Cytochrome P-450 1A1 Gene Polymorphisms and Risk of Breast Cancer: A HuGE Review

Abstract

Cytochrome P-450 (CYP) 1A1 plays a key role in phase I metabolism of polycyclic aromatic hydrocarbons and in estrogen metabolism. It is expressed predominantly in extrahepatic tissues, including the breast. Four CYP1A1 gene polymorphisms (3801T --> C, Ile462Val, 3205T --> C, and Thr461Asp) have been studied in relation to breast cancer. The 3801C variant is more common than the Val variant. Both variants occur more frequently in Asians than in White populations. The 3205T --> C polymorphism has been observed in African Americans only. Little data are available on the geographic/ethnic distribution of the Thr461Asp polymorphism. The functional significance of the polymorphisms is unclear. In 17 studies, no consistent association between breast cancer and CYP1A1 genotype was found. Meta-analysis found no significant risk for the genotypes 1) 3801C/C (relative risk (RR) = 0.97, 95% confidence interval (CI): 0.52, 1.80) or 3801T/C (RR = 0.91, 95% CI: 0.70, 1.19) versus 3801T/T, 2) Val/Val (RR = 1.04, 95% CI: 0.63, 1.74) or Ile/Val (RR = 0.92, 95% CI: 0.76, 1.10) versus Ile/Ile, or 3) Asp/Asp (RR = 0.95, 95% CI: 0.20, 4.49) or Thr/Asp (RR = 1.12, 95% CI: 0.87, 1.43) versus Thr/Thr. Future studies should explore possible interactions between CYP1A1 and sources of polycyclic aromatic hydrocarbons, markers of estrogen exposure, other lifestyle factors influencing hormonal levels, and other genes involved in polycyclic aromatic hydrocarbon metabolism or hormonal biosynthesis.

Combinations of cytochrome P-450 genotypes and risk of early-onset lung cancer in Caucasians and African Americans: A population-based study

“…The two polymorphisms have not been shown to be in linkage disequilibrium [35]. The CYP1A1 Thr 461 Asn SNP has not been associated with lung cancer [35] or breast cancer [34,36] in casecontrol studies. After a review of sequence data from 130 individuals, we found 5 instances (3.3%) where the second SNP was heterozygous; however, in each case the Ile 462 Val locus was homozygous and the call was not affected by the other SNP.…”

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

“…Two mutually linked polymorphisms of the human CYP1A1 gene, the MspI polymorphism (*2A) located in the 3'-flanking region of the gene and the Ile-Val polymorphism (*2B) at amino acid residue 462 in the haeme-binding region, were reported to be associated with susceptibility to tobacco smoking-associated squamous-cell carcinoma of the lung in Japanese populations Kawajiri & Fujii-Kuriyama, 1991;Nakachi et al, 1993;Kawajiri et al, 1996;Masson et al, 2005). However, this association has not been found in other ethnic groups (Tefre et al, 1991;Hirvonen et al, 1992).…”

“…Individuals have different and unique combinations of drug-metabolizing enzymes in their organs (Nebert et al, 1999;Daly, 2003). For example, some people have enzymes that are defective for the activation of PAHs and normal enzymes that detoxicate PAHs, whereas others have normal enzymes that activate PAHs and enzymes that are defective for the detoxication of reactive PAH metabolites (Garte et al, 2001;Murata et al, 2001;Yin et al, 2001;Kiyohara et al, 2002a;Hung et al, 2004;Lodovici et al, 2004;Masson et al, 2005). In these cases, it is difficult to interpret from epidemiological studies which polymorphisms of drug-metabolizing enzymes are involved in susceptibility to human cancer.…”

“…In these cases, it is difficult to interpret from epidemiological studies which polymorphisms of drug-metabolizing enzymes are involved in susceptibility to human cancer. In many cases, individuals have different combinations of polymorphic enzymes that activate and/or detoxicate PAHs and metabolites (Le Marchand et al, 1998;Quiñones et al, 1999;Grzybowska et al, 2000;Nerurkar et al, 2000;Olshan et al, 2000;Kiyohara et al, 2002b;Hashibe et al, 2003;Sarmanova et al, 2004;Masson et al, 2005).…”

Clinical, Cytogenetic and CYP1A1 exon-1 Gene Mutation Analysis of Beedi Workers in Vellore Region, Tamil Nadu

“…The CYP1A1 gene, located at 15q22-q24, comprises seven exons and six introns and spans 5,810 base pairs (Masson et al, 2005). CYP1A1 enzyme belong to cytochrome p450 family, and responsible for the activation of procarcinogens to reactive metabolites (Turesky and Le Marchand, 2011) CYP isoforms metabolize estrogens to catecholoestrogens (CEs), semiquinones and quinines by oxidation reactions.…”