The effect of the <i>CYP1A2 *1F</i> mutation on CYP1A2 inducibility in pregnant women

Nordmark, Anna; Lundgren, Stefan; Ask, Birgitta; Granath, Fredrik; Rane, Anders

doi:10.1046/j.1365-2125.2002.01673.x

Cited by 50 publications

(29 citation statements)

References 39 publications

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“…In our case-only study, f50% of the patients carried the CYP1A2*1F A/A genotype, which is consistent with the frequencies reported in other studies (10,32), and the distribution of the genotypes was in Hardy-Weinberg equilibrium. CYP1A2*1F is located in intron 1 of the CYP1A2 gene.…”

Section: Discussionsupporting

confidence: 80%

Coffee Consumption and CYP1A21F* Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status

Bågeman¹,

Ingvar²,

Rose³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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CYP1A2 plays a key role in the metabolism of both estrogen and coffee. Women with higher coffee intake and the CYP1A2*1F A/A genotype have a ratio of high 2-hydroxyestrone (2-OHE1) to 16A-OHE1. 2-OHE1 is a weak estrogen and may even block the estrogen receptor (ER), whereas 16A-OHE1 is procarcinogenic. We hypothesized that moderate to high coffee consumption (z2 cups per day) combined with the CYP1A2*1F A/A genotype would be associated with a later age at diagnosis and a greater proportion of ER-negative (ERÀ) tumors among patients with breast cancer. We genotyped 458 patients with breast cancer (age, 25-99 years) in Lund, Sweden, for CYP1A2*1F. Information on lifestyle factors and tumor characteristics were obtained from preoperative questionnaires and pathology reports. Among patients with CYP1A2*1F A/A (51.3%), moderate to high consumption was associated with a later age at diagnosis compared with low coffee consumption (59.8 versus 52.6 years, P = 0.0004). These patients were also more likely to have ERÀ tumors than patients with low consumption (14.7% versus 0%, P = 0.018). Coffee was not associated with ER status or age at diagnosis in patients with at least one C allele. Age at diagnosis was not associated with ER status in patients with CYP1A2*1F A/A, but younger patients (<50 years) with at least one C allele were more likely to have ERÀ tumors compared with older patients (odds ratio, 4.2; 95% confidence interval, 1.9-9.3; P = 0.0002). These findings raise the hypothesis that coffee slows the growth of ER-positive tumors in patients with CYP1A2*1F A/A and may have implications for breast cancer if confirmed. (Cancer Epidemiol Biomarkers Prev 2008;17(4):895 -901)

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Section: Discussionsupporting

confidence: 80%

Coffee Consumption and CYP1A21F* Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status

Bågeman¹,

Ingvar²,

Rose³

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The CYP1A2 À163A allele has more often been associated with increased enzymatic activity, which would lead to higher catechol estrogen formation (32)(33)(34). The association we observed is consistent with a recently conducted case-control study of TGCC (35).…”

Section: Discussionsupporting

confidence: 79%

Risk of Testicular Germ Cell Cancer in Relation to Variation in Maternal and Offspring CytochromeP450 Genes Involved in Catechol Estrogen Metabolism

Starr

Chen

Doody

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The incidence of testicular germ cell carcinoma (TGCC) is highest among men ages 20 to 44 years. Exposure to relatively high circulating maternal estrogen levels during pregnancy has long been suspected as being a risk factor for TGCC. Catechol (hydroxylated) estrogens have carcinogenic potential, thought to arise from reactive catechol intermediates with enhanced capability of forming mutation-inducing DNA adducts. Polymorphisms in maternal or offspring genes encoding estrogenmetabolizing enzymes may influence prenatal catechol estrogen levels and could therefore be biomarkers of TGCC risk. We conducted a population-based, case-parent triad study to evaluate TGCC risk in relation to maternal and/or offspring polymorphisms in CYP1A2, CYP1B1, CYP3A4, and CYP3A5. We identified 18-to 44-year-old men diagnosed with invasive TGCC from 1999 to 2004 through a population-based cancer registry in Washington State and recruited cases and their parents (110 case-parent triads, 50 case-parent dyads). Maternal or offspring carriage of CYP1A2 À163A was associated with reduced risk of TGCC [maternal heterozygote relative risk (RR), 0.6; 95% confidence interval (95% CI), 0.2-1.7; offspring heterozygote RR, 0.7; 95% CI, 0.3-1.5)]. Maternal CYP1B1 48Gly homozygosity was associated with a 2.7-fold increased risk of TGCC (95% CI, 0.9-7.9), with little evidence that Leu 432 Val or Asn 453Ser genotypes were related to risk. Men were also at increased risk of TGCC if they carried the CYP3A4 À392G (RR, 7.0; 95% CI, 1.6-31) or CYP3A5 6986G (RR, 2.4; 95% CI, 1.1-5.6) alleles. These results support the hypothesis that maternal and/or offspring catechol estrogen activity may influence sons' risk of TGCC. (Cancer Epidemiol Biomarkers Prev 2005;14(9): 2183-90)

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“…In this study, approximately 50% of the women carried the CYP1A2*1F A/A genotype, which is consistent with reported frequencies (Sachse et al, 1999;Nordmark et al, 2002). CYP1A2*1F is located in intron 1 and may not directly be associated with enzyme activity, but is rather linked to other polymorphisms with regulatory properties (Sachse et al, 1999).…”

Section: Discussionsupporting

confidence: 78%

Coffee intake and CYP1A2*1F genotype predict breast volume in young women: implications for breast cancer

et al. 2008

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As breast volume may be associated with heart cancer risk, we studied the relationship between breast volume, CYP1A2*1F and coffee intake. Among healthy premenopausal non-hormone users, 3 þ cups per day was associated with lower volume only in C-allele carriers (P interaction ¼ 0.02), which is consistent with reports that coffee protects only C-allele carriers against breast cancer. A recent study reported that coffee reduced the risk of breast cancer in BRCA1 carriers with the CYP1A2*1F C-allele but not in those with the CYP1A2*1F A/A genotype (Kotsopoulos et al, 2007). Another study found significantly lower coffee consumption in sporadic breast cancer cases with at least one C-allele compared with the A/A genotype (Bågeman et al, 2008) in spite of the fact that coffee consumption is similar across CYP1A2*1F genotypes in the general population (Cornelis et al, 2006). Some studies (Vatten et al, 1990;Baker et al, 2006;Nkondjock et al, 2006;Ganmaa et al, 2008), but not all (Rosenberg et al, 1985;Vatten et al, 1990;McLaughlin et al, 1992;Stensvold and Jacobsen, 1994;Michels et al, 2002), have reported that moderate-to-high coffee consumption protects against breast cancer, though a mechanism is unknown. None of these studies took CYP1A2*1F into account.Coffee is metabolised by the CYP1A2 enzyme, which also plays a key role in oestrogen metabolism (Le Marchand et al, 1997;Lee et al, 2003). Coffee contains not only caffeine but also phytooestrogens that can interact with and even block the oestrogen receptor (Magee and Rowland, 2004). Women with high coffee intake and the highly inducible CYP1A2*1F A/A genotype (Sachse et al, 1999) have a high 2-hydroxyoestrone (2-OHE1) to 16a-OHE1 ratio (Jernström et al, 2003;Bradlow et al, 2006;Klug et al, 2006). 2-Hydroxyoestrone is a weak oestrogen (Schneider et al, 1984), whereas 16a-OHE1 is procarcinogenic (Telang et al, 1992). In line with this, we found that breast volume in breast cancer patients was significantly higher in women with a lower 2-OHE to 16a-OHE1 ratio . Coffee also affects testosterone and SHBG levels (Ferrini and Barrett-Connor, 1996;Nagata et al, 1998). Although hormonal regulation of breast tissue has been extensively studied, little is known about hormones, genes, diet influence, density, size and diseases of the breast.Mammographic density is a strong risk factor for breast cancer (Boyd et al, 2005), the risk increasing with larger percentage density. The non-inducible CYP1A2*1F C-allele was associated with the percent density in normal-weight postmenopausal women not using hormone therapy (Takata et al, 2007). CYP1A2 enzyme activity has also been associated with density (Hong et al, 2004), and coffee induces CYP1A2 enzyme activity (Djordjevic et al, 2007). There is no direct correlation between breast density and size after adjustment for waist-to-hip ratio and BMI (Beijerinck et al, 1995). However, a larger breast size has been associated with increased breast cancer risk (Kato et al, 1995), especially in lean women (Kusano et al, 2006) or in women wi...

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The effect of the CYP1A2 1F* mutation on CYP1A2 inducibility in pregnant women

Cited by 50 publications

References 39 publications

Coffee Consumption and CYP1A21F* Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status

Coffee Consumption and CYP1A21F* Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status

Risk of Testicular Germ Cell Cancer in Relation to Variation in Maternal and Offspring CytochromeP450 Genes Involved in Catechol Estrogen Metabolism

Coffee intake and CYP1A2*1F genotype predict breast volume in young women: implications for breast cancer

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The effect of the CYP1A2 *1F mutation on CYP1A2 inducibility in pregnant women

Cited by 50 publications

References 39 publications

Coffee Consumption and CYP1A2*1F Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status

Coffee Consumption and CYP1A2*1F Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status

Risk of Testicular Germ Cell Cancer in Relation to Variation in Maternal and Offspring CytochromeP450 Genes Involved in Catechol Estrogen Metabolism

Coffee intake and CYP1A2*1F genotype predict breast volume in young women: implications for breast cancer

Contact Info

Product

Resources

About

The effect of the CYP1A2 1F* mutation on CYP1A2 inducibility in pregnant women

Coffee Consumption and CYP1A21F* Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status

Coffee Consumption and CYP1A21F* Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status