Molecular epidemiology of breast cancer: a review.
The standard paradigm providing a general mechanistic explanation for the association of cumulative, excessive oestrogen exposure and breast cancer risk is that the proliferative stimulus provided by 17 beta-estradiol (E2) leads to the appearance of spontaneous mutations. Thus, the key contribution of E2 is the stimulation of breast epithelial cell proliferation. However, mounting evidence supports a complimentary pathway involving direct (oestrogen-quinone DNA adducts) and indirect (oxidative DNA damage via redox cycling) genotoxicity originating from oestrogen metabolites. While mutations in high penetrance genes such as BRCA1, BRCA2 and p53 confer a high risk for an individual, they represent a low overall attributable risk due to low allele frequencies in the population. On the other hand, mutations in phases I and II enzyme genes involved in xenobiotic and endobiotic metabolism, including genes encoding CYP1A1, N-acetyltransferase 2 and glutathione-S-transferase (GST) isoforms M1 (null), T1 (null), and P1 (low-activity allele), might confer a low relative cancer risk for an individual. However, because these mutations seem to be common among individuals, they represent a high attributable risk category of genes. The intent of this review is to examine current literature on the molecular epidemiology of breast cancer with emphasis on the role of polymorphisms in high and low penetrance genes on susceptibility to breast cancer.
Okobia
M N
MN
Department of Surgery, College of Medical Sciences, University of Benin, Benin City, Nigeria.
Bunker
C H
CH
D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004249:DNA Damage; D045643:DNA Repair Enzymes / Q000235:genetics; D004967:Estrogens / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008780:Methyltransferases / Q000235:genetics; D017720:Molecular Epidemiology; D009549:Nigeria / Q000453:epidemiology; D011110:Polymorphism, Genetic; D013482:Superoxide Dismutase / Q000235:genetics
D004967:Estrogens; D003577:Cytochrome P-450 Enzyme System; D013482:Superoxide Dismutase; D008780:Methyltransferases; D045643:DNA Repair Enzymes