title: Association of frequent consumption of fatty fish with prostate cancer risk is modified by COX-2 polymorphism.
abstract: Dietary intake of marine fatty acids from fish may protect against prostate cancer development. We studied this association and whether it is modified by genetic variation in cyclooxygenase (COX)-2, a key enzyme in fatty acid metabolism and inflammation. We assessed dietary intake of fish among 1,499 incident prostate cancer cases and 1,130 population controls in Sweden. Five single nucleotide polymorphisms (SNPs) were identified and genotyped in available blood samples for 1,378 cases and 782 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. Multiplicative and additive interactions between fish intake and COX-2 SNPs on prostate cancer risk were evaluated. Eating fatty fish (e.g., salmon-type fish) once or more per week, compared to never, was associated with reduced risk of prostate cancer (OR: 0.57, 95% CI: 0.43-0.76). The OR comparing the highest to the lowest quartile of marine fatty acids intake was 0.70 (95% CI: 0.51-0.97). We found a significant interaction (p < 0.001) between salmon-type fish intake and a SNP in the COX-2 gene (rs5275: +6365 T/C), but not with the 4 other SNPs examined. We found strong inverse associations with increasing intake of salmon-type fish among carriers of the variant allele (OR for once per week or more vs. never = 0.28, 95% CI: 0.18-0.45; p(trend) < 0.01), but no association among carriers of the more common allele. Frequent consumption of fatty fish and marine fatty acids appears to reduce the risk of prostate cancer, and this association is modified by genetic variation in the COX-2 gene.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. maria.hedelin@ki.se
authors.forename: Maria
authors.initials: M
authors.lastname: Hedelin
authors.forename: Ellen T
authors.initials: ET
authors.lastname: Chang
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.forename: Rino
authors.initials: R
authors.lastname: Bellocco
authors.forename: Asa
authors.initials: A
authors.lastname: Klint
authors.forename: Jan
authors.initials: J
authors.lastname: Adolfsson
authors.forename: Katarina
authors.initials: K
authors.lastname: Shahedi
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Katarina Augustsson
authors.initials: KA
authors.lastname: Bälter
mesh_terms: D000368:Aged; D000818:Animals; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004032:Diet; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005395:Fish Oils / Q000008:administration & dosage*; D005396:Fish Products; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000235:genetics; D012306:Risk; D012474:Salmon; D013548:Sweden / Q000453:epidemiology
chemical_list: D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human