Combined genetic and nutritional risk models of triple negative breast cancer

Eunkyung Lee, Edward A. Levine, Vivian I. Franco, Glenn O. Allen, Feng Gong, Yanbin Zhang, Jennifer Hu

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Triple negative breast cancer (TNBC) presents clinical challenges due to unknown etiology, lack of treatment targets, and poor prognosis. We examined combined genetic and nutritional risk models of TNBC in 354 breast cancer cases. We evaluated 18 DNA-repair nonsynonymous single nucleotide polymorphisms (nsSNPs) and dietary/nutritional intakes. Multivariate Adaptive Regression Splines models were used to select nutrients of interest and define cut-off values for logistic regression models. Our results suggest that TNBC was associated with 6 DNA-repair nsSNPs, ERCC4 R415Q (rs1800067), MSH3 R940Q (rs184967), MSH6 G39E (rs1042821), POLD1 R119H (rs1726801), XRCC1 R194W (rs1799782), and XPC A499V (rs2228000) and/or deficiencies in 3 micronutrients (zinc, folate, and β-carotene). Combined analyses of these 6 nsSNPs and 3 micronutrients showed significant association with TNBC: odds ratios = 2.77 (95% confidence interval = 1.01-7.64) and 10.89 (95% confidence interval = 3.50-33.89) for 2 and at least 3 risk factors, respectively. To the best of our knowledge, this is the first study to suggest that multiple genetic and nutritional factors are associated with TNBC, particularly in combination. Our findings, if validated in larger studies, will have important clinical implication that dietary modulations and/or micronutrient supplementations may prevent or reverse TNBC phenotype, so tumors can be treated with less toxic therapeutic strategies, particularly in genetically susceptible women.

Original languageEnglish (US)
Pages (from-to)955-963
Number of pages9
JournalNutrition and Cancer
Volume66
Issue number6
DOIs
StatePublished - 2014

Fingerprint

Nutrigenomics
Triple Negative Breast Neoplasms
Micronutrients
Single Nucleotide Polymorphism
DNA Repair
Logistic Models
Confidence Intervals
Poisons
Carotenoids
Folic Acid
Zinc
Odds Ratio
Breast Neoplasms
Phenotype
Food
Therapeutics

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

Cite this

Combined genetic and nutritional risk models of triple negative breast cancer. / Lee, Eunkyung; Levine, Edward A.; Franco, Vivian I.; Allen, Glenn O.; Gong, Feng; Zhang, Yanbin; Hu, Jennifer.

In: Nutrition and Cancer, Vol. 66, No. 6, 2014, p. 955-963.

Research output: Contribution to journalArticle

Lee, Eunkyung ; Levine, Edward A. ; Franco, Vivian I. ; Allen, Glenn O. ; Gong, Feng ; Zhang, Yanbin ; Hu, Jennifer. / Combined genetic and nutritional risk models of triple negative breast cancer. In: Nutrition and Cancer. 2014 ; Vol. 66, No. 6. pp. 955-963.
@article{469f5c5e056b480e9ed61a8b325dec79,
title = "Combined genetic and nutritional risk models of triple negative breast cancer",
abstract = "Triple negative breast cancer (TNBC) presents clinical challenges due to unknown etiology, lack of treatment targets, and poor prognosis. We examined combined genetic and nutritional risk models of TNBC in 354 breast cancer cases. We evaluated 18 DNA-repair nonsynonymous single nucleotide polymorphisms (nsSNPs) and dietary/nutritional intakes. Multivariate Adaptive Regression Splines models were used to select nutrients of interest and define cut-off values for logistic regression models. Our results suggest that TNBC was associated with 6 DNA-repair nsSNPs, ERCC4 R415Q (rs1800067), MSH3 R940Q (rs184967), MSH6 G39E (rs1042821), POLD1 R119H (rs1726801), XRCC1 R194W (rs1799782), and XPC A499V (rs2228000) and/or deficiencies in 3 micronutrients (zinc, folate, and β-carotene). Combined analyses of these 6 nsSNPs and 3 micronutrients showed significant association with TNBC: odds ratios = 2.77 (95{\%} confidence interval = 1.01-7.64) and 10.89 (95{\%} confidence interval = 3.50-33.89) for 2 and at least 3 risk factors, respectively. To the best of our knowledge, this is the first study to suggest that multiple genetic and nutritional factors are associated with TNBC, particularly in combination. Our findings, if validated in larger studies, will have important clinical implication that dietary modulations and/or micronutrient supplementations may prevent or reverse TNBC phenotype, so tumors can be treated with less toxic therapeutic strategies, particularly in genetically susceptible women.",
author = "Eunkyung Lee and Levine, {Edward A.} and Franco, {Vivian I.} and Allen, {Glenn O.} and Feng Gong and Yanbin Zhang and Jennifer Hu",
year = "2014",
doi = "10.1080/01635581.2014.932397",
language = "English (US)",
volume = "66",
pages = "955--963",
journal = "Nutrition and Cancer",
issn = "0163-5581",
publisher = "Routledge",
number = "6",

}

TY - JOUR

T1 - Combined genetic and nutritional risk models of triple negative breast cancer

AU - Lee, Eunkyung

AU - Levine, Edward A.

AU - Franco, Vivian I.

AU - Allen, Glenn O.

AU - Gong, Feng

AU - Zhang, Yanbin

AU - Hu, Jennifer

PY - 2014

Y1 - 2014

N2 - Triple negative breast cancer (TNBC) presents clinical challenges due to unknown etiology, lack of treatment targets, and poor prognosis. We examined combined genetic and nutritional risk models of TNBC in 354 breast cancer cases. We evaluated 18 DNA-repair nonsynonymous single nucleotide polymorphisms (nsSNPs) and dietary/nutritional intakes. Multivariate Adaptive Regression Splines models were used to select nutrients of interest and define cut-off values for logistic regression models. Our results suggest that TNBC was associated with 6 DNA-repair nsSNPs, ERCC4 R415Q (rs1800067), MSH3 R940Q (rs184967), MSH6 G39E (rs1042821), POLD1 R119H (rs1726801), XRCC1 R194W (rs1799782), and XPC A499V (rs2228000) and/or deficiencies in 3 micronutrients (zinc, folate, and β-carotene). Combined analyses of these 6 nsSNPs and 3 micronutrients showed significant association with TNBC: odds ratios = 2.77 (95% confidence interval = 1.01-7.64) and 10.89 (95% confidence interval = 3.50-33.89) for 2 and at least 3 risk factors, respectively. To the best of our knowledge, this is the first study to suggest that multiple genetic and nutritional factors are associated with TNBC, particularly in combination. Our findings, if validated in larger studies, will have important clinical implication that dietary modulations and/or micronutrient supplementations may prevent or reverse TNBC phenotype, so tumors can be treated with less toxic therapeutic strategies, particularly in genetically susceptible women.

AB - Triple negative breast cancer (TNBC) presents clinical challenges due to unknown etiology, lack of treatment targets, and poor prognosis. We examined combined genetic and nutritional risk models of TNBC in 354 breast cancer cases. We evaluated 18 DNA-repair nonsynonymous single nucleotide polymorphisms (nsSNPs) and dietary/nutritional intakes. Multivariate Adaptive Regression Splines models were used to select nutrients of interest and define cut-off values for logistic regression models. Our results suggest that TNBC was associated with 6 DNA-repair nsSNPs, ERCC4 R415Q (rs1800067), MSH3 R940Q (rs184967), MSH6 G39E (rs1042821), POLD1 R119H (rs1726801), XRCC1 R194W (rs1799782), and XPC A499V (rs2228000) and/or deficiencies in 3 micronutrients (zinc, folate, and β-carotene). Combined analyses of these 6 nsSNPs and 3 micronutrients showed significant association with TNBC: odds ratios = 2.77 (95% confidence interval = 1.01-7.64) and 10.89 (95% confidence interval = 3.50-33.89) for 2 and at least 3 risk factors, respectively. To the best of our knowledge, this is the first study to suggest that multiple genetic and nutritional factors are associated with TNBC, particularly in combination. Our findings, if validated in larger studies, will have important clinical implication that dietary modulations and/or micronutrient supplementations may prevent or reverse TNBC phenotype, so tumors can be treated with less toxic therapeutic strategies, particularly in genetically susceptible women.

UR - http://www.scopus.com/inward/record.url?scp=85027942575&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85027942575&partnerID=8YFLogxK

U2 - 10.1080/01635581.2014.932397

DO - 10.1080/01635581.2014.932397

M3 - Article

C2 - 25023197

AN - SCOPUS:85027942575

VL - 66

SP - 955

EP - 963

JO - Nutrition and Cancer

JF - Nutrition and Cancer

SN - 0163-5581

IS - 6

ER -