title: MAPK genes interact with diet and lifestyle factors to alter risk of breast cancer: the Breast Cancer Health Disparities Study.
abstract: Mitogen-activated protein kinases (MAPK) are integration points for multiple biochemical signals. We evaluated 13 MAPK genes with breast cancer risk and determined if diet and lifestyle factors mediated risk. Data from 3 population-based case-control studies conducted in Southwestern United States, California, and Mexico included 4183 controls and 3592 cases. Percent Indigenous American (IA) ancestry was determined from 104 ancestry informative markers. The adaptive rank truncated product (ARTP) was used to determine the significance of each gene and the pathway with breast cancer risk, by menopausal status, genetic ancestry level, and estrogen receptor (ER)/progesterone receptor (PR) strata. MAP3K9 was associated with breast cancer overall (P(ARTP) = 0.02) with strongest association among women with the highest IA ancestry (P(ARTP) = 0.04). Several SNPs in MAP3K9 were associated with ER+/PR+ tumors and interacted with dietary oxidative balance score (DOBS), dietary folate, body mass index (BMI), alcohol consumption, cigarette smoking, and a history of diabetes. DUSP4 and MAPK8 interacted with calories to alter breast cancer risk; MAPK1 interacted with DOBS, dietary fiber, folate, and BMI; MAP3K2 interacted with dietary fat; and MAPK14 interacted with dietary folate and BMI. The patterns of association across diet and lifestyle factors with similar biological properties for the same SNPs within genes provide support for associations.
authors: a Department of Medicine , University of Utah , Salt Lake City , Utah , USA.
authors: Martha L
authors: ML
authors: Slattery
authors: Abbie
authors: A
authors: Lundgreen
authors: Esther M
authors: EM
authors: John
authors: Gabriela
authors: G
authors: Torres-Mejia
authors: Lisa
authors: L
authors: Hines
authors: Anna R
authors: AR
authors: Giuliano
authors: Kathy B
authors: KB
authors: Baumgartner
authors: Mariana C
authors: MC
authors: Stern
authors: Roger K
authors: RK
authors: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004032:Diet / Q000706:statistics & numerical data*; D004041:Dietary Fats / Q000378:metabolism; D004043:Dietary Fiber / Q000378:metabolism; D054637:Dual-Specificity Phosphatases / Q000235:genetics; D002149:Energy Intake / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D054624:Health Status Disparities; D006801:Humans; D008019:Life Style; D048730:MAP Kinase Kinase Kinase 2; D020930:MAP Kinase Kinase Kinases / Q000235:genetics; D008593:Menopause / Q000235:genetics; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044382:Population Groups / Q000235:genetics; D011960:Receptors, Estrogen / Q000097:blood; D011980:Receptors, Progesterone / Q000097:blood; D012042:Registries; D012307:Risk Factors; D012495:San Francisco; D015206:Southwestern United States
chemical_list: D004041:Dietary Fats; D004043:Dietary Fiber; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D005492:Folic Acid; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048308:Mitogen-Activated Protein Kinase 14; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D048730:MAP Kinase Kinase Kinase 2; D020930:MAP Kinase Kinase Kinases; C482618:MAP3K2 protein, human; C433243:MAP3K9 protein, human; D054639:Mitogen-Activated Protein Kinase Phosphatases; C490583:DUSP4 protein, human; D054637:Dual-Specificity Phosphatases
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