Modification of Clinical Presentation of Prostate Tumors by a Novel Genetic Variant in CYP3A4

Rebbeck, Timothy R.; Jaffe, Julie M.; Walker, A. H. C.; Wein, Alan J.; Malkowicz, S. Bruce

doi:10.1093/jnci/90.16.1225

Cited by 376 publications

(241 citation statements)

References 13 publications

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“…15 A number of sequence variants at the CYP3A locus have been identified, but few of them have been definitively associated with alterations in mRNA or protein levels and/or CYP3A function. The CYP3A4*1B allele, originally reported to be associated with advanced clinical grade of prostate tumors, 16 is a common SNP located in the 5 0 flanking region. A number of nonsynonymous (ns) SNPs have been reported for CYP3A4, but most occur at low frequency.…”

Section: Introductionmentioning

confidence: 99%

Sequence diversity and haplotype structure at the human CYP3A cluster

et al. 2005

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The four members of the human CYP3A subfamily play important roles in the clearance of xenobiotics, hormones, and environmental compounds. Many SNPs at the CYP3A locus have been characterized, with several showing large allele frequency differences across populations. In addition to the effects of CYP3A SNPs on drug metabolism, recent studies have highlighted the potential for CYP3A variation in susceptibility to several common phenotypes, including hypertension and cancer. We previously showed that the CYP3A4 and CYP3A5 genes have a strong haplotype structure at varying frequencies across ethnic groups. Here, we extend our re-sequencing survey to the remaining CYP3A genes in the same cluster, CYP3A7 and CYP3A43. Our study identified a large number of SNPs in coding and conserved noncoding sequences, several of which are common. The combined data set allows us to investigate patterns of sequence variation and linkage disequilibrium at the entire CYP3A locus for use in future association studies.

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Section: Introductionmentioning

confidence: 99%

Sequence diversity and haplotype structure at the human CYP3A cluster

et al. 2005

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“…33,34 This variant has the highest frequency in African-Americans, mid-frequency in Caucasians, and lowest frequency in Asians, 35,36 re¯ecting relative prostate cancer rates in these populations. The CYP3A4 variant was associated with prostate cancer risk in Caucasians 23 and African-Americans 36 in case ± control studies.…”

Section: Genes Involved In Androgen Metabolism and Regulation In The mentioning

confidence: 96%

The role of candidate genetic polymorphisms in the etiology of prostate cancer

Neuhausen

2000

Prostate Cancer Prostatic Dis

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Prostate cancer appears to result from complex interactions among genetic, endocrine and environmental factors. Identi®cation of risk factors for development and progression of prostate cancer is needed. This will allow researchers to design strategies to reduce the morbidity and mortality from this cancer and to identify individuals at increased risk of developing the disease. It is probable that common genetic polymorphisms (variants) in genes directly and indirectly involved in androgen biosynthesis, metabolism and regulation are important. Other important genes are likely to be those directly involved in regulation of prostate cell proliferation and apoptosis. Prostate Cancer and Prostatic Diseases (2000) 3, 236±240.

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“…In addition, genetic studies have revealed an association between genetic variants of the natural resistance-associated macrophage protein (NRAMP1) and VDR genes and smearpositive pulmonary TB (15). Evidence regarding the 1,25(OH) 2 D3-VDR complex has shown that after binding to the RXR heterodimer, this complex interacts with the PXR response elements on the CYP3A4 gene promoter (12,16). It suggests that CYP3A4 enzymes or signaling involving CYP3A4 may be associated with susceptibility to the development of pulmonary TB.…”

Section: D3] Similarmentioning

confidence: 99%

Unique CYP3A4 genetic variant in Brazilian tuberculosis patients with/without HIV

et al. 2011

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Abstract. CYP3A4 is involved in tuberculosis (TB) and human immunodeficiency virus (HIV) drug metabolism. Transcriptional activation by rifampicin involves the CYP3A4 gene 5'-upstream region. Consequently, variation may interfere with transcription and enzymatic activity and even drug response. However, genetic polymorphisms and distribution of CYP3A4 allelic frequencies in individuals from Rio de Janeiro remain unknown. The aim of this study was to conduct research into sequencing the CYP3A4 5'-upstream region in Brazilian patients with and without HIV. This follow-up study involved 106 individuals undergoing treatment for TB and/ or HIV. The CYP3A4 5'-upstream region was analyzed using PCR, sequencing and clinical data. Male patients revealed a higher HIV frequency (p=0.021). The TB forms observed were pulmonary (48.1%), extrapulmonary (22.64%) and disseminated (27.36%). Lymph node form was the most frequent (70.83%) extrapulmonary form of TB. The only single nucleotide polymorphism detected in the population was c.-392A>G. Genotypes observed were CYP3A4*1A/CYP3A4*1A (45.3%), CYP3A4*1A/CYP3A4*1B (40.6%) and CYP3A4*1B/ CYP3A4*1B (14.2%), revealing a different distribution with extrapulmonary TB cases (17.6% CYP3A4*1A/CYP3A4*1B and 23.5% CYP3A4*1B/CYP3A4*1B). The CYP3A4*1A allele was found to be associated with tobacco use. The CYP3A4*1B mutant allele occurred in 34% of patients. This study revealed that the CYP3A4 5'-upstream regulatory region was highly conserved with the exception of the -392 position. Genotype association with tobacco suggests that CYP3A4 may participate in tobacco metabolism. Genotype distribution inversion in extrapulmonary TB cases suggests that CYP3A4 may be involved in TB prognosis.

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Modification of Clinical Presentation of Prostate Tumors by a Novel Genetic Variant in CYP3A4

Abstract: We determined that a single base change in the 5' flanking region of the CYP3A4 gene was associated with higher clinical stage and grade in men with prostate tumors. Our results suggest that mutations in the CYP3A4 gene may influence prostate carcinogenesis.

Cited by 376 publications

References 13 publications

Sequence diversity and haplotype structure at the human CYP3A cluster

Sequence diversity and haplotype structure at the human CYP3A cluster

The role of candidate genetic polymorphisms in the etiology of prostate cancer

Unique CYP3A4 genetic variant in Brazilian tuberculosis patients with/without HIV

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