{"doi":"10.1158/0008-5472.c.6495129","title":"Data from <i>XRCC1</i> Genotype and Breast Cancer: Functional Studies and Epidemiologic Data Show Interactions between <i>XRCC1</i> Codon 280 His and Smoking","abstract":"<div>Abstract<p>Tobacco smoke produces oxidative and alkylative DNA damage that necessitates repair by base excision repair coordinated by X-ray cross-complementing gene 1 (XRCC1). We investigated whether polymorphisms in <i>XRCC1</i> alter DNA repair capacity and modify breast cancer risk associated with smoking. To show the functionality of the 280His variant, we evaluated single-strand break (SSB) repair capacity of isogenic Chinese hamster ovary cells expressing human forms of XRCC1 after exposure to hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), methyl methanesulfonate (MMS), or camptothecin by monitoring NAD(P)H. We used data from the Carolina Breast Cancer Study (CBCS), a population-based, case-control study that included 2,077 cases (786 African Americans and 1,281 Whites) and 1,818 controls (681 African Americans and 1,137 Whites), to examine associations among <i>XRCC1</i> codon 194, 280, and 399 genotypes, breast cancer, and smoking. Odds ratios and 95% confidence intervals (95% CI) were calculated by unconditional logistic regression. Only cells expressing the 280His protein accumulated SSB, indicated by NAD(P)H depletion, from both H<sub>2</sub>O<sub>2</sub> and MMS exposures. In the CBCS, positive associations were observed between breast cancer and smoking dose for participants with <i>XRCC1</i> codon 194 Arg/Arg (<i>P</i><sub>trend</sub> = 0.046), 399 Arg/Arg (<i>P</i><sub>trend</sub> = 0.012), and 280 His/His or His/Arg (<i>P</i><sub>trend</sub> = 0.047) genotypes. The 280His allele was in strong linkage disequilibrium with 194Arg (Lewontin's <i>D</i>′ = 1.0) and 399Arg (<i>D</i>′ = 1.0). These data suggest that less common, functional polymorphisms may lie within common haplotypes and drive gene-environment interactions. (Cancer Res 2006; 66(5): 2860-8)</p></div>","journal":null,"year":2023,"id":404240,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1182156,"name":"Scott Winkel","orcid":null,"position":1,"is_corresponding":false},{"id":1182157,"name":"Yoshiko Kubota","orcid":null,"position":2,"is_corresponding":false},{"id":527833,"name":"James A. Swenberg","orcid":null,"position":3,"is_corresponding":false},{"id":211165,"name":"Robert C. Millikan","orcid":null,"position":4,"is_corresponding":false},{"id":432364,"name":"Jun Nakamura","orcid":"0000-0002-1756-7199","position":5,"is_corresponding":false},{"id":533968,"name":"Brian F. Pachkowski","orcid":null,"position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:20:40.264741Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}