5-lipoxygenase and 5-lipoxygenase-activating protein gene polymorphisms, dietary linoleic acid, and risk for breast cancer.
The n-6 polyunsaturated fatty acid 5-lipoxygenase pathway has been shown to play a role in the carcinogenesis of breast cancer. We conducted a population-based case-control study among Latina, African-American, and White women from the San Francisco Bay area to examine the association of the 5-lipoxygenase gene (ALOX5) and 5-lipoxygenase-activating protein gene (ALOX5AP) with breast cancer risk. Three ALOX5AP polymorphisms [poly(A) microsatellite, -4900 A>G (rs4076128), and -3472 A>G (rs4073259)] and three ALOX5 polymorphisms [Sp1-binding site (-GGGCGG-) variable number of tandem repeat polymorphism, -1279 G>T (rs6593482), and 760 G>A (rs2228065)] were genotyped in 802 cases and 888 controls. We did not find significant main effects of ALOX5 and ALOX5AP genotypes on breast cancer risk that were consistent across race or ethnicity; however, there was a significant interaction between the ALOX5AP -4900 A>G polymorphism and dietary linoleic acid intake (P=0.03). Among women consuming a diet high in linoleic acid (top quartile of intake, >17.4 g/d), carrying the AA genotype was associated with higher breast cancer risk (age- and race-adjusted odds ratio, 1.8; 95% confidence interval, 1.2-2.9) compared with carrying genotypes AG or GG. Among women consuming <or=17.4 g/d of linoleic acid, ALOX5AP -4900 genotype was not associated with breast cancer risk (age- and race-adjusted odds ratio, 0.9; 95% confidence interval, 0.7-1.2). These results support a role for n-6 polyunsaturated fatty acids in breast carcinogenesis and suggest that epidemiologic studies on dietary fat and breast cancer should take into account genetic predisposition related to n-6 polyunsaturated fatty acid metabolism.
Wang
Jun
J
Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. jwang1@tuftsmedicalcenter.org
John
Esther M
EM
Ingles
Sue Ann
SA
D058927:5-Lipoxygenase-Activating Proteins; D001741:Black or African American / Q000706:statistics & numerical data; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D019787:Linoleic Acid / Q000008:administration & dosage* / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012042:Registries; D012307:Risk Factors; D012495:San Francisco / Q000453:epidemiology; D011795:Surveys and Questionnaires; D020080:Tandem Repeat Sequences; D044465:White People / Q000706:statistics & numerical data
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; D019787:Linoleic Acid; D001094:Arachidonate 5-Lipoxygenase