CYP2D6 Phenotype and Breast Cancer Outcomes: A Bias Analysis and Meta-Analysis.

Autor:	MacLehose RF; Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota., Ahern TP; Department of Surgery, Larner College of Medicine at the University of Vermont, Burlington, Vermont., Collin LJ; Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia., Li A; Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota., Lash TL; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
Jazyk:	angličtina
Zdroj:	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2024 Nov 14, pp. OF1-OF10. Date of Electronic Publication: 2024 Nov 14.
DOI:	10.1158/1055-9965.EPI-24-0755
Abstrakt:	Background: We evaluated the impact of systematic bias due to loss of heterozygosity (LOH) and incomplete phenotyping in studies examining the relationship between CYP2D6 variants and breast cancer recurrence among women treated with tamoxifen. Methods: We performed a systematic review of the literature on tamoxifen, CYP2D6 variants, and breast cancer recurrence. A quantitative bias analysis was performed to adjust for LOH and incomplete phenotyping. Bias-adjusted results were then combined in a meta-analysis. Results: Thirty-three studies informed the bias analysis and meta-analysis on CYP2D6 variants and breast cancer recurrence and/or mortality. An unadjusted meta-analysis suggested increased risk of recurrence and/or mortality for poor relative to normal metabolizers [RR = 1.28; 95% simulation interval (SI), 1.04-1.58] with substantial heterogeneity (I2 = 27%; P for heterogeneity = 0.07). Adjusting for LOH and incomplete genotyping resulted in a slight change in the effect estimate and a decrease in heterogeneity (RR = 1.34; 95% SI, 1.10-1.63; I2 = 0%; P for heterogeneity = 0.17). Intermediate metabolizers had a slightly increased risk of recurrence and/or mortality relative to normal metabolizers (RR = 1.15; 95% SI, 1.00-1.34; I2 = 0%; P for heterogeneity = 0.89). Conclusions: Adjusting for biases such as LOH and incomplete genotyping reduced observed heterogeneity between studies. Individuals with poor CYP2D6 phenotypes were at increased risk for breast cancer outcomes compared with those with normal phenotypes. Impact: Reduction in CYP2D6 activity was associated with an increased risk of breast cancer recurrence and/or mortality, and results underscore the importance of quantitatively adjusting for biases when aggregating study results. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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