New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men

Marja Marchesani (Corresponding Author), Anna Hakkarainen, Tomi-Pekka Tuomainen, Jari Kaikkonen, Eero Pukkala, Pekka Uimari, Eija Seppälä, Mika Matikainen, Olli Kallioniemi, Johanna Schleutker, Terho Lehtimäki, Jukka Salonen

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    Abstract

    Background: Human serum paraoxonase eliminates carcinogenic lipid-soluble radicals. Because expression of the main human paraoxonase gene PON1 varies widely in humans, certain PON1 polymorphisms might be associated with increased risks of cancer. We sought new functional mutations in PON1 and determined whether known or new PON1 mutations were associated with the risk for prostate cancer in a prospective, random, population-based sample of Finnish men and in a case–control study. Methods: Serum paraoxonase activity was measured in 835 healthy men in the Kuopio Ischaemic Heart Disease Risk Factor Study. PON1 mutations were identified by hierarchical phenotype-targeted sequencing in DNAs from the 100 men with the lowest paraoxonase activity in this cohort, and 1595 men in the cohort were genotyped for PON1 mutations by restriction fragment length polymorphism. Multivariable analysis was used to investigate the association of known and new PON1 mutations with incident prostate cancer in 1569 cancer-free men in the cohort followed for 9–14 years. In a case–control study of Finnish men, the association of prostate cancer with the PON1 mutation identified in the cohort study was investigated in 69 case patients with familial prostate cancer and 69 unmatched healthy control subjects. Results: We identified a new single-nucleotide PON1 polymorphism associated with decreased serum paraoxonase activity that caused an isoleucine→valine change at codon 102 in exon 4 (I102V). Of the 1569 men cancer-free at baseline, 56 (3.6%) were carriers of the I102V mutation. After adjusting for age and cholesterol-lowering medications, the relative risk for developing prostate cancer during follow-up was 6.3 (95% confidence interval [CI] = 2.1 to 19.2) among 102V allele carriers compared with noncarriers. Other PON1 alleles were not statistically significantly associated with prostate cancer. In the case–control study, patients with familial prostate cancer were more likely to be carriers of the PON1 I102V mutation than control subjects (odds ratio = 4.3, 95% CI = 0.9 to 21.5). Conclusion: The PON1 102V allele appears to be associated with an increased risk for prostate cancer.
    Original languageEnglish
    Pages (from-to)812-818
    Number of pages7
    JournalJournal of the National Cancer Institute
    Volume95
    Issue number11
    DOIs
    Publication statusPublished - 2003
    MoE publication typeA1 Journal article-refereed

    Fingerprint

    Aryldialkylphosphatase
    Prostatic Neoplasms
    Mutation
    Alleles
    Serum
    Confidence Intervals
    Neoplasms
    DNA Sequence Analysis
    Codon
    Restriction Fragment Length Polymorphisms
    Myocardial Ischemia
    Single Nucleotide Polymorphism
    Exons
    Healthy Volunteers
    Cohort Studies
    Odds Ratio
    Cholesterol
    Phenotype
    Lipids

    Cite this

    Marchesani, M., Hakkarainen, A., Tuomainen, T-P., Kaikkonen, J., Pukkala, E., Uimari, P., ... Salonen, J. (2003). New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men. Journal of the National Cancer Institute, 95(11), 812-818. https://doi.org/10.1093/jnci/95.11.812
    Marchesani, Marja ; Hakkarainen, Anna ; Tuomainen, Tomi-Pekka ; Kaikkonen, Jari ; Pukkala, Eero ; Uimari, Pekka ; Seppälä, Eija ; Matikainen, Mika ; Kallioniemi, Olli ; Schleutker, Johanna ; Lehtimäki, Terho ; Salonen, Jukka. / New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men. In: Journal of the National Cancer Institute. 2003 ; Vol. 95, No. 11. pp. 812-818.
    @article{4e0c94cf55bd4950a1d26ab1410d3598,
    title = "New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men",
    abstract = "Background: Human serum paraoxonase eliminates carcinogenic lipid-soluble radicals. Because expression of the main human paraoxonase gene PON1 varies widely in humans, certain PON1 polymorphisms might be associated with increased risks of cancer. We sought new functional mutations in PON1 and determined whether known or new PON1 mutations were associated with the risk for prostate cancer in a prospective, random, population-based sample of Finnish men and in a case–control study. Methods: Serum paraoxonase activity was measured in 835 healthy men in the Kuopio Ischaemic Heart Disease Risk Factor Study. PON1 mutations were identified by hierarchical phenotype-targeted sequencing in DNAs from the 100 men with the lowest paraoxonase activity in this cohort, and 1595 men in the cohort were genotyped for PON1 mutations by restriction fragment length polymorphism. Multivariable analysis was used to investigate the association of known and new PON1 mutations with incident prostate cancer in 1569 cancer-free men in the cohort followed for 9–14 years. In a case–control study of Finnish men, the association of prostate cancer with the PON1 mutation identified in the cohort study was investigated in 69 case patients with familial prostate cancer and 69 unmatched healthy control subjects. Results: We identified a new single-nucleotide PON1 polymorphism associated with decreased serum paraoxonase activity that caused an isoleucine→valine change at codon 102 in exon 4 (I102V). Of the 1569 men cancer-free at baseline, 56 (3.6{\%}) were carriers of the I102V mutation. After adjusting for age and cholesterol-lowering medications, the relative risk for developing prostate cancer during follow-up was 6.3 (95{\%} confidence interval [CI] = 2.1 to 19.2) among 102V allele carriers compared with noncarriers. Other PON1 alleles were not statistically significantly associated with prostate cancer. In the case–control study, patients with familial prostate cancer were more likely to be carriers of the PON1 I102V mutation than control subjects (odds ratio = 4.3, 95{\%} CI = 0.9 to 21.5). Conclusion: The PON1 102V allele appears to be associated with an increased risk for prostate cancer.",
    author = "Marja Marchesani and Anna Hakkarainen and Tomi-Pekka Tuomainen and Jari Kaikkonen and Eero Pukkala and Pekka Uimari and Eija Sepp{\"a}l{\"a} and Mika Matikainen and Olli Kallioniemi and Johanna Schleutker and Terho Lehtim{\"a}ki and Jukka Salonen",
    year = "2003",
    doi = "10.1093/jnci/95.11.812",
    language = "English",
    volume = "95",
    pages = "812--818",
    journal = "Journal of the National Cancer Institute",
    issn = "0027-8874",
    publisher = "Oxford University Press",
    number = "11",

    }

    Marchesani, M, Hakkarainen, A, Tuomainen, T-P, Kaikkonen, J, Pukkala, E, Uimari, P, Seppälä, E, Matikainen, M, Kallioniemi, O, Schleutker, J, Lehtimäki, T & Salonen, J 2003, 'New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men', Journal of the National Cancer Institute, vol. 95, no. 11, pp. 812-818. https://doi.org/10.1093/jnci/95.11.812

    New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men. / Marchesani, Marja (Corresponding Author); Hakkarainen, Anna; Tuomainen, Tomi-Pekka; Kaikkonen, Jari; Pukkala, Eero; Uimari, Pekka; Seppälä, Eija; Matikainen, Mika; Kallioniemi, Olli; Schleutker, Johanna; Lehtimäki, Terho; Salonen, Jukka.

    In: Journal of the National Cancer Institute, Vol. 95, No. 11, 2003, p. 812-818.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - New paraoxonase 1 polymorphism I102V and the risk of prostate cancer in Finnish men

    AU - Marchesani, Marja

    AU - Hakkarainen, Anna

    AU - Tuomainen, Tomi-Pekka

    AU - Kaikkonen, Jari

    AU - Pukkala, Eero

    AU - Uimari, Pekka

    AU - Seppälä, Eija

    AU - Matikainen, Mika

    AU - Kallioniemi, Olli

    AU - Schleutker, Johanna

    AU - Lehtimäki, Terho

    AU - Salonen, Jukka

    PY - 2003

    Y1 - 2003

    N2 - Background: Human serum paraoxonase eliminates carcinogenic lipid-soluble radicals. Because expression of the main human paraoxonase gene PON1 varies widely in humans, certain PON1 polymorphisms might be associated with increased risks of cancer. We sought new functional mutations in PON1 and determined whether known or new PON1 mutations were associated with the risk for prostate cancer in a prospective, random, population-based sample of Finnish men and in a case–control study. Methods: Serum paraoxonase activity was measured in 835 healthy men in the Kuopio Ischaemic Heart Disease Risk Factor Study. PON1 mutations were identified by hierarchical phenotype-targeted sequencing in DNAs from the 100 men with the lowest paraoxonase activity in this cohort, and 1595 men in the cohort were genotyped for PON1 mutations by restriction fragment length polymorphism. Multivariable analysis was used to investigate the association of known and new PON1 mutations with incident prostate cancer in 1569 cancer-free men in the cohort followed for 9–14 years. In a case–control study of Finnish men, the association of prostate cancer with the PON1 mutation identified in the cohort study was investigated in 69 case patients with familial prostate cancer and 69 unmatched healthy control subjects. Results: We identified a new single-nucleotide PON1 polymorphism associated with decreased serum paraoxonase activity that caused an isoleucine→valine change at codon 102 in exon 4 (I102V). Of the 1569 men cancer-free at baseline, 56 (3.6%) were carriers of the I102V mutation. After adjusting for age and cholesterol-lowering medications, the relative risk for developing prostate cancer during follow-up was 6.3 (95% confidence interval [CI] = 2.1 to 19.2) among 102V allele carriers compared with noncarriers. Other PON1 alleles were not statistically significantly associated with prostate cancer. In the case–control study, patients with familial prostate cancer were more likely to be carriers of the PON1 I102V mutation than control subjects (odds ratio = 4.3, 95% CI = 0.9 to 21.5). Conclusion: The PON1 102V allele appears to be associated with an increased risk for prostate cancer.

    AB - Background: Human serum paraoxonase eliminates carcinogenic lipid-soluble radicals. Because expression of the main human paraoxonase gene PON1 varies widely in humans, certain PON1 polymorphisms might be associated with increased risks of cancer. We sought new functional mutations in PON1 and determined whether known or new PON1 mutations were associated with the risk for prostate cancer in a prospective, random, population-based sample of Finnish men and in a case–control study. Methods: Serum paraoxonase activity was measured in 835 healthy men in the Kuopio Ischaemic Heart Disease Risk Factor Study. PON1 mutations were identified by hierarchical phenotype-targeted sequencing in DNAs from the 100 men with the lowest paraoxonase activity in this cohort, and 1595 men in the cohort were genotyped for PON1 mutations by restriction fragment length polymorphism. Multivariable analysis was used to investigate the association of known and new PON1 mutations with incident prostate cancer in 1569 cancer-free men in the cohort followed for 9–14 years. In a case–control study of Finnish men, the association of prostate cancer with the PON1 mutation identified in the cohort study was investigated in 69 case patients with familial prostate cancer and 69 unmatched healthy control subjects. Results: We identified a new single-nucleotide PON1 polymorphism associated with decreased serum paraoxonase activity that caused an isoleucine→valine change at codon 102 in exon 4 (I102V). Of the 1569 men cancer-free at baseline, 56 (3.6%) were carriers of the I102V mutation. After adjusting for age and cholesterol-lowering medications, the relative risk for developing prostate cancer during follow-up was 6.3 (95% confidence interval [CI] = 2.1 to 19.2) among 102V allele carriers compared with noncarriers. Other PON1 alleles were not statistically significantly associated with prostate cancer. In the case–control study, patients with familial prostate cancer were more likely to be carriers of the PON1 I102V mutation than control subjects (odds ratio = 4.3, 95% CI = 0.9 to 21.5). Conclusion: The PON1 102V allele appears to be associated with an increased risk for prostate cancer.

    U2 - 10.1093/jnci/95.11.812

    DO - 10.1093/jnci/95.11.812

    M3 - Article

    VL - 95

    SP - 812

    EP - 818

    JO - Journal of the National Cancer Institute

    JF - Journal of the National Cancer Institute

    SN - 0027-8874

    IS - 11

    ER -