title: Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival.
abstract: Obesity is a strong risk factor for breast cancer in postmenopausal women and adverse prognostic indicator regardless of menopausal status. Leptin is an important regulator of adipose tissue mass and has been associated with tumor cell growth. Leptin exerts its effects through interaction with the leptin receptor (LEPR). We investigated whether genetic variations in the leptin (LEP) and LEPR genes are associated with risk of breast cancer, or once diagnosed, with survival. The polymorphisms LEP G-2548A and LEPR Q223R were characterized in population-based study consisting of mostly European-American women. The study examined 1,065 women diagnosed with first, primary invasive breast cancer between 1996 and 1997. Controls were 1,108 women frequency matched to the cases by 5-year age group. A modest increase in risk of developing breast cancer was associated with the LEP -2548AA genotype when compared to the LEP -2548GG genotype (age-adjusted OR = 1.30; 95% CI = 1.01-1.66). This association was stronger among postmenopausal women who were obese (OR = 1.86; 95% CI = 0.95-3.64) although the interaction was of borderline statistical significance (P = 0.07). We found no evidence of an association with polymorphisms of either LEP or LEPR in relation to all-cause or breast cancer-specific mortality among women with breast cancer (mean follow-up time = 66.7 months). The effects of these genotypes on breast cancer risk and mortality did not vary significantly when stratified by menopausal status. In summary, our results show that a common variant in LEP may be associated with the risk of developing breast cancer supporting the hypothesis that leptin is involved in breast carcinogenesis.
authors.affiliation: Department of Nutrition, School of Public Health, University of North Carolina, Chapel Hill, NC 27599-7461, USA. becki@unc.edu
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Cleveland
authors.forename: Marilie D
authors.initials: MD
authors.lastname: Gammon
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Long
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.forename: Sybil M
authors.initials: SM
authors.lastname: Eng
authors.forename: Susan L
authors.initials: SL
authors.lastname: Teitelbaum
authors.forename: Alfred I
authors.initials: AI
authors.lastname: Neugut
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality; D016022:Case-Control Studies; D002423:Cause of Death; D005060:Europe / Q000208:ethnology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D020738:Leptin / Q000235:genetics* / Q000502:physiology; D008593:Menopause; D009518:New York / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D054411:Receptors, Leptin / Q000235:genetics*; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin
references.citation: Med Sci Monit. 2002 Dec;8(12):RA282-92
references.pmid: 12503048
references.citation: Int J Cancer. 1999 Feb 9;80(4):523-6
references.pmid: 9935151
references.citation: J Clin Endocrinol Metab. 2001 Sep;86(9):4434-9
references.pmid: 11549688
references.citation: Am J Clin Nutr. 1999 Apr;69(4):584-96
references.pmid: 10197558
references.citation: Metabolism. 2004 Jul;53(7):879-85
references.pmid: 15254881
references.citation: J Clin Oncol. 2004 Sep 1;22(17):3558-62
references.pmid: 15337805
references.citation: Am J Epidemiol. 2005 Jul 15;162(2):101-14
references.pmid: 15972940
references.citation: Clin Cancer Res. 2004 Jul 1;10(13):4325-31
references.pmid: 15240518
references.citation: Cancer Lett. 2006 Jun 8;237(1):137-42
references.pmid: 16011872
references.citation: Prostate. 2004 May 15;59(3):268-74
references.pmid: 15042602
references.citation: Ann Hum Genet. 2000 Sep;64(Pt 5):391-4
references.pmid: 11281277
references.citation: World Health Organ Tech Rep Ser. 1995;854:1-452
references.pmid: 8594834
references.citation: Eur J Cancer. 2006 May;42(8):1188-93
references.pmid: 16630717
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1803-11
references.pmid: 17855698
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1686-91
references.pmid: 16030102
references.citation: Cell Res. 2000 Jun;10(2):81-92
references.pmid: 10896170
references.citation: J Steroid Biochem Mol Biol. 2006 Jun;99(4-5):189-96
references.pmid: 16621515
references.citation: Horm Metab Res. 2002 Jul;34(7):355-9
references.pmid: 12189581
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Jun;14(6):1576-8
references.pmid: 15941977
references.citation: Breast Cancer Res Treat. 2002 Jun;74(3):235-54
references.pmid: 12206514
references.citation: Clin Endocrinol (Oxf). 2003 Feb;58(2):213-9
references.pmid: 12580938
references.citation: Nat Med. 1995 Sep;1(9):953-6
references.pmid: 7585224
references.citation: Breast Cancer Res Treat. 2004 Aug;86(3):191-6
references.pmid: 15567935
references.citation: J Clin Oncol. 2002 Feb 15;20(4):1128-43
references.pmid: 11844838
references.citation: J Natl Cancer Inst. 2002 Nov 20;94(22):1704-11
references.pmid: 12441326
references.citation: Nutr Cancer. 2003;45(1):1-16
references.pmid: 12791499
references.citation: Genomics. 1991 Dec;11(4):1054-62
references.pmid: 1686014
references.citation: Nature. 1994 Dec 1;372(6505):425-32
references.pmid: 7984236
references.citation: J Clin Endocrinol Metab. 2000 Jan;85(1):29-34
references.pmid: 10634359
references.citation: J Clin Oncol. 2005 Sep 1;23(25):6037-42
references.pmid: 16135472
references.citation: Br J Cancer. 2005 Oct 3;93(7):811-6
references.pmid: 16160698
references.citation: Breast Cancer Res Treat. 2006 Jul;98(2):157-65
references.pmid: 16502016
references.citation: Int J Oncol. 2002 Dec;21(6):1285-92
references.pmid: 12429979
references.citation: Int J Cancer. 2006 Mar 15;118(6):1414-9
references.pmid: 16206269
references.citation: Diabetologia. 1978 Mar;14(3):141-8
references.pmid: 350680
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Apr;12(4):380-3
references.pmid: 12692114
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 May;13(5):779-86
references.pmid: 15159310
references.citation: World Health Organ Tech Rep Ser. 2000;894:i-xii, 1-253
references.pmid: 11234459
references.citation: Am J Epidemiol. 2005 Aug 1;162(3):229-37
references.pmid: 15987723
references.citation: BMC Cancer. 2006 Feb 20;6:38
references.pmid: 16504019
references.citation: J Biol Chem. 2006 Sep 8;281(36):26320-8
references.pmid: 16825198
references.citation: Cancer Causes Control. 2000 May;11(5):383-8
references.pmid: 10877331