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A population-based case-control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer.

Abstract

XRCC1 (X-ray repair cross-complementing group 1) is a base excision repair protein that plays a central role in the repair of DNA base damage and strand breaks. A common polymorphism (Arg-->Gln) at codon 399 of the XRCC1 gene has been previously linked to functional changes of the gene product and risk of cancers. We evaluated the association between XRCC1 Arg399Gln polymorphism and breast cancer risk in the population-based Shanghai Breast Cancer Study involving 1088 cancer patients and 1182 community controls. Genomic DNA from peripheral blood was used in genotyping assays, and exposure information and anthropometrics were collected through in-person interview. Plasma estrogen and sex hormone-binding globulin (SHBG) levels were measured for 190 postmenopausal breast cancer patients who had donated a pretreatment blood sample and 407 postmenopausal controls. Conditional logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusting potential confounders. Approximately 27% of controls carried the variant allele (Gln), and cases and controls had a similar distribution for both allele type and genotype of this polymorphism. We found that 7.8% of cases and 6.3% of controls were homozygous for the variant allele, resulting in an OR of 1.20 (95% CI, 0.85-1.69). The OR was slightly higher among younger women [<45 years of age (OR, 1.39; 95% CI, 0.82-2.36)] than older women [> or = 45 years of age (OR, 1.07; 95% CI, 0.68-1.67)], but neither OR was statistically significant. No modifying effect of major breast cancer risk factors, including years of menstruation, body mass index, waist:hip ratio, and blood estrogen levels, was noted. Homozygosity for the variant Gln allele was associated with an elevated risk of postmenopausal breast cancer among subjects with a higher blood level of SHBG (OR, 3.27; 95% CI, 1.16-9.20) and a reduced risk among those with a lower level of SHBG (OR, 0.60; 95% CI, 0.18-1.97). The overall results of the study suggest that Arg399Gln polymorphism of the XRCC1 gene alone may not play a substantial role in the risk of breast cancer among Chinese women.

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  • Authors+Show Affiliations

    ,

    Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-8300, USA. Xaio-Ou.Shu@mail.vanderbilt.edu

    , , , ,

    Source

    MeSH

    Adult
    Age Distribution
    Aged
    Alleles
    Breast Neoplasms
    Case-Control Studies
    China
    Confidence Intervals
    DNA Repair
    DNA-Binding Proteins
    Female
    Gene Expression Regulation, Neoplastic
    Genetic Predisposition to Disease
    Humans
    Incidence
    Logistic Models
    Middle Aged
    Odds Ratio
    Polymerase Chain Reaction
    Polymorphism, Genetic
    Population Surveillance
    Probability
    Prognosis
    Reference Values
    Risk Assessment
    Sensitivity and Specificity
    Survival Analysis
    X-ray Repair Cross Complementing Protein 1

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    14693738

    Citation

    Shu, Xiao-Ou, et al. "A Population-based Case-control Study of the Arg399Gln Polymorphism in DNA Repair Gene XRCC1 and Risk of Breast Cancer." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 12, no. 12, 2003, pp. 1462-7.
    Shu XO, Cai Q, Gao YT, et al. A population-based case-control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2003;12(12):1462-7.
    Shu, X. O., Cai, Q., Gao, Y. T., Wen, W., Jin, F., & Zheng, W. (2003). A population-based case-control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 12(12), pp. 1462-7.
    Shu XO, et al. A Population-based Case-control Study of the Arg399Gln Polymorphism in DNA Repair Gene XRCC1 and Risk of Breast Cancer. Cancer Epidemiol Biomarkers Prev. 2003;12(12):1462-7. PubMed PMID: 14693738.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - A population-based case-control study of the Arg399Gln polymorphism in DNA repair gene XRCC1 and risk of breast cancer. AU - Shu,Xiao-Ou, AU - Cai,Qiuyin, AU - Gao,Yu-Tang, AU - Wen,Wanqing, AU - Jin,Fan, AU - Zheng,Wei, PY - 2003/12/25/pubmed PY - 2004/4/24/medline PY - 2003/12/25/entrez SP - 1462 EP - 7 JF - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JO - Cancer Epidemiol. Biomarkers Prev. VL - 12 IS - 12 N2 - XRCC1 (X-ray repair cross-complementing group 1) is a base excision repair protein that plays a central role in the repair of DNA base damage and strand breaks. A common polymorphism (Arg-->Gln) at codon 399 of the XRCC1 gene has been previously linked to functional changes of the gene product and risk of cancers. We evaluated the association between XRCC1 Arg399Gln polymorphism and breast cancer risk in the population-based Shanghai Breast Cancer Study involving 1088 cancer patients and 1182 community controls. Genomic DNA from peripheral blood was used in genotyping assays, and exposure information and anthropometrics were collected through in-person interview. Plasma estrogen and sex hormone-binding globulin (SHBG) levels were measured for 190 postmenopausal breast cancer patients who had donated a pretreatment blood sample and 407 postmenopausal controls. Conditional logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusting potential confounders. Approximately 27% of controls carried the variant allele (Gln), and cases and controls had a similar distribution for both allele type and genotype of this polymorphism. We found that 7.8% of cases and 6.3% of controls were homozygous for the variant allele, resulting in an OR of 1.20 (95% CI, 0.85-1.69). The OR was slightly higher among younger women [<45 years of age (OR, 1.39; 95% CI, 0.82-2.36)] than older women [> or = 45 years of age (OR, 1.07; 95% CI, 0.68-1.67)], but neither OR was statistically significant. No modifying effect of major breast cancer risk factors, including years of menstruation, body mass index, waist:hip ratio, and blood estrogen levels, was noted. Homozygosity for the variant Gln allele was associated with an elevated risk of postmenopausal breast cancer among subjects with a higher blood level of SHBG (OR, 3.27; 95% CI, 1.16-9.20) and a reduced risk among those with a lower level of SHBG (OR, 0.60; 95% CI, 0.18-1.97). The overall results of the study suggest that Arg399Gln polymorphism of the XRCC1 gene alone may not play a substantial role in the risk of breast cancer among Chinese women. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/14693738/A_population_based_case_control_study_of_the_Arg399Gln_polymorphism_in_DNA_repair_gene_XRCC1_and_risk_of_breast_cancer_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&amp;pmid=14693738 DB - PRIME DP - Unbound Medicine ER -