Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP

Bjørn A. Nexø, Ulla Vogel, Anja Olsen, Mette Nygaard, Zuzanna Bukowy, Eszter Rockenbauer, Xiuqing Zhang, Cemile koca, Mette Mains, Bettina Hansen, Anne Hedemand, anette Kjeldgaard, Magdalena L. Laska, Ole Raaschou-Nielsen, Søren Cold, Kim Overvad, Anne Tjønneland, Lars Bolund, Anders D. Børglum

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Background

    Previous results have suggested an association of the region of 19q13.3 with several forms of cancer. In the present study, we investigated 27 public markers within a previously identified 69 kb stretch of chromosome 19q for association with breast cancer by using linkage disequilibrium mapping. The study groups included 434 postmenopausal breast cancer cases and an identical number of individually matched controls.

    Methods and Results

    Studying one marker at a time, we found a region spanning the gene RAI (alias PPP1R13L or iASPP) and the 5' portion of XPD to be associated with this cancer. The region corresponds to a haplotype block, in which there seems to be very limited recombination in the Danish population. Studying combinations of markers, we found that two to four neighboring markers gave the most consistent and strongest result. The haplotypes with strongest association with cancers were located in the gene RAI and just 3' to the gene. Coinciding peaks were seen in the region of RAI in groups of women of different age.

    In a follow-up to these results we sequenced 10 cases and 10 controls in a 44 kb region spanning the peaks of association. This revealed 106 polymorphisms, many of which were not in the public databases. We tested an additional 44 of these for association with disease and found a new tandem repeat marker, called RAI-3'd1, located downstream of the transcribed region of RAI, which was more strongly associated with breast cancer than any other marker we have tested (RR = 2.44 (1.41-4.23, p = 0.0008, all cases; RR = 6.29 (1.49-26.6), p = 0.01, cases up to 55 years of age).

    Conclusion

    We expect the marker RAI-3'd1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer

    OriginalsprogEngelsk
    TidsskriftBMC Medical Genetics
    Vol/bind9
    ISSN1471-2350
    DOI
    StatusUdgivet - 2008

    Bibliografisk note

    Paper id:: 56

    Citer dette

    Nexø, B. A., Vogel, U., Olsen, A., Nygaard, M., Bukowy, Z., Rockenbauer, E., ... Børglum, A. D. (2008). Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP. BMC Medical Genetics, 9. https://doi.org/10.1186/1471-2350-9-56
    Nexø, Bjørn A. ; Vogel, Ulla ; Olsen, Anja ; Nygaard, Mette ; Bukowy, Zuzanna ; Rockenbauer, Eszter ; Zhang, Xiuqing ; koca, Cemile ; Mains, Mette ; Hansen, Bettina ; Hedemand, Anne ; Kjeldgaard, anette ; Laska, Magdalena L. ; Raaschou-Nielsen, Ole ; Cold, Søren ; Overvad, Kim ; Tjønneland, Anne ; Bolund, Lars ; Børglum, Anders D. / Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP. I: BMC Medical Genetics. 2008 ; Bind 9.
    @article{2e22f390dd6911dd87fb000ea68e967b,
    title = "Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP",
    abstract = "BackgroundPrevious results have suggested an association of the region of 19q13.3 with several forms of cancer. In the present study, we investigated 27 public markers within a previously identified 69 kb stretch of chromosome 19q for association with breast cancer by using linkage disequilibrium mapping. The study groups included 434 postmenopausal breast cancer cases and an identical number of individually matched controls.Methods and ResultsStudying one marker at a time, we found a region spanning the gene RAI (alias PPP1R13L or iASPP) and the 5' portion of XPD to be associated with this cancer. The region corresponds to a haplotype block, in which there seems to be very limited recombination in the Danish population. Studying combinations of markers, we found that two to four neighboring markers gave the most consistent and strongest result. The haplotypes with strongest association with cancers were located in the gene RAI and just 3' to the gene. Coinciding peaks were seen in the region of RAI in groups of women of different age.In a follow-up to these results we sequenced 10 cases and 10 controls in a 44 kb region spanning the peaks of association. This revealed 106 polymorphisms, many of which were not in the public databases. We tested an additional 44 of these for association with disease and found a new tandem repeat marker, called RAI-3'd1, located downstream of the transcribed region of RAI, which was more strongly associated with breast cancer than any other marker we have tested (RR = 2.44 (1.41-4.23, p = 0.0008, all cases; RR = 6.29 (1.49-26.6), p = 0.01, cases up to 55 years of age).ConclusionWe expect the marker RAI-3'd1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer",
    author = "Nex{\o}, {Bj{\o}rn A.} and Ulla Vogel and Anja Olsen and Mette Nygaard and Zuzanna Bukowy and Eszter Rockenbauer and Xiuqing Zhang and Cemile koca and Mette Mains and Bettina Hansen and Anne Hedemand and anette Kjeldgaard and Laska, {Magdalena L.} and Ole Raaschou-Nielsen and S{\o}ren Cold and Kim Overvad and Anne Tj{\o}nneland and Lars Bolund and B{\o}rglum, {Anders D.}",
    note = "Paper id:: 56",
    year = "2008",
    doi = "10.1186/1471-2350-9-56",
    language = "English",
    volume = "9",
    journal = "B M C Medical Genetics",
    issn = "1471-2350",
    publisher = "BioMed Central Ltd.",

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    Nexø, BA, Vogel, U, Olsen, A, Nygaard, M, Bukowy, Z, Rockenbauer, E, Zhang, X, koca, C, Mains, M, Hansen, B, Hedemand, A, Kjeldgaard, A, Laska, ML, Raaschou-Nielsen, O, Cold, S, Overvad, K, Tjønneland, A, Bolund, L & Børglum, AD 2008, 'Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP', BMC Medical Genetics, bind 9. https://doi.org/10.1186/1471-2350-9-56

    Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP. / Nexø, Bjørn A.; Vogel, Ulla; Olsen, Anja; Nygaard, Mette; Bukowy, Zuzanna; Rockenbauer, Eszter; Zhang, Xiuqing; koca, Cemile; Mains, Mette; Hansen, Bettina; Hedemand, Anne; Kjeldgaard, anette; Laska, Magdalena L.; Raaschou-Nielsen, Ole; Cold, Søren; Overvad, Kim; Tjønneland, Anne; Bolund, Lars; Børglum, Anders D.

    I: BMC Medical Genetics, Bind 9, 2008.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP

    AU - Nexø, Bjørn A.

    AU - Vogel, Ulla

    AU - Olsen, Anja

    AU - Nygaard, Mette

    AU - Bukowy, Zuzanna

    AU - Rockenbauer, Eszter

    AU - Zhang, Xiuqing

    AU - koca, Cemile

    AU - Mains, Mette

    AU - Hansen, Bettina

    AU - Hedemand, Anne

    AU - Kjeldgaard, anette

    AU - Laska, Magdalena L.

    AU - Raaschou-Nielsen, Ole

    AU - Cold, Søren

    AU - Overvad, Kim

    AU - Tjønneland, Anne

    AU - Bolund, Lars

    AU - Børglum, Anders D.

    N1 - Paper id:: 56

    PY - 2008

    Y1 - 2008

    N2 - BackgroundPrevious results have suggested an association of the region of 19q13.3 with several forms of cancer. In the present study, we investigated 27 public markers within a previously identified 69 kb stretch of chromosome 19q for association with breast cancer by using linkage disequilibrium mapping. The study groups included 434 postmenopausal breast cancer cases and an identical number of individually matched controls.Methods and ResultsStudying one marker at a time, we found a region spanning the gene RAI (alias PPP1R13L or iASPP) and the 5' portion of XPD to be associated with this cancer. The region corresponds to a haplotype block, in which there seems to be very limited recombination in the Danish population. Studying combinations of markers, we found that two to four neighboring markers gave the most consistent and strongest result. The haplotypes with strongest association with cancers were located in the gene RAI and just 3' to the gene. Coinciding peaks were seen in the region of RAI in groups of women of different age.In a follow-up to these results we sequenced 10 cases and 10 controls in a 44 kb region spanning the peaks of association. This revealed 106 polymorphisms, many of which were not in the public databases. We tested an additional 44 of these for association with disease and found a new tandem repeat marker, called RAI-3'd1, located downstream of the transcribed region of RAI, which was more strongly associated with breast cancer than any other marker we have tested (RR = 2.44 (1.41-4.23, p = 0.0008, all cases; RR = 6.29 (1.49-26.6), p = 0.01, cases up to 55 years of age).ConclusionWe expect the marker RAI-3'd1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer

    AB - BackgroundPrevious results have suggested an association of the region of 19q13.3 with several forms of cancer. In the present study, we investigated 27 public markers within a previously identified 69 kb stretch of chromosome 19q for association with breast cancer by using linkage disequilibrium mapping. The study groups included 434 postmenopausal breast cancer cases and an identical number of individually matched controls.Methods and ResultsStudying one marker at a time, we found a region spanning the gene RAI (alias PPP1R13L or iASPP) and the 5' portion of XPD to be associated with this cancer. The region corresponds to a haplotype block, in which there seems to be very limited recombination in the Danish population. Studying combinations of markers, we found that two to four neighboring markers gave the most consistent and strongest result. The haplotypes with strongest association with cancers were located in the gene RAI and just 3' to the gene. Coinciding peaks were seen in the region of RAI in groups of women of different age.In a follow-up to these results we sequenced 10 cases and 10 controls in a 44 kb region spanning the peaks of association. This revealed 106 polymorphisms, many of which were not in the public databases. We tested an additional 44 of these for association with disease and found a new tandem repeat marker, called RAI-3'd1, located downstream of the transcribed region of RAI, which was more strongly associated with breast cancer than any other marker we have tested (RR = 2.44 (1.41-4.23, p = 0.0008, all cases; RR = 6.29 (1.49-26.6), p = 0.01, cases up to 55 years of age).ConclusionWe expect the marker RAI-3'd1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer

    U2 - 10.1186/1471-2350-9-56

    DO - 10.1186/1471-2350-9-56

    M3 - Journal article

    VL - 9

    JO - B M C Medical Genetics

    JF - B M C Medical Genetics

    SN - 1471-2350

    ER -