Polyunsaturated fatty acids, DNA repair single nucleotide polymorphisms and colorectal cancer in the Singapore Chinese Health Study.
Animal and in vitrostudies support a role for polyunsaturated fatty acids (PUFAs) in colon carcinogenesis; however, the epidemiological evidence is inconclusive. Recently, we investigated their role within the Singapore Chinese Health Study, a population-based cohort of Singapore Chinese men and women. We reported that a high intake of marine n-3 PUFAs was associated with an increased risk of colorectal cancer (CRC). Oxidation of PUFAs incorporated into cell membranes generates lipid hydroperoxides, which can be mutagenic. In this report, we investigated whether single nucleotide polymorphisms (SNPs) in DNA repair genes modified the effect of PUFAs on CRC risk using a nested case-control study within the Singapore Chinese Health Study. We genotyped 1,181 controls and 311 cases (180 colon and 131 rectal cancer) for SNPs in the XRCC1 (Arg194Trp, Arg399Gln), OGG1 (Ser326Cys), PARP (Val762Ala, Lys940Arg), and XPD (Asp312Asn, Lys751Gln) genes. We observed that the PARP Val762Ala SNP modified the association between marine n-3 PUFA and rectal cancer risk, with no evidence of interaction among colon cancer (heterogeneity test p=0.003). Our results suggest a positive association between high intake of marine n-3 PUFA and rectal cancer risk among carriers of at least one PARP codon 762 Ala allele (odds ratio=1.7, 95% confidence interval=1.1-2.7).
Stern
Mariana C
MC
Department of Preventive Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA. marianas@usc.edu
Butler
Lesley M
LM
Corral
Román
R
Joshi
Amit D
AD
Yuan
Jian-Min
JM
Koh
Woon-Puay
WP
Yu
Mimi C
MC
D000368:Aged; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D002681:China / Q000453:epidemiology; D003110:Colonic Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012004:Rectal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D011065:Poly(ADP-ribose) Polymerases