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CYP1A1 and CYP1B1 genetic polymorphisms, smoking and breast cancer risk in a Finnish Caucasian population

  • Epidemiology
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Abstract

We investigated the associations between two CYP1A1 polymorphisms (Ile462Val and Thr461Asn) and one CYP1B1 polymorphism (Leu432Val) and breast cancer risk. The study population consisted of 483 breast cancer patients and 482 healthy population controls, all of homogenous Finnish origin. No statistically significant overall associations were found between the CYP1A1 and CYP1B1 genotypes and breast cancer risk. However, a significant increase in the breast cancer risk was seen for women who had smoked 1–9 cigarettes/day and carried the CYP1B1 432Val allele; the OR was 2.6 (95% CI 1.07–6.46) for women carrying the Leu/Val genotype and 5.1 (95% CI 1.30–19.89, P for trend 0.005) for women with the Val/Val genotype compared to similarly smoking women homozygous for the 432Leu allele. Furthermore, when CYP1B1 genotypes were combined with the previously analyzed N-acetyl transferase (NAT2) genotypes, a significant increase in breast cancer risk was found among women who had at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype (OR 1.52; 95% CI 1.03–2.24) compared to women carrying a combination of CYP1B1 Leu/Leu and NAT2 rapid acetylator genotypes. This risk was seen to be confined to ever smokers; the OR was 2.46 (95% CI 1.11–5.45) for ever smokers carrying at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype compared to ever smokers with the CYP1B1 Leu/Leu and NAT2 rapid acetylator genotype combination. Our results suggest that the CYP1B1 polymorphism may be an important modifier of breast cancer risk in Finnish Caucasian women who have been exposed to tobacco smoke and/or carry the NAT2 slow acetylator genotype.

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Abbreviations

BMI:

Body mass index

CI:

Confidence interval

CYP:

Cytochrome P450

E2 :

17-β-estradiol

HRT:

Hormone replacement therapy

NAT2:

N-acetyl transferase

OC:

Oral contraceptive

OR:

Odds ratio

PAH:

Polycyclic aromatic hydrocarbon

PCB:

Polychlorinated biphenyl

PCR:

Polymerase chain reaction

RFLP:

Restriction fragment length polymorphism

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Acknowledgments

We thank our colleagues at the Kuopio Cancer Research Center and A.K. Lyytinen, R.,N., for data collection. This work was partly supported by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: ’’Food Quality and Safety” (Contract No 513943).

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Authors and Affiliations

  1. Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, Helsinki, 00250, Finland

    Pia Sillanpää, Liisa Heikinheimo, Harri Vainio, Katja Metsola & Ari Hirvonen

  2. Department of Oncology, Kuopio University Hospital, Kuopio, Finland

    Vesa Kataja

  3. Department of Surgery, Kuopio University Hospital, Kuopio, Finland

    Matti Eskelinen

  4. Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland

    Veli-Matti Kosma

  5. Department of Pathology and Forensic Medicine, Institute of Clinical Medicine, University of Kuopio, Kuopio, Finland

    Veli-Matti Kosma

  6. Department of Clinical Nutrition, School of Public Health and Clinical Nutrition, University of Kuopio, Kuopio, Finland

    Matti Uusitupa

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  1. Pia Sillanpää
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Correspondence to Ari Hirvonen.

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Sillanpää, P., Heikinheimo, L., Kataja, V. et al. CYP1A1 and CYP1B1 genetic polymorphisms, smoking and breast cancer risk in a Finnish Caucasian population . Breast Cancer Res Treat 104, 287–297 (2007). https://doi.org/10.1007/s10549-006-9414-6

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