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Organochlorines, p53 mutations in relation to breast cancer risk and survival. A Danish cohort-nested case-controls study

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Abstract

Epidemiological studies integrating genetic susceptibility with biological measurements of organochlorine exposure may provide new clues regarding these substances influence on breast cancer etiology. Initial attempts pursuing this avenue has dealt with polymorphisms in the carcinogen-metabolizing enzymes cytochrome P450 (CYPlAl). This study examined if mutations in the tumor suppressor gene p53 affected organochlorine exposure related breast cancer risk and survival. The material consisted of 162 breast cancer cases and 316 matched controls, who had participated, in the Copenhagen City Heart Study (CCHS) between 1976 and 1978. Cases diagnosed between study initiation and 1993 were identified by linkage to the Danish Cancer Registry. The case group served as a cohort in the survival analyses. Information on known and suspected breast cancer risk factors was obtained from CCHS, and the Danish Breast Cancer Cooperative Group provided information on tumor characteristics. Lipid adjusted serum concentrations of selected organochlorines were compared between cases and controls while stratifing by p53 mutation status. A non-significant increased risk of breast cancer was observed in the highest exposure level of dieldrin and polychlorinated biphenyls among women who developed a tumor with mutant p53 (odds ratio (OR) = 3.53, 95% confidence interval (CI) = 0.79–15.79 and OR = 3.00, 95% CI = 0.66–13.62). There was no clear difference in overall survival between breast cancer cases with 'wild-type' and mutant p53, although a significant dose-response relationship appeared for dieldrin exposure in tumors with 'wild-type' p53. These preliminary results suggest that p53 mutations may have a modifying effect on at least the breast cancer risk associated with exposures to organochlorines.

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Authors and Affiliations

  1. The Copenhagen Center for Prospective Population Studies, Denmark

    Annette Pernille Høyer

  2. Department of Clinical Genetics, Denmark

    Anne-Marie Gerdes

  3. Centre of Preventive Medicine, KAS Glostrup, Glostrup

    Torben Jørgensen

  4. Department of Pathology, the Copenhagen University Hospital, Rigshospitalet, Copenhagen

    Fritz Rank

  5. Department of Biostatistics, Aarhus University, Aarhus, Denmark

    Helle Bøggild Hartvig

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  1. Annette Pernille Høyer
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  2. Anne-Marie Gerdes
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  4. Fritz Rank
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  5. Helle Bøggild Hartvig
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Høyer, A.P., Gerdes, AM., Jørgensen, T. et al. Organochlorines, p53 mutations in relation to breast cancer risk and survival. A Danish cohort-nested case-controls study. Breast Cancer Res Treat 71, 59–65 (2002). https://doi.org/10.1023/A:1013340327099

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