Ethnic differences in estrogen metabolism in healthy women.
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Adult↗
Biomedical subjects
J Trachman
Publications and source records attributed to J Trachman.
A CYP1A1 restriction fragment length polymorphism is associated with breast cancer in African-American women.
We examined the role of CYP1A1 polymorphisms as potential molecular markers of breast cancer susceptibility in Caucasian and African-American women. The case-control study involved 51 women with breast cancer and 269 female controls. In African-Americans, the frequency of the homozygous MspI polymorphism was 3.5% in controls and 19% in breast cancer cases. The odds ratio of breast cancer with the MspI homozygous variant was 9.7 (95% confidence interval: 2.0-47.9). This association was not observed in Caucasian women. The exon 7 and AA polymorphisms were not associated with breast cancer in either group. The mechanism for the observed association between the MspI polymorphism and breast cancer is unclear. It is possible that the CYP1A1 MspI RFLP is linked with other polymorphisms in the African-American population, either in the CYP1A1 gene, which is involved in estrogen metabolism, or other genes related to risk of breast cancer.
Adult↗
A specific African-American CYP1A1 polymorphism is associated with adenocarcinoma of the lung.
A case-control study on lung cancer in African-Americans has been conducted to assess whether a novel African-American-specific polymorphism in the CYP1A1 gene increases the susceptibility to tobacco-related lung cancer. The prevalence of the AA RFLP was 17.1% in the DNA extracted from archived tissue blocks from 76 incident cases of lung cancer, and was 16.3% in peripheral blood lymphocyte DNA of 123 healthy African-American volunteers recruited from a community in the eastern United States. The analysis by histological type showed an association between adenocarcinoma (AC) of the lung and the AA RFLP (odds ratio, 2.6; 95% confidence interval, 1.1-6.3). One homozygous variant subject was present among the AC cases. The risk of AC in subjects who both smoke and carry the AA RFLP was more than double, in comparison to subjects who only smoke (relative interaction magnitude under the additive model, 24%). The mean value of pack-year in AC with the polymorphism was 5.0 +/- 2.5 and in AC without the polymorphism was 37.2 +/- 6.5 (P < 0.05). Our data suggest that a selective association exists between the AA polymorphism and adenocarcinoma of the lung and that a lower dose of tobacco is sufficient to exert carcinogenic effects on the adenomatous tissue of subjects carrying the AA polymorphism.
Adenocarcinoma↗
Radical differences in CYP1A1 genotype and function.
The cytochrome P450 1A1 (CYP1A1) gene may be of critical importance in determining individual cancer susceptibility to aromatic hydrocarbons such as those in tobacco smoke. We compared the frequencies of CYP1A1 haplotypes, and complete genotypes, taking into account polymorphisms at 3 sites, including an African-specific polymorphism. No concordance was observed in Africans or African-Americans between any of the 3 polymorphisms, (Msp1 restriction fragment length polymorphism (RFLP)--'M', exon 7--'E', new RFLP--'A') in contrast to the concordance seen between the M and E polymorphisms in Caucasians and Asians. We observed an effect of the E polymorphism on enzyme activity and mRNA induction in Asians and Caucasians.
Asian People↗
Functional significance of different human CYP1A1 genotypes.
At least two different polymorphisms in the human CYP1A1 gene have been associated with an increased risk for tobacco-related lung cancer; however, the functional significance of these polymorphisms has not been determined. We measured CYP1A1 genotypes, gene expression levels and enzymatic activity levels in mitogen-stimulated lymphocytes to determine whether genetic polymorphisms in CYP1A1 alter transcriptional and/or post-transcriptional regulation of the gene. Genotypes were determined at two sites previously associated with lung cancer: a point mutation in exon 7 near the catalytic region of the enzyme and an Msp1 RFLP in the 3' non-coding region of the gene. Variant genotypes at the Msp1 site had no effect on CYP1A1 gene induction, however, variant genotypes at the exon 7 site were significantly associated with increased CYP1A1 gene inducibility. We also observed a significant interaction between the exon 7 polymorphism and smoking on mRNA levels. There was a 3-fold elevation in CYP1A1 enzymatic activity in exon 7 variant genotypes. When Msp1 and exon 7 genotypes were combined, there was an increased CYP1A1 inducibility and enzymatic activity in subjects with the exon 7 polymorphism, and in subjects with both polymorphisms.
Adult↗
Immunologically reactive proteins of Streptococcus equi.
Immunologically reactive proteins in acid extracts and culture supernatants of Streptococcus equi were recognized through a combination of chromatographic and immunologic procedures. Both high- and low-molecular-weight components of each of these protein preparations were protective for mice and were, therefore, presumed to contain a variety of hydrolytic products or fragments of the M protein of S. equi. Convalescent horse sera that exhibited strong bactericidal activity for S. equi always reacted with polypeptides in the molecular weight range of 24,000 to 29,000, whereas preinfection sera did not. Rabbit antisera to affinity-purified S. equi protein also reacted with these polypeptides, as well as with a polypeptide of about 36,000 to 37,000 molecular weight. M protein in acid extract and culture supernatant did not cross-react in immunodiffusion, but rabbit antiserum to affinity-purified M protein from an acid extract of S. equi reacted strongly with culture supernatant proteins of approximate molecular weights of 67,000, 58,000, and 43,000. We suggest, therefore, that the M protein in culture supernatant is masked by other sequences that are removed by hot acid during preparation of acid extracts. Polypeptides common to acid extracts of S. equi and Streptococcus zooepidemicus were also identified. These polypeptides had molecular weights of about 55,000 and 31,000.
Animals↗
Distribution of composite CYP1A1 genotypes in Africans, African-Americans and Caucasians.
We present the genotype distribution of the CYP1A1 gene in a sample of over 300 subjects of various ethnic origins. Genotypes are presented as composites of eight possible alleles, taking into account the three major polymorphisms, including a recently described African-American-specific MspI RFLP. A new nomenclature system is presented for clarifying the various haplotypes. Interesting interracial differences in allelic frequencies and admixture rates were observed for the three polymorphisms. Because of the importance of the CYP1A1 gene (which encodes the aromatic hydrocarbon hydroxylase) as a biomarker of genetic susceptibility to environmental carcinogens such as polycyclic aromatic hydrocarbons, these data may provide a useful reference for future studies of relationships between CYP1A1 genotype and disease susceptibility.
Africa, Western↗