphisms in SEMA3B and SEMA3F are associated with prostate cancer risk and poor prognosis in Hispanic and nonHispanic white men.
Beuten
Joke
J
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Garcia
Dawn
D
Brand
Timothy C
TC
He
Xin
X
Balic
Ivana
I
Canby-Hagino
Edith
E
Troyer
Dean A
DA
Baillargeon
Jacques
J
Hernandez
Javier
J
Thompson
Ian M
IM
Leach
Robin J
RJ
Naylor
Susan L
SL
D000328:Adult; D001741:Black or African American; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors; D039961:Semaphorins / Q000235:genetics*; D044465:White People
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C409766:SEMA3B protein, human; C491230:SEMA3F protein, human; D039961:Semaphorins