Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colorectal Cancer Risk | Colorectal Cancer | JAMA | JAMA Network
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Lee IM, Paffenbarger RS Jr. Quetelet's index and risk of colon cancer in college alumni.  J Natl Cancer Inst. 1992;84(17):1326-13311495102PubMedGoogle ScholarCrossref
Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults.  N Engl J Med. 2003;348(17):1625-163812711737PubMedGoogle ScholarCrossref
MacInnis RJ, English DR, Hopper JL, Haydon AM, Gertig DM, Giles GG. Body size and composition and colon cancer risk in men.  Cancer Epidemiol Biomarkers Prev. 2004;13(4):553-55915066919PubMedGoogle Scholar
Pischon T, Lahmann PH, Boeing H,  et al.  Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC).  J Natl Cancer Inst. 2006;98(13):920-93116818856PubMedGoogle ScholarCrossref
Larsson SC, Wolk A. Obesity and colon and rectal cancer risk: a meta-analysis of prospective studies.  Am J Clin Nutr. 2007;86(3):556-56517823417PubMedGoogle Scholar
Giovannucci E, Pollak MN, Platz EA,  et al.  A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women.  Cancer Epidemiol Biomarkers Prev. 2000;9(4):345-34910794477PubMedGoogle Scholar
Ma J, Giovannucci E, Pollak M,  et al.  A prospective study of plasma C-peptide and colorectal cancer risk in men.  J Natl Cancer Inst. 2004;96(7):546-55315069117PubMedGoogle ScholarCrossref
Sandhu MS, Dunger DB, Giovannucci EL. Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer.  J Natl Cancer Inst. 2002;94(13):972-98012096082PubMedGoogle ScholarCrossref
Wei EK, Ma J, Pollak MN,  et al.  A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women.  Cancer Epidemiol Biomarkers Prev. 2005;14(4):850-85515824155PubMedGoogle ScholarCrossref
Vona-Davis L, Howard-McNatt M, Rose DP. Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer.  Obes Rev. 2007;8(5):395-40817716297PubMedGoogle ScholarCrossref
Drew JE, Farquharson AJ, Padidar S,  et al.  Insulin, leptin, and adiponectin receptors in colon: regulation relative to differing body adiposity independent of diet and in response to dimethylhydrazine.  Am J Physiol Gastrointest Liver Physiol. 2007;293(4):G682-G69117656443PubMedGoogle ScholarCrossref
Williams CJ, Mitsiades N, Sozopoulos E,  et al.  Adiponectin receptor expression is elevated in colorectal carcinomas but not in gastrointestinal stromal tumors.  Endocr Relat Cancer. 2008;15(1):289-29918310295PubMedGoogle ScholarCrossref
Fenton JI, Birmingham JM, Hursting SD, Hord NG. Adiponectin blocks multiple signaling cascades associated with leptin-induced cell proliferation in Apc Min/+ colon epithelial cells.  Int J Cancer. 2008;122(11):2437-244518338750PubMedGoogle ScholarCrossref
Wei EK, Giovannucci E, Fuchs CS, Willett WC, Mantzoros CS. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study.  J Natl Cancer Inst. 2005;97(22):1688-169416288122PubMedGoogle ScholarCrossref
Filippi E, Sentinelli F, Romeo S,  et al.  The adiponectin gene SNP+276G>T associates with early-onset coronary artery disease and with lower levels of adiponectin in younger coronary artery disease patients (age <or=50 years).  J Mol Med. 2005;83(9):711-71915877215PubMedGoogle ScholarCrossref
Hara K, Boutin P, Mori Y,  et al.  Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population.  Diabetes. 2002;51(2):536-54011812766PubMedGoogle ScholarCrossref
Heid IM, Wagner SA, Gohlke H,  et al.  Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians.  Diabetes. 2006;55(2):375-38416443770PubMedGoogle ScholarCrossref
Menzaghi C, Ercolino T, Di PR,  et al.  A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome.  Diabetes. 2002;51(7):2306-231212086965PubMedGoogle ScholarCrossref
Qi L, Doria A, Manson JE,  et al.  Adiponectin genetic variability, plasma adiponectin, and cardiovascular risk in patients with type 2 diabetes.  Diabetes. 2006;55(5):1512-151616644713PubMedGoogle ScholarCrossref
Soccio T, Zhang YY, Bacci S,  et al.  Common haplotypes at the adiponectin receptor 1 (ADIPOR1) locus are associated with increased risk of coronary artery disease in type 2 diabetes.  Diabetes. 2006;55(10):2763-277017003341PubMedGoogle ScholarCrossref
Vasseur F, Helbecque N, Dina C,  et al.  Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians.  Hum Mol Genet. 2002;11(21):2607-261412354786PubMedGoogle ScholarCrossref
Crimmins NA, Martin LJ. Polymorphisms in adiponectin receptor genes ADIPOR1 and ADIPOR2 and insulin resistance.  Obes Rev. 2007;8(5):419-42317716299PubMedGoogle ScholarCrossref
Mitchell MK, Gregersen PK, Johnson S, Parsons R, Vlahov D. The New York Cancer Project: rationale, organization, design, and baseline characteristics.  J Urban Health. 2004;81(2):301-31015136663PubMedGoogle ScholarCrossref
Lukanova A, Soderberg S, Kaaks R, Jellum E, Stattin P. Serum adiponectin is not associated with risk of colorectal cancer.  Cancer Epidemiol Biomarkers Prev. 2006;15(2):401-40216492937PubMedGoogle ScholarCrossref
Pollak MN, Schernhammer ES, Hankinson SE. Insulin-like growth factors and neoplasia.  Nat Rev Cancer. 2004;4(7):505-51815229476PubMedGoogle ScholarCrossref
Moschos SJ, Mantzoros CS. The role of the IGF system in cancer: from basic to clinical studies and clinical applications.  Oncology. 2002;63(4):317-33212417786PubMedGoogle ScholarCrossref
Ma J, Pollak M, Giovannucci E,  et al.  A prospective study of plasma levels of insulin-like growth factor I (IGF-I) and IGF-binding protein-3, and colorectal cancer risk among men.  Growth Horm IGF Res. 2000;10:(suppl A)  S28-S2910984282PubMedGoogle ScholarCrossref
Manousos O, Souglakos J, Bosetti C,  et al.  IGF-I and IGF-II in relation to colorectal cancer.  Int J Cancer. 1999;83(1):15-1710449601PubMedGoogle ScholarCrossref
Pischon T, Pai JK, Manson JE,  et al.  Single nucleotide polymorphisms at the adiponectin locus and risk of coronary heart disease in men and women.  Obesity (Silver Spring). 2007;15(8):2051-206017712123PubMedGoogle ScholarCrossref
Kaklamani VG, Sadim M, Hsi A,  et al.  Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk.  Cancer Res. 2008;68(9):3178-318418451143PubMedGoogle ScholarCrossref
Laken SJ, Petersen GM, Gruber SB,  et al.  Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC.  Nat Genet. 1997;17(1):79-839288102PubMedGoogle ScholarCrossref
Original Contribution
October 1, 2008

Variants of the Adiponectin (ADIPOQ) and Adiponectin Receptor 1 (ADIPOR1) Genes and Colorectal Cancer Risk

Author Affiliations

Author Affiliations: Cancer Genetics Program, Division of Hematology and Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Drs Kaklamani, Wisinski, and Pasche, and Mss Sadim and Gulden); Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (Mr Do and Dr Mantzoros); Clinical Genetics Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (Dr Offit); Departments of Medicine and Community and Community and Family Medicine, Dartmouth Medical School, Hanover, New Hampshire (Dr Baron); and Department of Health Studies, Medicine, and Human Genetics, University of Chicago, Chicago, Illinois (Dr Ahsan). Dr Pasche is now with the Division of Hematology/Oncology and Comprehensive Cancer Center, University of Alabama, Birmingham.

JAMA. 2008;300(13):1523-1531. doi:10.1001/jama.300.13.1523

Context Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and colorectal cancer risk. Adiponectin is a hormone secreted by the adipose tissue, and serum levels are inversely correlated with obesity and hyperinsulinemia. While there is evidence of an association between circulating adiponectin levels and colorectal cancer risk, no association between genes of the adiponectin pathway and colorectal cancer have been reported to date.

Objective To determine the association of 10 haplotype-tagging single-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancer risk.

Design, Setting, and Patients Two case-control studies including patients with a diagnosis of colorectal cancer and controls were recruited between 2000 and 2007. Case-control study 1 included a total of 441 patients with a diagnosis of colorectal cancer and 658 controls; both groups were of Ashkenazi Jewish ancestry and from New York, New York. Case-control study 2 included 199 patients with a diagnosis of colorectal cancer and 199 controls from Chicago, Illinois, matched 1:1 for sex, age, and ethnicity.

Main Outcome Measures ADIPOQ and ADIPOR1 SNP frequency among cases and controls.

Results In study 1, after adjustment for age, sex, and SNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP were associated with colorectal cancer risk: rs266729 (adjusted odds ratio [AOR], 0.72; 95% confidence interval [CI], 0.55-0.95) and rs822396 (AOR, 0.37; 95% CI, 0.14-1.00) were associated with decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09-2.84) and rs1342387 (AOR, 1.79; 95% CI, 1.18-2.72) were associated with increased risk. In study 2, after adjustment for age, sex, race, and SNPs from the same gene, the ADIPOQ SNP rs266729 was associated with a decreased colorectal cancer risk of similar magnitude as in study 1 (AOR, 0.52; 95% CI, 0.34-0.78). Combined analysis of both studies shows an association of rs266729 with decreased colorectal cancer risk (AOR, 0.73; 95% CI, 0.53-0.99).

Conclusion The SNP rs266729, which tags the 5′ flanking region of the ADIPOQ gene, is associated with decreased colorectal cancer risk.