Table 1.
Summary of Variant/Varianta Data Used in Meta-Analyses of the Association Between Cytochrome P-450 2D6 (CYP2D6) Genotype and Risk of Breast Cancer Recurrence or Mortality
| First Author, Year (Reference No.) | Country/Region | Major Variant Allele | Relative Riskb | 95% CI | Weight,c % | DNAd | No. of Casese | No. of Personsf | ||
|---|---|---|---|---|---|---|---|---|---|---|
| V/V | W/W | V/V | W/W | |||||||
| Sirachainan, 2012 (55) | Thailand | *10 | 0.28 | 0.01, 2.6 | 1.7 | Nonneoplastic | 11 | 5 | 8 | 1 |
| Markkula, 2014 (56) | Sweden | *4 | 0.5 | 0.07, 3.82 | 2.0 | Nonneoplastic | 1.0* | 20 | 16.1* | 154 |
| Okishiro, 2009 (57) | Japan | *10 | 0.6 | 0.18, 1.98 | 4.1 | Nonneoplastic | 3 | 40 | ||
| Gor, 2010 (58) | Multicenter | *4 | 0.99 | 0.5, 1.99 | 6.6 | Nonneoplastic | 224 | 19 | ||
| Mwinyi, 2014 (59) | Switzerland | *4 | 1.0 | 0.14, 7.1 | 2.1 | Nonneoplastic | 1 | 6 | 5 | 30 |
| Abraham, 2010 (60) | United Kingdom | *4 | 1.13 | 0.84, 1.54 | 8.8 | Nonneoplastic | 23 | 302 | 130 | 1,950 |
| Schroth, 2007g (61) | Germany | *4 | 1.63 | 1.07, 2.46 | 8.3 | Nonneoplastic | 10 | 30 | 17 | 118 |
| Chamnanphon, 2013 (62) | Thailand | *10 | 1.68 | 0.60, 4.73 | 4.8 | Nonneoplastic | 7 | 18 | 7 | 13 |
| Goetz, 2013h (63) | Austria | *4 | 2.45 | 1.05, 5.73 | 5.7 | Nonneoplastic | ||||
| Bijl, 2009 (64) | The Netherlands | *4 | 4.10 | 1.10, 15.9 | 3.6 | Nonneoplastic | 3 | 17 | 4 | 52 |
| Xu, 2008 (65) | China | *10 | 4.70 | 1.10, 20 | 3.3 | Nonneoplastic | ||||
| Park, 2011 (66) | South Korea | *10 | 5.59 | 0.93, 33.5 | 2.4 | Nonneoplastic | 49 | 10 | 179 | 31 |
| Damodaran, 2012 (67) | India | *4, *10 | 7.29 | 2.92, 18.2 | 5.4 | Nonneoplastic | 8 | 121 | ||
| Kiyotani, 2010 (68) | Japan | *10 | 9.52 | 2.79, 32.5 | 4.0 | Nonneoplastic | 18 | 3 | 63 | 84 |
| Sukasem, 2012 (69) | Thailand | *10 | 10.5 | 1.56, 70.8 | 2.2 | Nonneoplastic | 10 | 8 | ||
| Teh, 2012 (70) | Malaysia | *10 | 13.1 | 1.54, 109 | 1.9 | Nonneoplastic | 12 | 33 | 1 | 24 |
| Regan, 2012 (27) | Multicenter | *4 | 0.57 | 0.26, 1.23 | 6.2 | Tumor | 7 | 60 | 76 | 609 |
| Rae, 2012 (26) | Multicenter | *4 | 0.99 | 0.48, 2.08 | 6.3 | Tumor | 24 | 38 | 58 | 317 |
| Dezentje, 2013 (72) | The Netherlands | *4 | 1.01 | 0.57, 1.78 | 7.4 | Tumor | 3.8* | 47 | 27.5* | 345 |
| Lash, 2011 (28) | Denmark | *4 | 1.4 | 0.84, 2.3 | 7.8 | Tumor | 41 | 299 | 30 | 308 |
| Goetz, 2005g (46) | United States | *4 | 1.85 | 0.76, 4.52 | 5.5 | Tumor | 6 | 13 | ||
Abbreviations: CI, confidence interval; V, variant; W, wild-type.
a As described in the text, wild-type was defined as a functional allele or inferred extensive metabolizer phenotype; variant was defined as a reduced or eliminated function allele or poor metabolizer phenotype. Therefore, wild-type/wild-type (the reference group) encompassed extensive metabolizers and ultrametabolizers, and variant/variant encompassed poor metabolizers.
b Adjusted hazard ratio, rate ratio, or odds ratio reported in the original publication.
c The study's relative weight, expressed as a percentage, in the random-effects meta-analysis.
d Nonneoplastic = DNA extracted from nonneoplastic tissue; tumor = DNA extracted from tumor-infiltrated tissue.
e Number of cases in genotype category. When reported as an integer, this number was abstracted from the manuscript. When reported as a fraction with an accompanying asterisk (*), this number was imputed from the total number of reported cases and the reported estimate of association. Where no number is shown, the number was not reported, and it was not imputed because the study used DNA extracted from nonneoplastic tissue and thus was not subjected to quantitative bias analysis.
f For cohort study designs, number of persons at risk within the genotype category. For case-control study designs, number of controls within the genotype category. When reported as an integer, this number was abstracted from the manuscript. When reported as a fraction with an accompanying asterisk (*), this number was imputed from the total number of reported subjects and reported genotype proportions. Where no number is shown, the number was not available from the original manuscript.
g Data from the studies by Schroth et al. (61) and Goetz et al. (46) were subsequently pooled (90). We used the results from the original studies.
h Goetz et al. extracted DNA from formalin-fixed, paraffin-embedded specimens but wrote that extraction and assay methods were specifically designed “to overcome the potential problems related to somatic deletion of the CYP2D6 chromosomal locus on 22q13” (i.e., loss of heterozygosity) (63, p. 501). Thus, we classified this study's results with those of the nonneoplastic group.