title: Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study.
abstract: Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P(ARTP) = 0.01), for premenopausal women (P(ARTP) = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P(ARTP) = 0.03) and ER-/PR- tumors (P(ARTP) = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process.
authors.affiliation: Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT 84108, USA, Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Av. Universidad No. 655, Col. Sta. Ma. Ahuacatitlán, Cuernavaca Morelos CP 62100, México, Cancer Prevention Institute of California, Fremont, CA 84108, USA, Division of Epidemiology, Department of Health Research and Policy and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 62508, USA, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Department of Biology, University of Colorado at Colorado Springs, 1420 Austin Bluffs Parkway, Colorado Springs, CO 80918, USA, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90089, USA and Department of Epidemiology and Population Health, School of Public Health & Information Sciences, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 90089-9031, USA marty.slattery@hsc.utah.edu.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Slattery
authors.affiliation: Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT 84108, USA, Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Av. Universidad No. 655, Col. Sta. Ma. Ahuacatitlán, Cuernavaca Morelos CP 62100, México, Cancer Prevention Institute of California, Fremont, CA 84108, USA, Division of Epidemiology, Department of Health Research and Policy and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 62508, USA, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Department of Biology, University of Colorado at Colorado Springs, 1420 Austin Bluffs Parkway, Colorado Springs, CO 80918, USA, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90089, USA and Department of Epidemiology and Population Health, School of Public Health & Information Sciences, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 90089-9031, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Herrick
authors.affiliation: Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Av. Universidad No. 655, Col. Sta. Ma. Ahuacatitlán, Cuernavaca Morelos CP 62100, México.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Torres-Mejia
authors.affiliation: Cancer Prevention Institute of California, Fremont, CA 84108, USA, Division of Epidemiology, Department of Health Research and Policy and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 62508, USA.
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.affiliation: Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Giuliano
authors.affiliation: Department of Biology, University of Colorado at Colorado Springs, 1420 Austin Bluffs Parkway, Colorado Springs, CO 80918, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Hines
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90089, USA and.
authors.forename: Mariana C
authors.initials: MC
authors.lastname: Stern
authors.affiliation: Department of Epidemiology and Population Health, School of Public Health & Information Sciences, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 90089-9031, USA.
authors.forename: Kathy B
authors.initials: KB
authors.lastname: Baumgartner
authors.affiliation: Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT 84108, USA, Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Av. Universidad No. 655, Col. Sta. Ma. Ahuacatitlán, Cuernavaca Morelos CP 62100, México, Cancer Prevention Institute of California, Fremont, CA 84108, USA, Division of Epidemiology, Department of Health Research and Policy and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 62508, USA, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Department of Biology, University of Colorado at Colorado Springs, 1420 Austin Bluffs Parkway, Colorado Springs, CO 80918, USA, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90089, USA and Department of Epidemiology and Population Health, School of Public Health & Information Sciences, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 90089-9031, USA.
authors.forename: Angela P
authors.initials: AP
authors.lastname: Presson
authors.affiliation: Department of Medicine, University of Utah, 383 Colorow, Salt Lake City, UT 84108, USA, Instituto Nacional de Salud Pública, Centro de Investigación en Salud Poblacional, Av. Universidad No. 655, Col. Sta. Ma. Ahuacatitlán, Cuernavaca Morelos CP 62100, México, Cancer Prevention Institute of California, Fremont, CA 84108, USA, Division of Epidemiology, Department of Health Research and Policy and Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 62508, USA, Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA, Department of Biology, University of Colorado at Colorado Springs, 1420 Austin Bluffs Parkway, Colorado Springs, CO 80918, USA, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90089, USA and Department of Epidemiology and Population Health, School of Public Health & Information Sciences, James Graham Brown Cancer Center, University of Louisville, Louisville, KY 90089-9031, USA.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Wolff
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D054625:Healthcare Disparities; D006801:Humans; D015994:Incidence; D007378:Interleukins / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
chemical_list: D007378:Interleukins