BACKGROUND: The arachidonic acid (AA) pathway is suspected to be involved in the development of various cancers, including prostate cancer. However, the role of single nucleotide polymorphisms (SNPs) of AA pathway genes remains unclear. The purpose of this case-control study was to evaluate the association between prostate cancer risk and 14 such SNPs in the PTGS2, PTGES2, ALOX5, ALOX5AP, and LTA4H genes. METHODS: Genotyping was conducted on 585 white prostate cancer cases and 585 healthy, age-matched controls. The best genetic model for each SNP was determined using Akaike's information criterion. Odds ratios for the association between each SNP and prostate cancer risk were calculated, both overall and stratified by obesity (BMI ≥ 30). Haplotype analysis was conducted for the PTGES2 SNPs. RESULTS: LTA4H rs1978331 was inversely associated with prostate cancer risk overall (unadjusted, overdominant model OR = 0.68, 95% CI: 0.51-0.91 for TC vs. TT/CC). Among non-obese individuals, the GG genotype of PTGES2 rs10987883 was associated with an increased risk for prostate cancer (unadjusted, recessive model OR = 3.23, 95% CI: 1.27-8.23). CONCLUSIONS: Our results indicate that SNPs in certain AA metabolism genes may influence prostate cancer susceptibility. Furthermore, it is possible that obesity, which induces a chronic state of low-level inflammation in addition to several metabolic sequelae, may modify the impact of these SNPs. These findings should be confirmed in a larger study with power to detect differential effects by obesity.
BACKGROUND: The arachidonic acid (AA) pathway is suspected to be involved in the development of various cancers, including prostate cancer. However, the role of single nucleotide polymorphisms (SNPs) of AA pathway genes remains unclear. The purpose of this case-control study was to evaluate the association between prostate cancer risk and 14 such SNPs in the PTGS2, PTGES2, ALOX5, ALOX5AP, and LTA4H genes. METHODS: Genotyping was conducted on 585 white prostate cancer cases and 585 healthy, age-matched controls. The best genetic model for each SNP was determined using Akaike's information criterion. Odds ratios for the association between each SNP and prostate cancer risk were calculated, both overall and stratified by obesity (BMI ≥ 30). Haplotype analysis was conducted for the PTGES2 SNPs. RESULTS:LTA4Hrs1978331 was inversely associated with prostate cancer risk overall (unadjusted, overdominant model OR = 0.68, 95% CI: 0.51-0.91 for TC vs. TT/CC). Among non-obese individuals, the GG genotype of PTGES2rs10987883 was associated with an increased risk for prostate cancer (unadjusted, recessive model OR = 3.23, 95% CI: 1.27-8.23). CONCLUSIONS: Our results indicate that SNPs in certain AA metabolism genes may influence prostate cancer susceptibility. Furthermore, it is possible that obesity, which induces a chronic state of low-level inflammation in addition to several metabolic sequelae, may modify the impact of these SNPs. These findings should be confirmed in a larger study with power to detect differential effects by obesity.
Authors: Sean F Altekruse; Lan Huang; James E Cucinelli; Timothy S McNeel; Kristen M Wells; M Norman Oliver Journal: Cancer Epidemiol Biomarkers Prev Date: 2010-05-25 Impact factor: 4.254
Authors: K Shahedi; S Lindström; S L Zheng; F Wiklund; J Adolfsson; J Sun; K Augustsson-Bälter; B-L Chang; H-O Adami; W Liu; H Grönberg; J Xu Journal: Int J Cancer Date: 2006-08-01 Impact factor: 7.396
Authors: R J Griffiths; E R Pettipher; K Koch; C A Farrell; R Breslow; M J Conklyn; M A Smith; B C Hackman; D J Wimberly; A J Milici Journal: Proc Natl Acad Sci U S A Date: 1995-01-17 Impact factor: 11.205