TY - JOUR
T1 - Genetic variants in the MRPS30 region and postmenopausal breast cancer risk
AU - Huang, Ying
AU - Ballinger, Dennis G.
AU - Dai, James Y.
AU - Peters, Ulrike
AU - Hinds, David A.
AU - Cox, David R.
AU - Beilharz, Erica
AU - Chlebowski, Rowan T.
AU - Rossouw, Jacques E.
AU - McTiernan, Anne
AU - Rohan, Thomas
AU - Prentice, Ross L.
N1 - Funding Information:
Decisions concerning study design, data collection and analysis, interpretation of the results, the preparation of the manuscript, or the decision to submit the manuscript for publication resided with committees composed of WHI investigators that included NHLBI representatives. Program Office: (National Heart, Lung, and Blood Institute, Bethesda, MD, USA) Jacques Rossouw, Shari Ludlam, Joan McGowan, Leslie Ford, and Nancy Geller. Clinical Coordinating Center: (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) Ross Prentice, Garnet Anderson, Andrea LaCroix, Charles L Kooperberg; (Medical Research Labs, Highland Heights, KY, USA) Evan Stein; (University of California at San Francisco, San Francisco, CA, USA) Steven Cummings. Clinical Centers: (Albert Einstein College of Medicine, Bronx, NY, USA) Sylvia Wassertheil-Smoller; (Baylor College of Medicine, Houston, TX, USA) Haleh Sangi-Haghpeykar; (Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA) JoAnn E Manson; (Brown University, Providence, RI, USA) Charles B Eaton; (Emory University, Atlanta, GA, USA) Lawrence S Phillips; (Fred Hutchinson Cancer Research Center, Seattle, WA, USA) Shirley Beresford; (George Washington University Medical Center, Washington, DC, USA) Lisa Martin; (Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA) Rowan Chlebowski; (Kaiser Permanente Center for Health Research, Portland, OR, USA) Erin LeBlanc; (Kaiser Permanente Division of Research, Oakland, CA, USA) Bette Caan; (Medical College of Wisconsin, Milwaukee, WI, USA) Jane Morley Kotchen; (MedStar Research Institute/Howard University, Washington, DC, USA) Barbara V Howard; (Northwestern University, Chicago/ Evanston, IL, USA) Linda Van Horn; (Rush Medical Center, Chicago, IL, USA) Henry Black; (Stanford Prevention Research Center, Stanford, CA, USA). Marcia L Stefanick; (State University of New York at Stony Brook, Stony Brook, NY, USA) Dorothy Lane; (The Ohio State University, Columbus, OH, USA) Rebecca Jackson; (University of Alabama at Birmingham, Birmingham, AL, USA) Cora E Lewis; (University of Arizona, Tucson/Phoenix, AZ, USA) Cynthia A Thomson; (University at Buffalo, Buffalo, NY, USA) Jean Wactawski-Wende; (University of California at Davis, Sacramento, CA, USA) John Robbins; (University of California at Irvine, CA, USA) F Allan Hubbell; (University of California at Los Angeles, Los Angeles, CA, USA) Lauren Nathan; (University of California at San Diego, LaJolla/Chula Vista, CA, USA) Robert D Langer; (University of Cincinnati, Cincinnati, OH, USA) Margery Gass; (University of Florida, Gainesville/Jacksonville, FL, USA) Marian Limacher; (University of Hawaii, Honolulu, HI, USA) J David Curb; (University of Iowa, Iowa City/Davenport, IA, USA) Robert Wallace; (University of Massachusetts/Fallon Clinic, Worcester, MA, USA) Judith Ockene; (University of Medicine and Dentistry of New Jersey, Newark, NJ, USA) Norman Lasser; (University of Miami, Miami, FL, USA) Mary Jo O’Sullivan; (University of Minnesota, Minneapolis, MN, USA) Karen Margolis; (University of Nevada, Reno, NV) Robert Brunner; (University of North Carolina, Chapel Hill, NC, USA) Gerardo Heiss; (University of Pittsburgh, Pittsburgh, PA, USA) Lewis Kuller; (University of Tennessee Health Science Center, Memphis, TN, USA) Karen C Johnson; (University of Texas Health Science Center, San Antonio, TX, USA) Robert Brzyski; (University of Wisconsin, Madison, WI, USA) Gloria E Sarto; (Wake Forest University School of Medicine, Winston-Salem, NC, USA) Mara Vitolins; (Wayne State University School of Medicine/Hutzel Hospital, Detroit, MI, USA) Michael S Simon. Women’s Health Initiative Memory Study: (Wake Forest University School of Medicine, Winston-Salem, NC, USA) Sally Shumaker. This work was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [contracts HHSN268200764314C, N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-19, 32122, 42107-26, 42129-32, and 44221]. Clinical Trials Registration: ClinicalTrials.gov identifier, NCT00000611. The work of Dr Prentice was partially supported by grants CA53996 and CA148065 from the National Cancer Institute.
PY - 2011/6/24
Y1 - 2011/6/24
N2 - Background: Genome-wide association studies have identified several genomic regions that are associated with breast cancer risk, but these provide an explanation for only a small fraction of familial breast cancer aggregation. Genotype by environment interactions may contribute further to such explanation, and may help to refine the genomic regions of interest.Methods: We examined genotypes for 4,988 SNPs, selected from recent genome-wide studies, and four randomized hormonal and dietary interventions among 2,166 women who developed invasive breast cancer during the intervention phase of the Women's Health Initiative (WHI) clinical trial (1993 to 2005), and one-to-one matched controls. These SNPs derive from 3,224 genomic regions having pairwise squared correlation (r2) between adjacent regions less than 0.2. Breast cancer and SNP associations were identified using a test statistic that combined evidence of overall association with evidence for SNPs by intervention interaction.Results: The combined 'main effect' and interaction test led to a focus on two genomic regions, the fibroblast growth factor receptor two (FGFR2) and the mitochondrial ribosomal protein S30 (MRPS30) regions. The ranking of SNPs by significance level, based on this combined test, was rather different from that based on the main effect alone, and drew attention to the vicinities of rs3750817 in FGFR2 and rs7705343 in MRPS30. Specifically, rs7705343 was included with several FGFR2 SNPs in a group of SNPs having an estimated false discovery rate < 0.05. In further analyses, there were suggestions (nominal P < 0.05) that hormonal and dietary intervention hazard ratios varied with the number of minor alleles of rs7705343.Conclusions: Genotype by environment interaction information may help to define genomic regions relevant to disease risk. Combined main effect and intervention interaction analyses raise novel hypotheses concerning the MRPS30 genomic region and the effects of hormonal and dietary exposures on postmenopausal breast cancer risk.
AB - Background: Genome-wide association studies have identified several genomic regions that are associated with breast cancer risk, but these provide an explanation for only a small fraction of familial breast cancer aggregation. Genotype by environment interactions may contribute further to such explanation, and may help to refine the genomic regions of interest.Methods: We examined genotypes for 4,988 SNPs, selected from recent genome-wide studies, and four randomized hormonal and dietary interventions among 2,166 women who developed invasive breast cancer during the intervention phase of the Women's Health Initiative (WHI) clinical trial (1993 to 2005), and one-to-one matched controls. These SNPs derive from 3,224 genomic regions having pairwise squared correlation (r2) between adjacent regions less than 0.2. Breast cancer and SNP associations were identified using a test statistic that combined evidence of overall association with evidence for SNPs by intervention interaction.Results: The combined 'main effect' and interaction test led to a focus on two genomic regions, the fibroblast growth factor receptor two (FGFR2) and the mitochondrial ribosomal protein S30 (MRPS30) regions. The ranking of SNPs by significance level, based on this combined test, was rather different from that based on the main effect alone, and drew attention to the vicinities of rs3750817 in FGFR2 and rs7705343 in MRPS30. Specifically, rs7705343 was included with several FGFR2 SNPs in a group of SNPs having an estimated false discovery rate < 0.05. In further analyses, there were suggestions (nominal P < 0.05) that hormonal and dietary intervention hazard ratios varied with the number of minor alleles of rs7705343.Conclusions: Genotype by environment interaction information may help to define genomic regions relevant to disease risk. Combined main effect and intervention interaction analyses raise novel hypotheses concerning the MRPS30 genomic region and the effects of hormonal and dietary exposures on postmenopausal breast cancer risk.
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U2 - 10.1186/gm258
DO - 10.1186/gm258
M3 - Article
C2 - 21702935
AN - SCOPUS:79959473080
SN - 1756-994X
VL - 3
JO - Genome Medicine
JF - Genome Medicine
IS - 6
M1 - 42
ER -