Racial differences in CYP1A1 genotype and function

Taioli, Emanuela; Crofts, Frances; Trachman, Julie; Bayo, S; Toniolo, Paolo; Garte, Seymour

doi:10.1016/0378-4274(95)03318-1

Cited by 38 publications

(29 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that these polymorphisms are in linkage disequilibrium in Caucasians, but not in African Americans [13]. Additionally, a third polymorphism in CYP1A1 that is unique to African Americans has also been identified.…”

Section: Cyp1a1mentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found in tobacco smoke. To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk, a populationbased case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 383 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 449 age, race and sexmatched controls ascertained through random digit dialing. Genotype frequencies varied significantly by race for CYP1A1 exon 7 Ile 462 Val and CYP1B1 Leu 432 Val genotypes, so all analyses were stratified by race. No association was seen between lung cancer risk and polymorphisms in CYP1A1 MspI or CYP1B1 Leu 432 Val for Caucasians or African Americans, after adjusting for age at diagnosis, sex, pack years of smoking and family history of lung cancer. In Caucasians, those with the Ile/Val genotype at CYP1A1 exon 7 locus were at decreased risk of having lung cancer compared to those with the Ile/Ile genotype, after adjusting for age at diagnosis, sex, pack years of smoking and family history of cancer (OR=0.41 95% CI 0.19-0.90). These results were not replicated among the African American population, nor were they modified by amount of smoking.

show abstract

Section: Cyp1a1mentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

show abstract

“…We hypothesized that endometrial cancer incidence would be relatively lower in women with genotypes that might be associated with inferred higher estrogen 2-hydroxylation and lower 4-hydroxylation and higher among women with an inferred impaired ability to convert the putative high-risk 4-hydroxylated metabolites to less harmful compounds and the 2-hydroxylated metabolites to compounds thought to be protective (see Table 1). Specifically, based on experimental evidence indicating that the CYP1A1 m1 and m2 variants might be associated with higher enzyme activity and/or inducibility (24)(25)(26)(27)(28) and therefore possibly increased 2-OH estrogen formation, we hypothesized that they might be associated with a decreased (10) 13 (3) Only estrogen + progestin 121 (33) 176 (42) Unopposed estrogen and estrogen + progestin 46 (13) 41 (10) Unopposed progestin and estrogen + progestin…”

Section: Discussionmentioning

confidence: 99%

“…For CYP1A1, these include CYP1A1 m1 (or MspI, T6235C), which has been observed to be associated with a high inducibility phenotype in several (24)(25)(26)(27)(28) but not all (29-31) studies; CYP1A1 m2 (exon 7, A4889G, Ile 462 Val), which may be associated with increased enzyme activity and inducibility (27,28,(32)(33)(34), although some studies did not observe this (26,(35)(36)(37) Met substitution due to a G-to-A transition in exon 4 of the COMT gene results in a heat-labile enzyme that is 4-to 5-fold less effective at methylating catechol substrates in vitro (50). The Met allele has been reported to result in 2-to 3-fold lower levels of methoxyestrogen metabolite formation in one (51), but not another (52), study.…”

Section: Introductionmentioning

confidence: 99%

Genetic Factors in Catechol Estrogen Metabolism in Relation to the Risk of Endometrial Cancer

Doherty

Weiss

Freeman

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

2-Hydroxylated metabolites of estrogen have been shown to have antiangiogenic effects and inhibit tumor cell proliferation, whereas 4-hydroxylated metabolites have been implicated in carcinogenesis. We examined whether polymorphisms in certain genes involved in estrogen metabolism are associated with endometrial cancer risk in a populationbased case-control study with 371 cases and 420 controls. Based on previously published genotype-phenotype correlation studies, we defined variant alleles thought to increase estrogen 2-hydroxylation as presumptively low-risk (CYP1A1 m1 T6235C and m2 Ile 462 Val) and those thought to increase estrogen 4-hydroxylation as high-risk (CYP1A1 m4 Thr 461 Asn, CYP1A2 A734C, and CYP1B1 Leu 432 Val). Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression. Carrying at least one CYP1A1 m1 or m2 variant allele was associated with a decreased risk of endometrial cancer [ORs (95% CIs), 0.64 (0.44-0.93) and 0.54 (0.30-0.99), respectively]. No strong alteration in risk was observed among women with any of the putative high-risk alleles. When CYP1A1, CYP1A2, and CYP1B1 genotypes were combined and ranked by the number of putative low-risk genotypes carried, women with four or five low-risk genotypes had a reduced risk of endometrial cancer (OR, 0.29; 95% CI, 0.15-0.56) compared with women with one or none. No appreciable alteration in risk was observed among women carrying two or three low-risk genotypes. Some of our findings are consistent with the hypothesis that increased estrogen 2-hydroxylation is associated with decreased endometrial cancer risk, but replication of these results is required before any firm conclusions can be reached.

show abstract

“…These proteins are polymorphic and some variants are more or less efficient for activation or detoxification ( Table 2). The prevalence of specific variants may further vary by ethnicity (Table 2), and one report has found an increased risk of breast cancer among African-American women who harbor an MsPI variant in CYPIAI (13). Additional risk may arise when specific exposures are experienced by individuals with an at-risk genotype.…”

Section: Mechanistic Considerationsmentioning

confidence: 99%

Breast cancer risk and environmental exposures.

Wolff

Weston

1997

Environ Health Perspect

View full text Add to dashboard Cite

Although environmental contaminants have potential to affect breast cancer risk, explicit environmental links to this disease are limited. The most well-defined environmental risk factors are radiation exposure and alcohol ingestion. Diet is clearly related to the increased incidence of breast cancer in developed countries, but its precise role is not yet established. Recent studies have implicated exposure to organochlorines including DDT as a risk factor for breast cancer in the United States, Finland, Mexico, and Canada. Other investigations have discovered associations between breast cancer risk and exposures to chemical emissions and some occupational exposures. Several points must be considered in evaluating the relationship of environmental exposure to breast cancer. Among these considerations are the mechanism of tumorigenesis, timing of environmental exposure, and genetic modulation of exposure. Epidemiologic and ecologic investigations must take into account the very complex etiology of breast cancer and the knowledge that tumorigenesis can arise from different mechanisms. Thus crucial exposures as well as reproductive events related to breast cancer may occur years before a tumor is evident. Moreover, environmental contaminants may alter reproductive development, directly or indirectly, and thereby effect the course of tumorigenesis. Such alterations include change in gender, change in onset of puberty, and inhibition or promotion of tumor formation. Timing of exposure is therefore important with respect to mechanism and susceptibility. Finally, genetic polymorphisms exist in genes that govern capacity to metabolize environmental contaminants. Higher risk may occur among persons whose enzymes either are more active in the production of procarcinogens or fail to detoxify carcinogenic intermediates formed from chemicals in the environment.

show abstract

Racial differences in CYP1A1 genotype and function

Cited by 38 publications

References 10 publications

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

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

Genetic Factors in Catechol Estrogen Metabolism in Relation to the Risk of Endometrial Cancer

Breast cancer risk and environmental exposures.

Contact Info

Product

Resources

About