Aims: The relationship between common haplotype-tagging polymorphisms (rs266729 [11365C>G], rs822395 [−4034A>C], rs822396 [−3964A>G], rs2241766 [45T>G], and rs1501299 [276G>T]) in the ADIPOQ gene and cancer risk has been investigated in different ethnic groups; however, these studies have yielded contradictory results. With this in mind, this meta-analysis was performed in an attempt to draw a more precise conclusion regarding the association between ADIPOQ polymorphisms and cancer risk. Results: In this study, with a total of 19 eligible articles consisting of 52 studies, the pooled odds ratios (ORs) for the association between ADIPOQ rs1501299 and cancer risk were statistically significant (dominant model, TT/GT vs. GG, OR=0.84, 95% confidence interval [CI]: 0.77-0.92; homozygous model, TT vs. GG, OR=0.80, 95% CI: 0.68-0.94). These results suggested that ADIPOQ rs1501299 might be a protection-associated polymorphism in cancer. The stratified analyses indicated that the variant T allele of ADIPOQ rs1501299 was associated with decreased risk of cancer in both Caucasian and Asian populations when compared with the G allele. No significant association for the rest of the polymorphisms was observed under any genetic model. Conclusions: This meta-analysis suggests that the ADIPOQ rs1501299 may be a protective factor for carcinogenesis.
Get full access to this article
View all access options for this article.
References
1.
Al-HarithyRN, Al-ZahraniMH (2012) The adiponectin gene, ADIPOQ, and genetic susceptibility to colon cancer. Oncol Lett, 3:176-180.
2.
Al KhaldiRM, Al MullaF, Al AwadhiS, et al. (2011) Associations of single nucleotide polymorphisms in the adiponectin gene with adiponectin levels and cardio-metabolic risk factors in patients with cancer. Dis Markers, 30:197-212.
3.
AndersonGL, NeuhouserML (2012) Obesity and the risk for premenopausal and postmenopausal breast cancer. Cancer Prev Res (Phila), 5:515-521.
4.
BaldingDJ (2006) A tutorial on statistical methods for population association studies. Nat Rev Genet, 7:781-791.
5.
Beebe-DimmerJL, ZuhlkeKA, RayAM, et al. (2010) Genetic variation in adiponectin (ADIPOQ) and the type 1 receptor (ADIPOR1), obesity and prostate cancer in African Americans. Prostate Cancer Prostatic Dis, 13:362-368.
6.
CalleEE, RodriguezC, Walker-ThurmondK, et al. (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults. N Engl J Med, 348:1625-1638.
7.
Carvajal-CarmonaLG, SpainS, KerrD, et al. (2009) Common variation at the adiponectin locus is not associated with colorectal cancer risk in the UK. Hum Mol Genet, 18:1889-1892.
8.
CuiE, DengA, WangX, et al. (2011) The role of adiponectin (ADIPOQ) gene polymorphisms in the susceptibility and prognosis of non-small cell lung cancer. Biochem Cell Biol, 89:308-313.
9.
Demark-WahnefriedW, PlatzEA, LigibelJA, et al. (2012) The role of obesity in cancer survival and recurrence. Cancer Epidemiol Biomarkers Prev, 21:1244-1259.
10.
DhillonPK, PenneyKL, SchumacherF, et al. (2011) Common polymorphisms in the adiponectin and its receptor genes, adiponectin levels and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev, 20:2618-2627.
11.
DoeckeJD, ZhaoZZ, StarkMS, et al. (2008) Single nucleotide polymorphisms in obesity-related genes and the risk of esophageal cancers. Cancer Epidemiol Biomarkers Prev, 17:1007-1012.
12.
EckelRH, GrundySM, ZimmetPZ (2005) The metabolic syndrome. Lancet, 365:1415-1428.
13.
EggerM, DaveySG, SchneiderM, et al. (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ, 315:629-634.
14.
El-ZeinM, ParentME, RousseauMC (2013) Comments on a recent meta-analysis: obesity and lung cancer. Int J Cancer, 132:1962-1963.
15.
FanHJ, WenZF, XuBL, et al. (2013) Three adiponectin rs1501299G/T, rs822395A/C, and rs822396A/G polymorphisms and risk of cancer development: a meta-analysis. Tumour Biol, 34:769-778.
16.
GrossmannME, NkhataKJ, MizunoNK, et al. (2008) Effects of adiponectin on breast cancer cell growth and signaling. Br J Cancer, 98:370-379.
17.
HalaasJL, GajiwalaKS, MaffeiM, et al. (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science, 269:543-546.
18.
HeB, PanY, ZhangY, et al. (2011) Effects of genetic variations in the adiponectin pathway genes on the risk of colorectal cancer in the Chinese population. BMC Med Genet, 12:94
19.
HigginsJ, ThompsonS, DeeksJ, et al. (2002) Statistical heterogeneity in systematic reviews of clinical trials: a critical appraisal of guidelines and practice. J Health Serv Res Policy, 7:51-61.
20.
HivertMF, ManningAK, McAteerJB, et al. (2008) Common variants in the adiponectin gene (ADIPOQ) associated with plasma adiponectin levels, type 2 diabetes, and diabetes-related quantitative traits: the Framingham Offspring Study. Diabetes, 57:3353-3359.
21.
HottaK, FunahashiT, AritaY, et al. (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol, 20:1595-1599.
22.
HuE, LiangP, SpiegelmanBM (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem, 271:10697-10703.
23.
IsomaaB, AlmgrenP, TuomiT, et al. (2001) Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care, 24:683-689.
24.
KaklamaniV, YiN, ZhangK, et al. (2011) Polymorphisms of ADIPOQ and ADIPOR1 and prostate cancer risk. Metab Clin Exp, 60:1234-1243.
25.
KaklamaniVG, SadimM, HsiA, et al. (2008a) Variants of the adiponectin and adiponectin receptor 1 genes and breast cancer risk. Cancer Res, 68:3178-3184.
26.
KaklamaniVG, WisinskiKB, SadimM, et al. (2008b) Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. JAMA, 300:1523-1531.
27.
KekuTO, VidalA, OliverS, et al. (2012) Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites. Cancer Causes Control, 23:1127-1138.
28.
KyriakouT, CollinsLJ, Spencer-JonesNJ, et al. (2008) Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity. J Hum Genet, 53:718-727.
29.
LingH, WaterworthDM, StirnadelHA, et al. (2009) Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study. Obesity (Silver Spring), 17:737-744.
30.
LiuL, ZhongR, WeiS, et al. (2011) Interactions between genetic variants in the adiponectin, adiponectin receptor 1 and environmental factors on the risk of colorectal cancer. PLoS One, 6:e27301
31.
MokdadAH, FordES, BowmanBA, et al. (2003) Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. J Am Med Assoc, 289:76-79.
32.
MooreSC, LeitzmannMF, AlbanesD, et al. (2009) Adipokine genes and prostate cancer risk. Int J Cancer, 124:869-876.
33.
NaSY, MyungSJ (2012) [Obesity and colorectal cancer]. Korean J Gastroenterol, 59:16-26.
34.
NkhataKJ, RayA, SchusterTF, et al. (2009) Effects of adiponectin and leptin co-treatment on human breast cancer cell growth. Oncol Rep, 21:1611-1619.
35.
Partida-PerezM, de la LuzAM, Peregrina-SandovalJ, et al. (2010) Association of LEP and ADIPOQ common variants with colorectal cancer in Mexican patients. Cancer Biomark, 7:117-121.
36.
PechlivanisS, BermejoJL, PardiniB, et al. (2009) Genetic variation in adipokine genes and risk of colorectal cancer. Eur J Endocrinol, 160:933-940.
37.
RibeiroR, MonteiroC, CatalanV, et al. (2012) Obesity and prostate cancer: gene expression signature of human periprostatic adipose tissue. BMC Med, 10:108
38.
SchmidCH, StarkPC, BerlinJA, et al. (2004) Meta-regression detected associations between heterogeneous treatment effects and study-level, but not patient-level, factors. J Clin Epidemiol, 57:683-697.
39.
TangH, DongX, HassanM, et al. (2011) Body mass index and obesity- and diabetes-associated genotypes and risk for pancreatic cancer. Cancer Epidemiol Biomarkers Prev, 20:779-792.
40.
TarabraE, ActisGC, FaddaM, et al. (2012) The obesity gene and colorectal cancer risk: a population study in Northern Italy. Eur J Intern Med, 23:65-69.
41.
TerasLR, GoodmanM, PatelAV, et al. (2009) No association between polymorphisms in LEP, LEPR, ADIPOQ, ADIPOR1, or ADIPOR2 and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev, 18:2553-2557.
42.
TsilidisKK, HelzlsouerKJ, SmithMW, et al. (2009) Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer. Cancer Causes Control, 20:1739-1751.
43.
WangMH, HelzlsouerKJ, SmithMW, et al. (2009) Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II. Prostate, 69:874-885.
44.
WeyerC, FunahashiT, TanakaS, et al. (2001) Hypoadiponectinemia in obesity and type 2 diabetes: Close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab, 86:1930-1935.
45.
WolkA, GridleyG, SvenssonM, et al. (2001) A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control, 12:13-21.
46.
XuY, HeB, PanY, et al. (2013) The roles of ADIPOQ genetic variations in cancer risk: evidence from published studies. Mol Biol Rep, 40:1135-1144.
47.
YamauchiT, KamonJ, WakiH, et al. (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med, 7:941-946.
48.
YiN, KaklamaniVG, PascheB (2011) Bayesian analysis of genetic interactions in case-control studies, with application to adiponectin genes and colorectal cancer risk. Ann Hum Genet, 75:90-104.
49.
ZhouW, LiuY, ZhongDW (2013) Adiponectin (ADIPOQ) rs2241766 G/T polymorphism is associated with risk of cancer: evidence from a meta-analysis. Tumour Biol, 34:493-504.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
