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ADRB2 G–G haplotype associated with breast cancer risk among Hispanic and non-Hispanic white women: interaction with type 2 diabetes and obesity

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Abstract

Introduction

Polymorphisms in the beta-2-adrenergic receptor (ADRB2) gene have been studied in relation to risk of type 2 diabetes and obesity, risk factors that have received increased attention in relation to breast cancer. We evaluated the hypothesis that ADRB2 variants (rs1042713, rs1042714) are associated with breast cancer risk in non-Hispanic white (NHW) and Hispanic (H) women using data from a population-based case–control study conducted in the southwestern United States.

Methods

Data on lifestyle and medical history, and blood samples, were collected during in-person interviews for incident primary breast cancer cases (1,244 NHW, 606 H) and controls (1,330 NHW, 728 H). ADRB2 genotypes for rs1042713(G/A) and rs1042714(G/C) were determined using TaqMan assays. The associations of each variant and corresponding haplotypes with breast cancer were estimated using multivariable logistic regression.

Results

Two copies compared to one or zero copies of the ADRB2 G–G haplotype were associated with increased breast cancer risk for NHW women [odds ratio (OR), 1.95; 95 % confidence interval (95 % CI), 1.26–3.01], but with reduced risk for H women [OR, 0.74; 95 % CI, 0.50–1.09]. Effect estimates were strengthened for women with a body mass index (BMI) ≥25 kg/m2 [H: OR, 0.50; 95 % CI, 0.31–0.82; NHW: OR, 3.85; 95 % CI, 1.88–7.88] and for H women with a history of diabetes [H: OR, 0.32; 95 % CI, 0.12–0.89].

Conclusions

These data suggest that ethnicity modifies the association between the ADRB2 G–G haplotype and breast cancer risk, and being overweight or obese enhances the divergence of risk between H and NHW women.

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References

  1. Brinton LLJ, Devesa SS (2002) Cancer of the breast epidemiology of breast cancer, 5th edn. Saunders, Philadelphia

    Google Scholar 

  2. Lahmann PH, Hoffmann K, Allen N, van Gils CH, Khaw KT, Tehard B, Berrino F, Tjonneland A, Bigaard J, Olsen A, Overvad K, Clavel-Chapelon F, Nagel G, Boeing H, Trichopoulos D, Economou G, Bellos G, Palli D, Tumino R, Panico S, Sacerdote C, Krogh V, Peeters PH, Bueno-de-Mesquita HB, Lund E, Ardanaz E, Amiano P, Pera G, Quiros JR, Martinez C, Tormo MJ, Wirfalt E, Berglund G, Hallmans G, Key TJ, Reeves G, Bingham S, Norat T, Biessy C, Kaaks R, Riboli E (2004) Body size and breast cancer risk: findings from the European prospective investigation into cancer and nutrition (EPIC). Int J Cancer 111(5):762–771. doi:10.1002/ijc.20315

    Article  PubMed  CAS  Google Scholar 

  3. Rinaldi SKT, Peeters PHM, Lahmann PH (2006) Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: a study within the EPIC cohort. Int J Cancer 118:2832–2839

    Article  PubMed  CAS  Google Scholar 

  4. Morimoto LM, White E, Chen Z, Chlebowski RT, Hays J, Kuller L, Lopez AM, Manson J, Margolis KL, Muti PC, Stefanick ML, McTiernan A (2002) Obesity, body size, and risk of postmenopausal breast cancer: the women’s health initiative (United States). Cancer Causes Control 13(8):741–751

    Article  PubMed  Google Scholar 

  5. Michels KB, Terry KL, Willett WC (2006) Longitudinal study on the role of body size in premenopausal breast cancer. Arch Intern Med 166(21):2395–2402. doi:10.1001/archinte.166.21.2395

    Article  PubMed  Google Scholar 

  6. Wolf I, Sadetzki S, Catane R, Karasik A, Kaufman B (2005) Diabetes mellitus and breast cancer. Lancet Oncol 6(2):103–111. doi:10.1016/S1470-2045(05)01736-5

    Article  PubMed  CAS  Google Scholar 

  7. Caballero AE (2005) Diabetes in the Hispanic or Latino population: genes, environment, culture, and more. Curr Diab Rep 5(3):217–225

    Article  PubMed  Google Scholar 

  8. Caballero AE (2007) Type 2 diabetes in the Hispanic or Latino population: challenges and opportunities. Curr Opin Endocrinol Diabetes Obes 14(2):151–157. doi:10.1097/MED.0b013e32809f9531

    Article  PubMed  Google Scholar 

  9. Perez-Escamilla R, Putnik P (2007) The role of acculturation in nutrition, lifestyle, and incidence of type 2 diabetes among Latinos. J Nutr 137(4):860–870

    PubMed  CAS  Google Scholar 

  10. Hines LM, Risendal B, Slattery ML, Baumgartner KB, Giuliano AR, Sweeney C, Rollison DE, Byers T (2010) Comparative analysis of breast cancer risk factors among Hispanic and non-Hispanic white women. Cancer 116(13):3215–3223. doi:10.1002/cncr.25154

    Article  PubMed  Google Scholar 

  11. Sweeney CW, Wolff RK, Byers T, Baumgartner KB, Giuliano AR, Herrick JS, Murtaugh MA, Samowitz WS, Slattery MK (2007) Genetic admixture among hispanics and candidate gene polymorphisms: potential for confounding in a breast cancer study. Cancer Epidemiol Biomarkers Prev 16(1):142–150

    Article  PubMed  CAS  Google Scholar 

  12. Large V, Hellstrom L, Reynisdottir S, Lonnqvist F, Eriksson P, Lannfelt L, Arner P (1997) Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. J Clin Invest 100(12):3005–3013. doi:10.1172/JCI119854

    Article  PubMed  CAS  Google Scholar 

  13. Litonjua AA, Gong L, Duan QL, Shin J, Moore MJ, Weiss ST, Johnson JA, Klein TE, Altman RB (2010) Very important pharmacogene summary ADRB2. Pharmacogenet Genom 20(1):64–69. doi:10.1097/FPC.0b013e328333dae6

    Article  CAS  Google Scholar 

  14. Chang TJ, Tsai MH, Jiang YD, Lee B, Lee KC, Lin JY, Chiu KC, Tai TY, Chuang LM (2002) The Arg16Gly polymorphism of human beta2-adrenoreceptor is associated with type 2 diabetes in Taiwanese people. Clin Endocrinol (Oxf) 57(5):685–690

    Article  CAS  Google Scholar 

  15. Ishiyama-Shigemoto S, Yamada K, Yuan X, Ichikawa F, Nonaka K (1999) Association of polymorphisms in the beta2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus. Diabetologia 42(1):98–101

    Article  PubMed  CAS  Google Scholar 

  16. Pereira AC, Floriano MS, Mota GF, Cunha RS, Herkenhoff FL, Mill JG, Krieger JE (2003) Beta2 adrenoceptor functional gene variants, obesity, and blood pressure level interactions in the general population. Hypertension 42(4):685–692. doi:10.1161/01.HYP.0000085648.65419.17

    Article  PubMed  CAS  Google Scholar 

  17. Lange LA, Norris JM, Langefeld CD, Nicklas BJ, Wagenknecht LE, Saad MF, Bowden DW (2005) Association of adipose tissue deposition and beta-2 adrenergic receptor variants: the IRAS family study. Int J Obes (Lond) 29(5):449–457. doi:10.1038/sj.ijo.0802883

    CAS  Google Scholar 

  18. Ruiz JR, Larrarte E, Margareto J, Ares R, Labayen I (2011) Role of beta-adrenergic receptor polymorphisms on body weight and body composition response to energy restriction in obese women: preliminary results. Obesity (Silver Spring) 19(1):212–215. doi:10.1038/oby.2010.130

    Article  CAS  Google Scholar 

  19. Jalba MS, Rhoads GG, Demissie K (2008) Association of codon 16 and codon 27 beta 2-adrenergic receptor gene polymorphisms with obesity: a meta-analysis. Obesity (Silver Spring) 16(9):2096–2106

    Article  CAS  Google Scholar 

  20. Arner P, Hoffstedt J (1999) Adrenoceptor genes in human obesity. J Intern Med 245(6):667–672

    Article  PubMed  CAS  Google Scholar 

  21. Kim SH, Kim DJ, Seo IA, Min YK, Lee MS, Kim KW, Lee MK (2002) Significance of beta2-adrenergic receptor gene polymorphism in obesity and type 2 diabetes mellitus in Korean subjects. Metabolism 51(7):833–837

    Article  PubMed  CAS  Google Scholar 

  22. Gjesing AP, Andersen G, Burgdorf KS, Borch-Johnsen K, Jorgensen T, Hansen T, Pedersen O (2007) Studies of the associations between functional beta2-adrenergic receptor variants and obesity, hypertension and type 2 diabetes in 7,808 white subjects. Diabetologia 50(3):563–568. doi:10.1007/s00125-006-0578-8

    Article  PubMed  CAS  Google Scholar 

  23. Huang XE, Hamajima N, Saito T, Matsuo K, Mizutani M, Iwata H, Iwase T, Miura S, Mizuno T, Tokudome S, Tajima K (2001) Possible association of beta2- and beta3-adrenergic receptor gene polymorphisms with susceptibility to breast cancer. Breast Cancer Res 3(4):264–269

    Article  PubMed  CAS  Google Scholar 

  24. Feigelson HS, Teras LR, Diver WR, Tang W, Patel AV, Stevens VL, Calle EE, Thun MJ, Bouzyk M (2008) Genetic variation in candidate obesity genes ADRB2, ADRB3, GHRL, HSD11B1, IRS1, IRS2, and SHC1 and risk for breast cancer in the Cancer Prevention Study II. Breast Cancer Res 10(4):R57. doi:10.1186/bcr2114

    Article  PubMed  Google Scholar 

  25. Slattery ML, Edwards S, Murtaugh MA, Sweeney C, Herrick J, Byers T, Giuliano AR, Baumgartner KB (2007) Physical activity and breast cancer risk among women in the southwestern United States. Ann Epidemiol 17(5):342–353. doi:10.1016/j.annepidem.2006.10.017

    Article  PubMed  Google Scholar 

  26. Slattery ML, Sweeney C, Edwards S, Herrick J, Baumgartner K, Wolff R, Murtaugh M, Baumgartner R, Giuliano A, Byers T (2007) Body size, weight change, fat distribution and breast cancer risk in Hispanic and non-Hispanic white women. Breast Cancer Res Treat 102(1):85–101. doi:10.1007/s10549-006-9292-y

    Article  PubMed  Google Scholar 

  27. Slattery ML, Sweeney C, Herrick J, Wolff R, Baumgartner K, Giuliano A, Byers T (2007) ESR1, AR, body size, and breast cancer risk in Hispanic and non-Hispanic white women living in the Southwestern United States. Breast Cancer Res Treat 105(3):327–335. doi:10.1007/s10549-006-9453-z

    Article  PubMed  Google Scholar 

  28. Slattery ML, Sweeney C, Wolff R, Herrick J, Baumgartner K, Giuliano A, Byers T (2007) Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. Breast Cancer Res Treat 104(2):197–209. doi:10.1007/s10549-006-9403-9

    Article  PubMed  CAS  Google Scholar 

  29. Howard CA, Samet JM, Buechley RW, Schrag SD, Key CR (1983) Survey research in New Mexico Hispanics: some methodological issues. Am J Epidemiol 117(1):27–34

    PubMed  CAS  Google Scholar 

  30. Ainsworth BE, Irwin ML, Addy CL, Whitt MC, Stolarczyk LM (1999) Moderate physical activity patterns of minority women: the cross-cultural activity participation study. J Womens Health Gend Based Med 8(6):805–813. doi:10.1089/152460999319129

    Article  PubMed  CAS  Google Scholar 

  31. Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM, Strath SJ, O’Brien WL, Bassett DR Jr, Schmitz KH, Emplaincourt PO, Jacobs DR Jr, Leon AS (2000) Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 32(9 Suppl):S498–S504

    PubMed  CAS  Google Scholar 

  32. Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164(4):1567–1587

    PubMed  CAS  Google Scholar 

  33. Pritchard JK, Stephens M, Donnelly P (2000) Inference of population structure using multilocus genotype data. Genetics 155(2):945–959

    PubMed  CAS  Google Scholar 

  34. Slattery ML, Curtin K, Sweeney C, Wolff RK, Baumgartner RN, Baumgartner KB, Giuliano AR, Byers T (2008) Modifying effects of IL-6 polymorphisms on body size-associated breast cancer risk. Obesity (Silver Spring) 16(2):339–347. doi:10.1038/oby.2007.44

    Article  CAS  Google Scholar 

  35. Zaykin DV, Westfall PH, Young SS, Karnoub MA, Wagner MJ, Ehm MG (2002) Testing association of statistically inferred haplotypes with discrete and continuous traits in samples of unrelated individuals. Hum Hered 53(2):79–91

    Article  PubMed  Google Scholar 

  36. Rothman KJ, Sander G (1998) Case-control studies. In: Winters R, O’Connor E (eds) Modern epidemiology, 2nd edn. Lippincott Williams & Wilkins, Philadelphia, pp 93–114

  37. Hosmer D, Lemeshow S (1989) Applied logistic regression. Wiley, New York

    Google Scholar 

  38. Jewell NP (2003) Statistics for epidemiology. Chapman & Hall/CRC Press, Boca Raton

    Google Scholar 

  39. Westfall PH, Randall TD, Rom D, Wolfinger RD, Hochberg Y (1999) Multiple comparisons and multiple tests using SAS. SAS Institute Inc., Cary

    Google Scholar 

  40. Cagliani R, Fumagalli M, Pozzoli U, Riva S, Comi GP, Torri F, Macciardi F, Bresolin N, Sironi M (2009) Diverse evolutionary histories for beta-adrenoreceptor genes in humans. Am J Hum Genet 85(1):64–75. doi:10.1016/j.ajhg.2009.06.005

    Article  PubMed  CAS  Google Scholar 

  41. Slattery ML, Baumgartner KB, Giuliano AR, Byers T, Herrick JS, Wolff RK (2011) Replication of five GWAS-identified loci and breast cancer risk among Hispanic and non-Hispanic white women living in the Southwestern United States. Breast Cancer Res Treat. doi:10.1007/s10549-011-1498-y

  42. Lai H, Lai S, Ma F, Meng L, Trapido E (2003) Prevalence and spectrum of p53 mutations in white Hispanic and non-Hispanic women with breast cancer. Breast Cancer Res Treat 81(1):53–60. doi:10.1023/A:1025422905655

    Article  PubMed  CAS  Google Scholar 

  43. Cakir Y, Plummer HK III, Tithof PK, Schuller HM (2002) Beta-adrenergic and arachidonic acid-mediated growth regulation of human breast cancer cell lines. Int J Oncol 21(1):153–157

    PubMed  CAS  Google Scholar 

  44. Hong SH, Avis I, Vos MD, Martinez A, Treston AM, Mulshine JL (1999) Relationship of arachidonic acid metabolizing enzyme expression in epithelial cancer cell lines to the growth effect of selective biochemical inhibitors. Cancer Res 59(9):2223–2228

    PubMed  CAS  Google Scholar 

  45. Plummer HK III, Yu Q, Cakir Y, Schuller HM (2004) Expression of inwardly rectifying potassium channels (GIRKs) and beta-adrenergic regulation of breast cancer cell lines. BMC Cancer 4:93. doi:10.1186/1471-2407-4-93

    Article  PubMed  Google Scholar 

  46. Vandewalle B, Revillion F, Lefebvre J (1990) Functional beta-adrenergic receptors in breast cancer cells. J Cancer Res Clin Oncol 116(3):303–306

    Article  PubMed  CAS  Google Scholar 

  47. Draoui A, Vandewalle B, Hornez L, Revillion F, Lefebvre J (1991) Beta-adrenergic receptors in human breast cancer: identification, characterization and correlation with progesterone and estradiol receptors. Anticancer Res 11(2):677–680

    PubMed  CAS  Google Scholar 

  48. Larsson SC, Mantzoros CS, Wolk A (2007) Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 121(4):856–862. doi:10.1002/ijc.22717

    Article  PubMed  CAS  Google Scholar 

  49. Pharoah PD, Dunning AM, Ponder BA, Easton DF (2004) Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer 4(11):850–860. doi:10.1038/nrc1476

    Article  PubMed  CAS  Google Scholar 

  50. Ioannidis JP, Trikalinos TA, Khoury MJ (2006) Implications of small effect sizes of individual genetic variants on the design and interpretation of genetic association studies of complex diseases. Am J Epidemiol 164(7):609–614. doi:10.1093/aje/kwj259

    Article  PubMed  Google Scholar 

  51. Newton-Cheh C, Hirschhorn JN (2005) Genetic association studies of complex traits: design and analysis issues. Mutat Res 573(1–2):54–69. doi:10.1016/j.mrfmmm.2005.01.006

    PubMed  CAS  Google Scholar 

  52. Sweeney C, Edwards SL, Baumgartner KB, Herrick JS, Palmer LE, Murtaugh MA, Stroup A, Slattery ML (2007) Recruiting Hispanic women for a population-based study: validity of surname search and characteristics of nonparticipants. Am J Epidemiol 166(10):1210–1219. doi:10.1093/aje/kwm192

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was funded by grants: CA 078682, CA 078762, CA 078552, CA 078802, and R01CA140002. This research also was supported by the Utah Cancer Registry, which is funded by Contract #N01-PC-67000 from the National Cancer Institute, with additional support from the State of Utah Department of Health, the New Mexico Tumor Registry, and the Arizona and Colorado cancer registries, funded by the Centers for Disease Control and Prevention National Program of Cancer Registries and additional state support. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute. This study was completed and also funded under the Susan G. Komen Breast Cancer Disparities Epidemiology Research Training Program: University of Louisville (Grant #KG09092). We would also like to acknowledge the contributions of Sandra Edwards, Roger Edwards, Stephanie Denkhoff, Erica Wolff, and Michael Hoffman.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, 485 E. Gray St., Louisville, KY, 40202, USA

    Avonne Connor, Richard N. Baumgartner, Richard A. Kerber, Elizabeth O’Brien, Shesh N. Rai & Kathy B. Baumgartner

  2. Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA

    Roger K. Wolff & Martha L. Slattery

  3. Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA

    Betsy C. Risendal & Tim E. Byers

  4. Department of Community and Behavioral Health, Colorado School of Public Health, Aurora, CO, USA

    Betsy C. Risendal & Tim E. Byers

  5. Department of Cancer Epidemiology and Genetics, H. Lee Moffit Cancer Center and Research Institute, Tampa, FL, USA

    Anna R. Giuliano

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  1. Avonne Connor
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Correspondence to Avonne Connor.

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Connor, A., Baumgartner, R.N., Kerber, R.A. et al. ADRB2 G–G haplotype associated with breast cancer risk among Hispanic and non-Hispanic white women: interaction with type 2 diabetes and obesity. Cancer Causes Control 23, 1653–1663 (2012). https://doi.org/10.1007/s10552-012-0043-6

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