Carcinogenesis Advance Access originally published online on March 28, 2008
Carcinogenesis 2008 29(5):999-1004; doi:10.1093/carcin/bgn081
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Sequence variants of elaC homolog 2 (Escherichia coli) (ELAC2) gene and susceptibility to prostate cancer in the Health Professionals Follow-Up Study
1 Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
2 Research Center for Genes, Environment and Human Health and Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei 10020, Taiwan
3 Department of Nutrition
4 Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
* To whom correspondence should be addressed. Tel: +1 617 525 2279; Fax: +1 617 525 2008; Email: karen.chen{at}channing.harvard.edu
Two non-synonymous single-nucleotide polymorphisms (SNPs), Ser217Leu and Ala541Thr, in the elaC homolog 2 (Escherichia coli) (ELAC2) gene have been related to prostate cancer risk in previous studies, though with inconsistent results. The association of ELAC2 haplotypes with prostate cancer risk has not yet been explored. We assessed whether sequence variants in ELAC2 were associated with the risk of total or aggressive prostate cancer. In a nested case–control design within the Health Professionals Follow-Up Study, we identified 659 participants with prostate cancer diagnosed after they provided a blood specimen in 1993 and before January 2000. Controls were 656 age-matched men without prostate cancer who had had a prostate-specific antigen test after providing a blood specimen. We genotyped eight tagging SNPs in ELAC2 to test for the association between sequence variances in ELAC2 and prostate cancer. No individual SNP (including Ser217Leu) was associated with the risk of prostate cancer. Ala541Thr is a rare SNP in this population. One common haplotype (hap4) was statistically significantly associated with an increased risk of prostate cancer [odds ratio (OR) = 1.39, 95% confidence interval = 1.05–1.85]. Two common promoter SNPs and three common haplotypes were statistically significantly associated with aggressive prostate cancer (carriers versus non-carriers—snp2: OR = 1.43, snp3: OR = 0.69, hap1: OR = 1.47, hap2: OR = 0.72, hap4: OR = 1.51; global P-value for all common haplotypes = 0.11). Common SNPs and haplotypes of ELAC2 were associated with risk of aggressive prostate cancer.
Abbreviations: BMI, body mass index; CI, confidence interval; ELAC2, elaC homolog 2 (Escherichia coli); OR, odds ratio; QC, quality control; SNP, single-nucleotide polymorphism