Sulfotransferase 1A1 (SULT1A1) polymorphism, PAH-DNA adduct levels in breast tissue and breast cancer risk in a case-control study.
Gene-environment interactions are hypothesized to be major contributors to susceptibility to environmental carcinogens and interindividual variability in cancer risk. We present findings on associations between genetic susceptibility due to inherited polymorphisms of the Phase II detoxification enzyme sulfotransferase 1A1 (SULT1A1), breast cancer risk, and polycyclic aromatic hydrocarbon (PAH)-DNA adducts. A hospital based case-control study was conducted at the New York-Presbyterian Medical Center (NYPMC). The study utilized two control groups: one comprised of women with benign breast disease (BBD) and the other comprised of women visiting NYPMC for routine gynecologic checkups (healthy controls). Blood samples were collected from cases and controls; and breast tissue from pathology blocks was collected from cases (tumor and non-tumor tissue) and BBD controls (benign tissue). PAH-DNA adduct levels were measured by immunohistochemistry in breast tissue samples, and the SULT1A1 (Arg/His) polymorphism at codon 213 was determined by PCR RFLP analyses using DNA from white blood cells. Increasing number of His alleles was modestly associated with breast cancer case-control status, when cases were compared to healthy controls (p for trend = 0.08), when cases were compared to BBD controls (p for trend = 0.08) and when cases were compared to both control groups combined (p for trend = 0.07). Contrary to our hypothesis PAH-DNA adduct levels in breast tissue were not associated with SULT1A1 genotype. Our findings are consistent with a prior report that the Arg/His polymorphism in SULT1A1 is associated with breast cancer risk.
Department of Environmental Health Sciences, Joseph L Mailman School of Public Health, Columbia University, New York City, NY 10032, USA.
Deliang
D
Tang
Andrew
A
Rundle
Laverne
L
Mooney
Stan
S
Cho
Freya
F
Schnabel
Alison
A
Estabrook
Amalia
A
Kelly
Richard
R
Levine
Hannina
H
Hibshoosh
Frederica
F
Perera
D015239:Arylsulfotransferase; D001940:Breast / Q000737:chemistry / Q000378:metabolism; D001941:Breast Diseases / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D018736:DNA Adducts / Q000032:analysis / Q000235:genetics*; D004777:Environment; D004781:Environmental Exposure / Q000009:adverse effects; D004967:Estrogens / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis; D011110:Polymorphism, Genetic / Q000235:genetics*; D012306:Risk; D015238:Sulfotransferases / Q000235:genetics*
D018736:DNA Adducts; D004967:Estrogens; D011084:Polycyclic Aromatic Hydrocarbons; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human