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Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival.

Yin J, Liu H, Liu Z, Wang LE, Chen WV, Zhu D, Amos CI, Fang S, Lee JE, Wei Q - J. Invest. Dermatol. (2014)

Bottom Line: CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001).Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS).The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Medicine, Duke University School of Medicine and Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA [2] Department of Epidemiology and Biostatistics, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT
Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi anemia (FA) pathway involved in DNA crosslink repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2,339 common single-nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 (AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confidence interval (CI)=1.16-2.95, P=0.010), rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings.

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Related in: MedlinePlus

Receiver operating characteristic curves for prediction of CM survival(a) 5-year OS rate and (b) 5-year MSS rate, based on tumor stage and thickness; tumor stage, Breslow thickness plus NUG.
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Figure 2: Receiver operating characteristic curves for prediction of CM survival(a) 5-year OS rate and (b) 5-year MSS rate, based on tumor stage and thickness; tumor stage, Breslow thickness plus NUG.

Mentions: Using multivariate logistic regression and receiver operating characteristic curve, we further evaluated the NUG for its potential to improve the classification of 5-year OS (N = 749; 133 died and 615 alive, and 5-year MSS (N = 732; 95 died due to CM). As shown in Figure 2, including only tumor stage and Breslow thickness as classifiers, the 5-year OS model had an area under the curve (AUC) =73.6%; with the addition of NUG, the AUC was significantly improved to 76.8% (P=0.001, DeLong’s test). With tumor stage and Breslow thickness as classifier, the 5-year MSS had an AUC of 80.6%, which improved to 82.8% after adding NUG (P=0.025, DeLong’s test). This suggests a potential role of the NUG in prediction of patients at risk for death.


Genetic variants in fanconi anemia pathway genes BRCA2 and FANCA predict melanoma survival.

Yin J, Liu H, Liu Z, Wang LE, Chen WV, Zhu D, Amos CI, Fang S, Lee JE, Wei Q - J. Invest. Dermatol. (2014)

Receiver operating characteristic curves for prediction of CM survival(a) 5-year OS rate and (b) 5-year MSS rate, based on tumor stage and thickness; tumor stage, Breslow thickness plus NUG.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4289462&req=5

Figure 2: Receiver operating characteristic curves for prediction of CM survival(a) 5-year OS rate and (b) 5-year MSS rate, based on tumor stage and thickness; tumor stage, Breslow thickness plus NUG.
Mentions: Using multivariate logistic regression and receiver operating characteristic curve, we further evaluated the NUG for its potential to improve the classification of 5-year OS (N = 749; 133 died and 615 alive, and 5-year MSS (N = 732; 95 died due to CM). As shown in Figure 2, including only tumor stage and Breslow thickness as classifiers, the 5-year OS model had an area under the curve (AUC) =73.6%; with the addition of NUG, the AUC was significantly improved to 76.8% (P=0.001, DeLong’s test). With tumor stage and Breslow thickness as classifier, the 5-year MSS had an AUC of 80.6%, which improved to 82.8% after adding NUG (P=0.025, DeLong’s test). This suggests a potential role of the NUG in prediction of patients at risk for death.

Bottom Line: CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001).Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS).The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Medicine, Duke University School of Medicine and Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina, USA [2] Department of Epidemiology and Biostatistics, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

ABSTRACT
Cutaneous melanoma (CM) is the most lethal skin cancer. The Fanconi anemia (FA) pathway involved in DNA crosslink repair may affect CM susceptibility and prognosis. Using data derived from published genome-wide association study, we comprehensively analyzed the associations of 2,339 common single-nucleotide polymorphisms (SNPs) in 14 autosomal FA genes with overall survival (OS) in 858 CM patients. By performing false-positive report probability corrections and stepwise Cox proportional hazards regression analyses, we identified significant associations between CM OS and four putatively functional SNPs: BRCA2 rs10492396 (AG vs. GG: adjusted hazard ratio (adjHR)=1.85, 95% confidence interval (CI)=1.16-2.95, P=0.010), rs206118 (CC vs. TT+TC: adjHR=2.44, 95% CI=1.27-4.67, P=0.007), rs3752447 (CC vs. TT+TC: adjHR=2.10, 95% CI=1.38-3.18, P=0.0005), and FANCA rs62068372 (TT vs. CC+CT: adjHR=1.85, 95% CI=1.27-2.69, P=0.001). Moreover, patients with an increasing number of unfavorable genotypes (NUG) of these loci had markedly reduced OS and melanoma-specific survival (MSS). The final model incorporating with NUG, tumor stage, and Breslow thickness showed an improved discriminatory ability to classify both 5-year OS and 5-year MSS. Additional investigations, preferably prospective studies, are needed to validate our findings.

Show MeSH
Related in: MedlinePlus