Data suggest that estrogen-metabolizing genes may be involved in breast cancer carcinogenesis.
Objective
The aim of this study was to determine the association of CYP1A1 and COMT polymorphisms with this disease. Material and methods: A pilot case-control study was conducted with Mexican women. Ninety-one breast cancer patients and 94 healthy controls were selected. Epidemiological and clinical questionnaires were answered by all participants, and genotyping data were obtained. CYP1A1 3801 T>C (rs4646903), CYP1A1 4889 A>G (rs1048943) and COMT 1947 G>A (rs4680) polymorphisms were analyzed by PCR-RFLP.
Results
The results showed a high risk of breast cancer in women carrying the CYP1A1 (3801 T>C) m2/m2 genotype (OR=2.52; 95%CI=1.04–6.08). The risk was higher in postmenopausal women (OR=3.38; 95%CI=1.05–10.87). No association between COMT 1947 G>A (rs4680) or CYP1A1 4889 A>G (rs1048943) and breast cancer was found.
Conclusions
This study suggests that the CYP1A1 (3801 T>C) m2/m2 genotype may contribute to breast cancer susceptibility in Mexican women.
VadlamuriS.V., GloverD.D., TurnerT., SarkarM.A.Region specific expression of cytochrome P4501A1 and 1B1 in human uterine tissue.Cancer Lett1998; 122: 143–50.
4.
PerssonI., JohanssonI., Ingelman-SundbergM.In vitro kinetics of two human CYP1A1 variant enzymes suggested to be associated with interindividual differences in cancer susceptibility.Biochem Biophys Res Commun1997; 231: 227–30.
5.
LachmanH.M., PapolosD.F., SaitoY., YuY.M., SzumlanskiC.L., WeinshilboumR.M.: Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neurospsychiatric disorders.Pharmacogenetics1996: 6: 243–50.
6.
HuangC.S., ChernH.D., ChangK.L.Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1 and COMT: a multigenic study on cancer susceptibility.Cancer Res1999; 59: 4870–5.
7.
WenW., CaiQ., ShuX.O.Cytochrome P450 1B1 and catechol-O-methyltransferase genetic polymorphisms and breast cancer risk in Chinese women: results from the Shanghai breast cancer study and a meta-analysis.Cancer Epidemiol Biomarkers Prev2005; 14: 329–35.
8.
HayashiS.I., WatanabeJ., NakachiK., KawajiriK.Genetic linkage of lung cancer-associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IAI gene.J Biochem1991; 110: 407–11.
9.
OyamaT., MitsudomiT., KawamotoT.Detection of CYP1A1 gene polymorphism using designed RFLP and distributions of CYP1A1 genotypes in Japanese.Int Arch Occup Environ Health1995; 67: 253–6.
10.
LiT., ValladaH., CurtisD.Catechol-O-methyltransferase Val 158 Met polymorphism: frequency analysis in Chinese subjects and allelic association of the low activity allele with bipolar affective disorder.Pharmacogenetics1997; 7: 349–53.
11.
BrintonL.A., SchairerC., HooverR.N.Menstrual factors and risk of breast cancer.Cancer Invest1988; 6: 245–54.
12.
BradburyB.D., WilkJ., AschengrauA., LashT.L.Departure from multiplicative interaction for catechol-O-methyltransferase genotype and active/passive exposure to tobacco smoke among women with breast cancer.J Carcinog2006; 5: 3–11.
13.
ShenY., LiD.K., WuJ., ZhangZ., GaoE.Joint effects of the CYP1A1 MspI, Era PvuII, and Era XbaI polymorphisms on the risk of breast cancer: results from a population-based case-control study in Shanghai, China.Cancer Epidemiol Biomarkers Prev2006; 15: 342–7.
14.
LandiM.T., BertazziP.A., ShieldP.G.Association between CYP1A1 genotype, mRNA expression and enzymatic activity in humans.Pharmacogenetics1994; 4: 242–6.
15.
PetersenD.D., McKinneyC.E., IkeyaK.Human CYP1A1 gene: congregation of the enzyme inducibility phenotype and an RFLP.Am J Hum Genet1991; 48: 720–5.
16.
LiY., MillicanR.C., BellD.A.Cigarette smoking, cytochrome P4501A1 polymorphisms and breast cancer among African-American and white women.Breast Cancer Res2004; 6: R460–73.
17.
HuangC.S., ChernH.D., ChangK.J., ChengC.W., HsuS.M., ShenC.Y.Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1 and COMT: a multigenic study on cancer susceptibility.Cancer Res1999; 59: 4870–5.
18.
BoyapatiS.M., ShuX.O., GaoY.T., CaiQ., JinF., ZhengW.Polymorphism in CYP1A1 and breast cancer carcinoma risk in a population-based case-control study of Chinese women.Cancer2005; 103: 2228–35.
19.
ShingV., RastogiN., SinhaA., KumarA., MathurN., SinghM.P.A study on the association of cytochrome-P450 1A1 polymorphism and breast cancer risk in north Indian women.Breast Cancer Res Treat2007; 101: 73–81.
20.
Gallegos-ArreolaM.P., Figuera-VillanuevaL.E., Troyo-SanromanR.CYP1A1 *2B and *4 polymorphisms are associated with lung cancer susceptibility in Mexican patients.Int J Biol Markers2008; 23: 24–30.
21.
Juarez-CedilloT., VallejoM., FragosoJ.M.The risk of developing cervical cancer in Mexican women is associated to CYP1A1 MspI polymorphism.Eur J Cancer2007; 43: 1590–5.
22.
Pereira SerafimP.V., Cotrim Guerreiro da SilvaI.D., Manoukias ForonesN.Relationship between genetic polymorphism of CYP1A1 at codon 462 (Ile462Val) in colorectal cancer.Int J Biol Markers2008; 23: 18–23.
