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Cumulative genetic defects in carcinogen metabolism may increase breast cancer risk (The Netherlands)

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Abstract

Variants in the metabolic genes NAT1, NAT2, GSTM1 or GSTT1, may cause differences in individual detoxifying capacity of possible carcinogens. We examined the cumulative effect of putative at risk genotypes on breast cancer risk and we examined the extent to which these polymorphisms modify the association between smoking and breast cancer. A case cohort study was conducted in the DOM cohort with 676 breast cancer cases and a random sample of 669 individuals. No effect of the NAT1, NAT2 or GSTM1 genotypes on breast cancer risk was observed. However, women with GSTT1 null genotype had a 30% increased breast cancer risk compared to women with GSTT1 present (RR = 1.30 (95% confidence interval (CI) 1.04–1.64)). Smoking did not influence breast cancer risk nor did genetic variations in NAT1, NAT2 or GSTM1 in combination with smoking. Compared to women who never smoked with GSTT1 present, women with GSTT1 null genotype and who formerly smoked showed an increased breast cancer risk (RR = 2.55 (95% CI 1.10–5.90)), but current smokers who smoked 20 cigarettes or more per day did not (RR = 1.06 (95% CI 0.51–2.18)). Increasing numbers of putative at risk genotypes increased breast cancer risk in a dose dependent manner (p for trend 0.01). The risk was more than doubled in women with all four risk genotypes, RR = 2.45 (95% CI 1.24–4.86), compared to women with zero putative at risk genotypes. In conclusion, the results of this study suggest that presence of three or more putative at risk genotypes increases breast cancer risk.

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Abbreviations

BMI:

body mass index

CI:

confidence interval

DOM:

diagnostic study on breast cancer

GST:

glutathione S-transferase

IRR:

incidence rate ratio

NAT:

N-acetyltransferase

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Author notes

  1. Olga L. van der Hel

    Present address: International Agency for Research on Cancer, 69008, Lyon, France

Authors and Affiliations

  1. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508, GA, Utrecht, The Netherlands

    Olga L. van der Hel, Carla H. van Gils, Diederick E. Grobbee & Petra H. M. Peeters

  2. Department of Chronic Diseases Epidemiology, National Insitute of Public Health and the Environment, PO Box 1, 3720, BA, Bilthoven, The Netherlands

    H. Bas Bueno-de-Mesquita

  3. Division of Clinical Chemistry, University Medical Center Utrecht, PO Box 85500, 3508, GA, Utrecht, The Netherlands

    Mark Roest & Barbara Slothouber

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  1. Olga L. van der Hel
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  2. H. Bas Bueno-de-Mesquita
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Corresponding author

Correspondence to Petra H. M. Peeters.

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Hel, O.L.v.d., Bueno-de-Mesquita, H.B., Gils, C.H.v. et al. Cumulative genetic defects in carcinogen metabolism may increase breast cancer risk (The Netherlands). Cancer Causes Control 16, 675–681 (2005). https://doi.org/10.1007/s10552-005-1227-0

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  • DOI: https://doi.org/10.1007/s10552-005-1227-0

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