title: Interactions between genetic variants in the adiponectin, adiponectin receptor 1 and environmental factors on the risk of colorectal cancer.
abstract: BACKGROUND
  Metabolic syndrome traits play an important role in the development of colorectal cancer. Adipokines, key metabolic syndrome cellular mediators, when abnormal, may induce carcinogenesis.
  
  
  RESULTS
  To investigate whether polymorphisms of important adipokines, adiponectin (ADIPOQ) and its receptors, either alone or in combination with environmental factors, are implicated in colorectal cancer, a two-stage case-control study was conducted. In the first stage, we evaluated 24 tag single nucleotide polymorphisms (tag SNPs) across ADIPOQ ligand and two ADIPOQ receptors (ADIPOR1 and ADIPOR2) among 470 cases and 458 controls. One SNP with promising association was then analyzed in stage 2 among 314 cases and 355 controls. In our study, ADIPOQ rs1063538 was consistently associated with increased colorectal cancer risk, with an odds ratio (OR) of 1.94 (95%CI: 1.48-2.54) for CC genotype compared with TT genotype. In two-factor gene-environment interaction analyses, rs1063538 presented significant interactions with smoking status, family history of cancer and alcohol use, with ORs of 4.52 (95%CI: 2.78-7.34), 3.18 (95%CI: 1.73-5.82) and 1.97 (95%CI: 1.27-3.04) for smokers, individuals with family history of cancer or drinkers with CC genotype compared with non-smokers, individuals without family history of cancer or non-drinkers with TT genotype, respectively. Multifactor gene-environment interactions analysis revealed significant interactions between ADIPOQ rs1063538, ADIPOR1 rs1539355, smoking status and BMI. Individuals carrying one, two and at least three risk factors presented 1.18-fold (95%CI:0.89-fold to 1.58-fold), 1.87-fold (95%CI: 1.38-fold to 2.54-fold) and 4.39-fold (95%CI: 2.75-fold to 7.01-fold) increased colorectal cancer risk compared with those who without risk factor, respectively (P(trend) <0.0001).
  
  
  CONCLUSIONS
  Our results suggest that variants in ADIPOQ may contribute to increased colorectal cancer risk in Chinese and this contribution may be modified by environmental factors, such as smoking status, family history of cancer and BMI.
authors.affiliation: Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.forename: Sheng
authors.initials: S
authors.lastname: Wei
authors.forename: Jie-Yun
authors.initials: JY
authors.lastname: Yin
authors.forename: Hao
authors.initials: H
authors.lastname: Xiang
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Ji-Gui
authors.initials: JG
authors.lastname: Chen
authors.forename: Xia-Wen
authors.initials: XW
authors.lastname: Zheng
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Huang
authors.forename: Bei-Bei
authors.initials: BB
authors.lastname: Zhu
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Duan
authors.forename: Rui
authors.initials: R
authors.lastname: Rui
authors.forename: Bei-Fang
authors.initials: BF
authors.lastname: Yang
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Sun
authors.forename: Duo-Shuang
authors.initials: DS
authors.lastname: Xie
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Xu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Miao
authors.forename: Shao-Fa
authors.initials: SF
authors.lastname: Nie
mesh_terms: D052242:Adiponectin / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics; D005190:Family; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
chemical_list: C475418:ADIPOR1 protein, human; D052242:Adiponectin; D054419:Receptors, Adiponectin
references.citation: Stat Med. 2004 May 15;23(9):1439-53
references.pmid: 15116352
references.citation: JAMA. 2008 Oct 1;300(13):1523-31
references.pmid: 18827209
references.citation: Methods Mol Biol. 2001;170:103-16
references.pmid: 11357675
references.citation: Ann Hum Genet. 2007 Jul;71(Pt 4):526-36
references.pmid: 17274802
references.citation: Eur J Endocrinol. 2010 Aug;163(2):251-7
references.pmid: 20516205
references.citation: J Natl Cancer Inst. 2005 Nov 16;97(22):1688-94
references.pmid: 16288122
references.citation: N Engl J Med. 2003 Apr 24;348(17):1625-38
references.pmid: 12711737
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2476-81
references.pmid: 14983034
references.citation: Eur Heart J. 2009 Aug;30(15):1885-93
references.pmid: 19468010
references.citation: Ai Zheng. 2009 Sep;28(9):897-902
references.pmid: 19728903
references.citation: Obesity (Silver Spring). 2009 Apr;17(4):737-44
references.pmid: 19165155
references.citation: J Cardiol. 2009 Apr;53(2):219-25
references.pmid: 19304126
references.citation: J Clin Endocrinol Metab. 2003 Mar;88(3):993-7
references.pmid: 12629074
references.citation: Mol Endocrinol. 2010 Jul;24(7):1441-52
references.pmid: 20444885
references.citation: Clin Chem. 2010 Jan;56(1):34-43
references.pmid: 19910504
references.citation: Endocr Relat Cancer. 2008 Mar;15(1):289-99
references.pmid: 18310295
references.citation: BMC Med Genet. 2011 Jan 10;12:5
references.pmid: 21219602
references.citation: Cancer Res. 2010 Jul 1;70(13):5430-7
references.pmid: 20516125
references.citation: Nature. 2003 Jun 12;423(6941):762-9
references.pmid: 12802337
references.citation: Biochem J. 2008 Feb 1;409(3):623-33
references.pmid: 18177270
references.citation: Int J Colorectal Dis. 2010 Feb;25(2):205-12
references.pmid: 19888587
references.citation: Cancer Res. 1997 Nov 1;57(21):4787-94
references.pmid: 9354440
references.citation: Am J Epidemiol. 2004 Apr 15;159(8):732-9
references.pmid: 15051582
references.citation: J Natl Cancer Inst. 2010 Mar 17;102(6):391-400
references.pmid: 20208017
references.citation: Am J Clin Nutr. 2007 Sep;86(3):s858-66
references.pmid: 18265479
references.citation: J Natl Cancer Inst. 2006 Jul 5;98(13):920-31
references.pmid: 16818856
references.citation: Int J Cancer. 1998 Oct 5;78(2):161-5
references.pmid: 9754646
references.citation: Cancer Causes Control. 2004 Aug;15(6):581-9
references.pmid: 15280637
references.citation: Int J Cancer. 2010 Dec 15;127(12):2893-917
references.pmid: 21351269
references.citation: World J Gastroenterol. 2010 Mar 14;16(10):1252-7
references.pmid: 20222170
references.citation: Gastroenterology. 2011 Jun;140(7):2000-8, 2008.e1-2
references.pmid: 21334339
references.citation: Cancer Epidemiol Biomarkers Prev. 2011 May;20(5):779-92
references.pmid: 21357378
references.citation: J Nutr Biochem. 2006 Mar;17(3):145-56
references.pmid: 16426829
references.citation: Cancer Res. 2008 May 1;68(9):3178-84
references.pmid: 18451143
references.citation: J Urol. 2005 Oct;174(4 Pt 1):1266-70
references.pmid: 16145390
references.citation: Mol Carcinog. 2010 Jul;49(7):700-9
references.pmid: 20564347
references.citation: Hum Mutat. 2001 Apr;17(4):296-304
references.pmid: 11295828
references.citation: Int J Cancer. 2010 Dec 15;127(12):2758-67
references.pmid: 21351255
references.citation: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references.pmid: 20610543
references.citation: J Natl Cancer Inst. 2002 Jul 3;94(13):972-80
references.pmid: 12096082
references.citation: Diabetes. 2002 Feb;51(2):536-40
references.pmid: 11812766
references.citation: Diabet Med. 2008 Apr;25(4):400-6
references.pmid: 18294218
references.citation: Intern Med. 2011;50(7):707-12
references.pmid: 21467702
references.citation: PLoS One. 2010 Aug 05;5(8):e11987
references.pmid: 20700533
references.citation: J Clin Endocrinol Metab. 2006 Jun;91(6):2310-6
references.pmid: 16551730
references.citation: J Natl Cancer Inst. 2004 Apr 7;96(7):546-53
references.pmid: 15069117
references.citation: Metabolism. 2011 Sep;60(9):1234-43
references.pmid: 21397927
references.citation: Oncogene. 2002 Oct 21;21(48):7326-40
references.pmid: 12379876
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Apr;13(4):553-9
references.pmid: 15066919
references.citation: Br J Cancer. 2006 May 8;94(9):1221-5
references.pmid: 16570048
references.citation: J Clin Endocrinol Metab. 2010 Jul;95(7):3517-21
references.pmid: 20382687
references.citation: Am J Clin Nutr. 2007 Jan;85(1):26-34
references.pmid: 17209173
references.citation: Int J Cancer. 2006 Jan 15;118(2):458-66
references.pmid: 16049963
references.citation: Trends Pharmacol Sci. 2005 Feb;26(2):69-76
references.pmid: 15681023
references.citation: Biochem Biophys Res Commun. 2006 Jun 23;345(1):271-9
references.pmid: 16678125