Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer.
Cytochrome P450 1B1 (CYP1B1) participates in the metabolic activation of a number of procarcinogens including benzo[a]pyrene and the hydroxylation of 17beta-estradiol at the C-4 position. In this study, we investigated the association between CYP1B1 genetic polymorphism and breast or lung cancer incidence. The Ala-Ser polymorphism at codon 119 in presumed substrate recognition site 1 was significantly associated with the incidence of breast or squamous cell carcinoma of the lung. On the other hand, Leu-Val polymorphism at codon 432 did not show any association to the cancers. An allele containing both Ala and Leu simultaneously, comprised 75% of alleles among 315 Japanese healthy controls, was significantly inversely associated with breast cancer incidence. When expressed in a recombinant system, this CYP1B1 cDNA showed the lowest 17beta-estradiol 4-hydroxylase activity among four different variant forms of CYP1B1. Thus, inter-individual differences in activation of procarcinogens or metabolism of oestrogen originating from genetic polymorphisms of the human CYP1B1 gene may contribute to the susceptibility of human cancers.
Watanabe
J
J
Laboratory of Cancer Diagnosis and Therapy, Saitama Cancer Center Research Institute Kitaadachi-gun, Japan. jwata@cancer-c.pref.saitama.jp
Shimada
T
T
Gillam
E M
EM
Ikuta
T
T
Suemasu
K
K
Higashi
Y
Y
Gotoh
O
O
Kawajiri
K
K
D000230:Adenocarcinoma / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D018287:Carcinoma, Large Cell / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D002384:Catalysis; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008175:Lung Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012016:Reference Values; D018570:Risk Assessment; D013250:Steroid Hydroxylases / Q000378:metabolism
D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1