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Interaction between genetic variations in DNA repair genes and plasma folate on breast cancer risk.
Cancer Epidemiol Biomarkers Prev. 2004 Apr; 13(4):520-4.CE

Abstract

Folate status has been inversely associated with breast cancer risk. Because folate deficiency can cause DNA damage, such as uracil misincorporation, single strand breaks, and double strand breaks, genetic polymorphisms in base excision repair and double strand break repair genes may lead to variation in DNA repair proficiency and modify the effect of folate on breast cancer risk. We prospectively investigated the a priori hypothesized interaction between plasma folate levels and five nonsynonymous polymorphisms in the XRCC1, XRCC2, and XRCC3 genes on breast cancer risk in a nested case-control study within the Nurses' Health Study (712 case-control pairs). Suggestive evidence of interaction was seen for two of these polymorphisms. Compared with the reference group of non-carriers in the lowest quartile of plasma folate, the reduction in risk (66%) was statistically significant among XRCC1 194Trp carriers in the highest quartile (multivariate odds ratio, 0.34; 95% confidence interval, 0.16-0.72). The inverse association between XRCC1 194Trp and breast cancer risk was attenuated by lower plasma folate status. The inverse association between plasma folate level and breast cancer risk was stronger among 194Trp carriers (P, trend = 0.01) than non-carriers (P, trend = 0.09). We also observed that the positive association between the XRCC2 188His allele and breast cancer risk was only significant in women in the lowest plasma folate quartile (carriers versus non-carriers; multivariate odds ratio, 2.04; 95% confidence interval, 1.05-3.97), and this excess risk was abolished among those with higher plasma folate levels. Moreover, the inverse association between plasma folate level and breast cancer risk was stronger among XRCC2 188His carriers (P, trend = 0.004) than non-carriers (P, trend = 0.09). Although none of the statistical tests for interaction was significant, these data give some support for the hypothesis that genetic variations in DNA repair genes may modify the relation between plasma folate level and breast cancer risk.

Authors+Show Affiliations

Department of Nutrition, Harvard Center for Cancer Prevention, Harvard School of Public Health, Room 105, Building II, 665 Huntington Avenue, Boston, MA 02115, USA. jhan@hsph.harvard.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15066914

Citation

Han, Jiali, et al. "Interaction Between Genetic Variations in DNA Repair Genes and Plasma Folate On Breast Cancer Risk." Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, vol. 13, no. 4, 2004, pp. 520-4.
Han J, Hankinson SE, Zhang SM, et al. Interaction between genetic variations in DNA repair genes and plasma folate on breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2004;13(4):520-4.
Han, J., Hankinson, S. E., Zhang, S. M., De Vivo, I., & Hunter, D. J. (2004). Interaction between genetic variations in DNA repair genes and plasma folate on breast cancer risk. Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored By the American Society of Preventive Oncology, 13(4), 520-4.
Han J, et al. Interaction Between Genetic Variations in DNA Repair Genes and Plasma Folate On Breast Cancer Risk. Cancer Epidemiol Biomarkers Prev. 2004;13(4):520-4. PubMed PMID: 15066914.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interaction between genetic variations in DNA repair genes and plasma folate on breast cancer risk. AU - Han,Jiali, AU - Hankinson,Susan E, AU - Zhang,Shumin M, AU - De Vivo,Immaculata, AU - Hunter,David J, PY - 2004/4/7/pubmed PY - 2005/2/16/medline PY - 2004/4/7/entrez SP - 520 EP - 4 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 - 13 IS - 4 N2 - Folate status has been inversely associated with breast cancer risk. Because folate deficiency can cause DNA damage, such as uracil misincorporation, single strand breaks, and double strand breaks, genetic polymorphisms in base excision repair and double strand break repair genes may lead to variation in DNA repair proficiency and modify the effect of folate on breast cancer risk. We prospectively investigated the a priori hypothesized interaction between plasma folate levels and five nonsynonymous polymorphisms in the XRCC1, XRCC2, and XRCC3 genes on breast cancer risk in a nested case-control study within the Nurses' Health Study (712 case-control pairs). Suggestive evidence of interaction was seen for two of these polymorphisms. Compared with the reference group of non-carriers in the lowest quartile of plasma folate, the reduction in risk (66%) was statistically significant among XRCC1 194Trp carriers in the highest quartile (multivariate odds ratio, 0.34; 95% confidence interval, 0.16-0.72). The inverse association between XRCC1 194Trp and breast cancer risk was attenuated by lower plasma folate status. The inverse association between plasma folate level and breast cancer risk was stronger among 194Trp carriers (P, trend = 0.01) than non-carriers (P, trend = 0.09). We also observed that the positive association between the XRCC2 188His allele and breast cancer risk was only significant in women in the lowest plasma folate quartile (carriers versus non-carriers; multivariate odds ratio, 2.04; 95% confidence interval, 1.05-3.97), and this excess risk was abolished among those with higher plasma folate levels. Moreover, the inverse association between plasma folate level and breast cancer risk was stronger among XRCC2 188His carriers (P, trend = 0.004) than non-carriers (P, trend = 0.09). Although none of the statistical tests for interaction was significant, these data give some support for the hypothesis that genetic variations in DNA repair genes may modify the relation between plasma folate level and breast cancer risk. SN - 1055-9965 UR - https://www.unboundmedicine.com/medline/citation/15066914/Interaction_between_genetic_variations_in_DNA_repair_genes_and_plasma_folate_on_breast_cancer_risk_ L2 - http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15066914 DB - PRIME DP - Unbound Medicine ER -