Genetic polymorphisms in the apoptosis-associated genes FAS and FASL and breast cancer risk.
FAS and FAS ligand (FASL) play key roles in apoptotic signaling and down-regulation of this pathway may facilitate tumorigenesis. Alterations in apoptosis genes may affect cancer risk by influencing individual susceptibility to environmental carcinogens. Using a population-based breast cancer case-control study on Long Island, New York, we examined whether polymorphisms in FAS and FASL modified the association between breast cancer risk and a marker of environmental exposures, polycyclic aromatic hydrocarbon (PAH)-DNA adducts. We examined polymorphisms in FAS (5' UTR -1377G/A and 5' UTR -670G/A) and FASL (5' UTR -844C/T) in 1053 breast cancer cases and 1102 population-based controls. There was no significant association between these genetic polymorphisms and breast cancer risk. The presence of at least one variant allele (GA or AA) in FAS1377 was associated with a 36% increase in breast cancer risk among those with detectable PAH-DNA adduct levels [odds ratio (OR) = 1.36, 95% confidence interval (CI) = 1.01-1.83]. In addition, lactation history significantly modified the association between FAS1377 and FAS670 genetic variants and breast cancer risk (OR = 1.46, 95% CI = 1.04-2.06 and OR = 1.71, 95% CI = 1.13-1.58, respectively, in those who ever lactated compared with those who did not with the wild-type alleles). Overall, this study suggests that the risk of breast cancer may be elevated among women with polymorphisms in the FAS gene and detectable PAH-DNA adducts.
Crew
Katherine D
KD
Department of Medicine and the Herbert Irving Comprehensive Cancer Center, Columbia University, 161 Fort Washington Avenue, 10-1072, New York, NY 10032, USA. kd59@columbia.edu
Gammon
Marilie D
MD
Terry
Mary Beth
MB
Zhang
Fang Fang
FF
Agrawal
Meenakshi
M
Eng
Sybil M
SM
Sagiv
Sharon K
SK
Teitelbaum
Susan L
SL
Neugut
Alfred I
AI
Santella
Regina M
RM
D020121:5' Untranslated Regions; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D017209:Apoptosis; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D003278:Contraceptives, Oral, Hormonal / Q000008:administration & dosage; D018736:DNA Adducts / Q000032:analysis; D004781:Environmental Exposure; D015914:Estrogen Replacement Therapy; D053222:Fas Ligand Protein / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007774:Lactation; D009518:New York / Q000453:epidemiology; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis; D011110:Polymorphism, Genetic; D012306:Risk; D014029:Tobacco Use Disorder; D019014:fas Receptor / Q000235:genetics*
D020121:5' Untranslated Regions; D003278:Contraceptives, Oral, Hormonal; D018736:DNA Adducts; C491901:FAS protein, human; D053222:Fas Ligand Protein; D011084:Polycyclic Aromatic Hydrocarbons; D019014:fas Receptor; C095911:polycyclic aromatic hydrocarbons-DNA adduct