Genetic polymorphisms in the Paraoxonase 1 gene and risk of ovarian epithelial carcinoma.
Oxidative stress during successive ovulations increases the opportunity for DNA damage to ovarian epithelial cells and the potential for malignant transformation. Paraoxonase 1 (PON1) is an endogenous free radical scavenger that reduces oxidative stress. The association of two common functional single nucleotide polymorphisms (SNP), rs854560 T>A and rs662 A>G, with the risk of epithelial ovarian cancer was examined in a population-based case-control study in Hawaii. A personal interview and blood specimens were collected from 274 women with histologically confirmed, primary ovarian cancer and 452 controls frequency matched on age and ethnicity. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. Both PON1 SNPs were significantly associated with ovarian cancer risk. The ORs were 0.53 (95% CI, 0.35-0.79; P for allele-dose effect = 0.01) for women carrying the rs854560 T allele compared with women with the AA genotype and 0.65 (95% CI, 0.44-0.95; P for allele-dose effect = 0.03) for women carrying the rs662 A allele compared with women with the GG genotype. The association of the rs854560 T genotype with risk was stronger among smokers (OR, 0.33; 95% CI, 0.17-0.64; P for allele-dose effect = 0.0007) than among nonsmokers (OR, 0.68; 95% CI, 0.40-1.18; P for allele-dose effect = 0.53). The decreased risk associated with the rs854560 T allele was also stronger among obese women (OR, 0.19; 95% CI, 0.06-0.55; P for allele-dose effect = 0.007) than among nonobese women (OR, 0.62; 95% CI, 0.40-0.98; P for allele-dose effect = 0.16). Our study provides evidence for an association of two PON1 SNPs with the risk of epithelial ovarian cancer. Possible effect modification of these associations by tobacco smoking and obesity needs confirmation in other studies.
Lurie
Galina
G
Cancer Epidemiology Program, Cancer Research Center of Hawaii, 1236 Lauhala Street, Room 301C, Honolulu, HI 96813, USA. glurie@CRCH.hawaii.edu
Wilkens
Lynne R
LR
Thompson
Pamela J
PJ
McDuffie
Katharine E
KE
Carney
Michael E
ME
Terada
Keith Y
KY
Goodman
Marc T
MT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D043303:Aryldialkylphosphatase / Q000235:genetics*; D016022:Case-Control Studies; D004249:DNA Damage; D005260:Female; D005838:Genotype; D006254:Hawaii / Q000208:ethnology; D006801:Humans; D007407:Interviews as Topic; D016015:Logistic Models; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D018426:SEER Program
D043303:Aryldialkylphosphatase