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.
authors.affiliation: a Department of Public Health Sciences and Sylvester Comprehensive Cancer Center , University of Miami Miller School of Medicine , Miami , Florida , USA.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Lee
authors.forename: Edward A
authors.initials: EA
authors.lastname: Levine
authors.forename: Vivian I
authors.initials: VI
authors.lastname: Franco
authors.forename: Glenn O
authors.initials: GO
authors.lastname: Allen
authors.forename: Feng
authors.initials: F
authors.lastname: Gong
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004260:DNA Repair; D004032:Diet; D002149:Energy Intake; D005260:Female; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D044342:Malnutrition / Q000097:blood / Q000150:complications; D018977:Micronutrients / Q000097:blood / Q000172:deficiency; D008875:Middle Aged; D015999:Multivariate Analysis; D015596:Nutrition Assessment; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D011795:Surveys and Questionnaires; D064726:Triple Negative Breast Neoplasms / Q000097:blood / Q000209:etiology / Q000235:genetics*; D015032:Zinc / Q000097:blood / Q000172:deficiency; D019207:beta Carotene / Q000097:blood / Q000172:deficiency
chemical_list: D018977:Micronutrients; D019207:beta Carotene; D005492:Folic Acid; D015032:Zinc