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A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk.
Breast Cancer Res 2005; 7(6):R1168-73BC

Abstract

INTRODUCTION

The gene XRCC1 (X-ray repair cross-complementing group 1) encodes a protein involved in DNA base excision repair. Two non-synonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) have been shown to alter DNA repair capacity in some studies in vitro. However, results of previous association studies of these two XRCC1 variants and breast cancer have been inconsistent. We examined the association between polymorphisms in XRCC1 and breast cancer in the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort, a large prospective study of cancer incidence in the USA.

METHODS

Among the 21,965 women who were cancer-free in 1992 and gave blood between 1998 and 2001, 502 postmenopausal breast cancer cases were diagnosed between 1992 and 2001; 502 controls were matched to cases on age, race/ethnicity, and date of blood collection. Genotyping on DNA extracted from buffy coat was performed with Taqman. Conditional logistic regression was used to examine the association between each polymorphism and breast cancer risk controlling for breast cancer risk factors. We also examined whether factors associated with DNA damage, such as smoking and antioxidant intake, modified the association between XRCC1 polymorphisms and breast cancer.

RESULTS

We observed a significant inverse association between Trp194 carriers (Trp/Trp and Trp/Arg) compared with Trp194 non-carriers in relation to breast cancer (Arg/Arg) (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95). The inverse association between breast cancer and Trp194 carriers compared with non-carriers was slightly stronger among smokers (OR 0.47, 95% CI 0.24 to 0.94) than never smokers (OR 0.78, 95% CI 0.43 to 1.40). An increased risk associated with the Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was observed only among women who reported ever smoking cigarettes (OR 2.76, 95% CI 1.36 to 5.63), and not in women who were lifelong non-smokers (OR 0.64, 95% CI 0.33 to 1.26). No other factor examined modified the association between XRCC1 polymorphisms and breast cancer risk.

CONCLUSION

Our results support the hypothesis that genetic variation in XRCC1, particularly in Arg194Trp, may influence postmenopausal breast cancer risk. In our study, genetic variation in XRCC1 Arg399Gln was associated with breast cancer risk only among women with a history of smoking cigarettes.

Authors+Show Affiliations

Department of Epidemiology and Surveillance Research, American Cancer Society, 1599 Clifton Road NE, Atlanta, GA 30309, USA. apatel@cancer.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16457697

Citation

Patel, Alpa V., et al. "A Prospective Study of XRCC1 (X-ray Cross-complementing Group 1) Polymorphisms and Breast Cancer Risk." Breast Cancer Research : BCR, vol. 7, no. 6, 2005, pp. R1168-73.
Patel AV, Calle EE, Pavluck AL, et al. A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk. Breast Cancer Res. 2005;7(6):R1168-73.
Patel, A. V., Calle, E. E., Pavluck, A. L., Feigelson, H. S., Thun, M. J., & Rodriguez, C. (2005). A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk. Breast Cancer Research : BCR, 7(6), pp. R1168-73.
Patel AV, et al. A Prospective Study of XRCC1 (X-ray Cross-complementing Group 1) Polymorphisms and Breast Cancer Risk. Breast Cancer Res. 2005;7(6):R1168-73. PubMed PMID: 16457697.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A prospective study of XRCC1 (X-ray cross-complementing group 1) polymorphisms and breast cancer risk. AU - Patel,Alpa V, AU - Calle,Eugenia E, AU - Pavluck,Alexandre L, AU - Feigelson,Heather Spencer, AU - Thun,Michael J, AU - Rodriguez,Carmen, Y1 - 2005/11/21/ PY - 2005/08/15/received PY - 2005/10/14/revised PY - 2005/10/24/accepted PY - 2006/2/7/pubmed PY - 2006/2/28/medline PY - 2006/2/7/entrez SP - R1168 EP - 73 JF - Breast cancer research : BCR JO - Breast Cancer Res. VL - 7 IS - 6 N2 - INTRODUCTION: The gene XRCC1 (X-ray repair cross-complementing group 1) encodes a protein involved in DNA base excision repair. Two non-synonymous polymorphisms in XRCC1 (Arg194Trp and Arg399Gln) have been shown to alter DNA repair capacity in some studies in vitro. However, results of previous association studies of these two XRCC1 variants and breast cancer have been inconsistent. We examined the association between polymorphisms in XRCC1 and breast cancer in the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort, a large prospective study of cancer incidence in the USA. METHODS: Among the 21,965 women who were cancer-free in 1992 and gave blood between 1998 and 2001, 502 postmenopausal breast cancer cases were diagnosed between 1992 and 2001; 502 controls were matched to cases on age, race/ethnicity, and date of blood collection. Genotyping on DNA extracted from buffy coat was performed with Taqman. Conditional logistic regression was used to examine the association between each polymorphism and breast cancer risk controlling for breast cancer risk factors. We also examined whether factors associated with DNA damage, such as smoking and antioxidant intake, modified the association between XRCC1 polymorphisms and breast cancer. RESULTS: We observed a significant inverse association between Trp194 carriers (Trp/Trp and Trp/Arg) compared with Trp194 non-carriers in relation to breast cancer (Arg/Arg) (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95). The inverse association between breast cancer and Trp194 carriers compared with non-carriers was slightly stronger among smokers (OR 0.47, 95% CI 0.24 to 0.94) than never smokers (OR 0.78, 95% CI 0.43 to 1.40). An increased risk associated with the Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was observed only among women who reported ever smoking cigarettes (OR 2.76, 95% CI 1.36 to 5.63), and not in women who were lifelong non-smokers (OR 0.64, 95% CI 0.33 to 1.26). No other factor examined modified the association between XRCC1 polymorphisms and breast cancer risk. CONCLUSION: Our results support the hypothesis that genetic variation in XRCC1, particularly in Arg194Trp, may influence postmenopausal breast cancer risk. In our study, genetic variation in XRCC1 Arg399Gln was associated with breast cancer risk only among women with a history of smoking cigarettes. SN - 1465-542X UR - https://www.unboundmedicine.com/medline/citation/16457697/A_prospective_study_of_XRCC1__X_ray_cross_complementing_group_1__polymorphisms_and_breast_cancer_risk_ L2 - https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1355 DB - PRIME DP - Unbound Medicine ER -