Association of single nucleotide polymorphisms in glycosylation genes with risk of epithelial ovarian cancer.
Studies suggest that underglycosylation of the cell membrane mucin MUC1 may be associated with epithelial ovarian cancer. We identified 26 genes involved in glycosylation and examined 93 single nucleotide polymorphisms (SNP) with a minor allele frequency of > or =0.05 in relation to incident ovarian cancer. Cases were ascertained at the Mayo Clinic, Rochester, MN (n = 396) or a 48-county region in North Carolina (Duke University; n = 534). Ovarian cancer-free controls (n = 1,037) were frequency matched to the cases on age, race, and residence. Subjects were interviewed to obtain data on risk factors and a sample of blood for DNA and genotyped using the Illumina GoldenGate assay. We excluded subjects and individual SNPs with genotype call rates of <90%. Data were analyzed using logistic regression, with adjustment for age and residence. We fitted dominant, log additive, and recessive genetic models. Among Caucasians, nine SNPs in eight genes were associated with risk at P < 0.05 under at least one genetic model before adjusting for multiple testing. A SNP in GALNT1 (rs17647532) was the only one that remained statistically significant after Bonferroni adjustment for multiple testing but was not statistically significant in Hardy-Weinberg equilibrium among controls. Haplotype analyses revealed a global association of GALNT1 with risk (P = 0.038, under a recessive genetic model), which largely reflected a decreased risk of one haplotype (0.10 frequency; odds ratio, 0.07; P = 0.01) compared with the most common haplotype (0.39 frequency). These results suggest that genetic polymorphisms in the glycoslyation process may be novel risk factors for ovarian cancer.
Sellers
Thomas A
TA
Division of Cancer Prevention and Control, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. sellerta@moffitt.usf.edu
Huang
Yifan
Y
Cunningham
Julie
J
Goode
Ellen L
EL
Sutphen
Rebecca
R
Vierkant
Robert A
RA
Kelemen
Linda E
LE
Fredericksen
Zachary S
ZS
Liebow
Mark
M
Pankratz
V Shane
VS
Hartmann
Lynn C
LC
Myer
Jeff
J
Iversen
Edwin S
ES
Schildkraut
Joellen M
JM
Phelan
Catherine
C
D000704:Analysis of Variance; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D006031:Glycosylation; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D008910:Minnesota; D018396:Mucin-1 / Q000235:genetics*; D009657:North Carolina; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C060192:MUC1 protein, human; D018396:Mucin-1