Four hundred twenty patients with colorectal cancer and five hundred fifty and five healthy controls were evaluated in this population-based case-control association study, and there were no statistically significant differences in their demographic data and clinical characteristics as summarized in Table .
Demographic and clinical characteristics of CRC patients and the controls
The genotype distribution of the polymorphisms of ADIPOQ and ADIPOR1 between the cases and controls are presented in Table . The observed frequencies of all tested genotypes and alleles in controls did not derivate from the Hardy-Weinberg equilibrium. Logistic regression analysis revealed a significantly decreased risk (adjusted OR, 0.53; 95% CI: 0.35-0.81) for the rs12733285 C/T heterozygote when compared with the rs12733285 C/C wild-type homozygote as shown in Table . Similarly, carriers of the A allele (rs1342387 A/G or A/A) had decreased risk (adjusted OR 0.59; 95% CI: 0.45-0.78, and adjusted OR 0.59; 95% CI: 0.39-0.89, respectively) for CRC compared with noncarriers (i.e., rs1342387 G/G) as shown in Table , suggesting that carriers of the rs1342387 A allele had a significantly decreased risk for colorectal cancer (adjusted OR 0.59; 95% CI: 0.46-0.77). In contrast, the distribution of the five polymorphisms (rs266729, rs822395, rs822396, rs1501766 and rs1501299) in ADIPOQ was not statistically significantly different between the case and control groups as shown in Table .
The genotype distribution of ADIPOQ and ADIPOR1 in CRC patients and controls
Subgroup analysis was performed based on the tumor site in this study, and logistic regression analysis revealed a significantly increased risk for the rs266729G/C heterozygote (adjusted OR, 1.50; 95% CI: 1.05-2.14) as compared with the rs266729 C/C wild-type homozygote as shown in Table , suggesting that carriers of the 266729 G allele had a significantly increased risk for colorectal cancer (adjusted OR 1.45; 95% CI: 1.03-2.05). However, there was no difference in the genotype distribution between the sub-cohort of colon cancer and rectal cancer.
Genotype distribution in relation to sub sites in colorectal cancer
Through the population-based case-control study of 420 CRC patients and 555 age-and gender- matched healthy controls in the Chinese population, we observed that CRC patients had lower frequency of rs2733285C/T and rs1342387A/G or A/A than healthy controls, and that carriers of the rs2733285T and rs1342387A allele had a significantly decreased risk for developing CRC. Moreover, we also revealed that rs266729G/C genotype and rs266729G allele was a risk factor for colon cancer.
It has been well known that obesity is one of the major risks for CRC [31
] and that lack of physical exercise, diets with high sugar, refined grains, and low fiber are all believed as the risks of CRC [33
]. Adiponectin is secreted by adipose tissue, and epidemic studies have demonstrated that its plasma levels were inversely correlated to BMI [37
]. Recent studies have shown that polymorphism in ADIPOQ
(rs2241766) is associated with the risk of breast cancer [27
], and that a polymorphism rs266729 is associated with the risk of colorectal cancer [28
]. However, in this case-control study, we failed to replicate the association between the two positive variants at ADIPOQ
(rs2241766, and rs266729) and CRC risk in Chinese population. Our findings are consistent with the studies reported in Czech [30
] and British populations[39
]. However, our subgroup analysis still revealed that rs266729 G/C and 266729 G allele were risk factors for colon cancer but not for rectal cancer. These findings may partly explain the previous contradictive studies on the association between the polymorphism of rs2241766 and CRC risk [28
]. Moreover, basic research had also predicted that ADIPOQ
have more potential effects on colon cancer than on rectal cancer [40
], indicating that rs266729 G/C and 266729 G allele were risk factors for colon cancer but not for rectal cancer, several studies have confirmed that polymorphisms rs266729 C/C, rs1501299 T/T and rs2241766 G/G in the ADIPOQ
were associated with adiponectin plasma levels [20
]. In particularly, such association were also deduced in Chinese population that G allele of rs266729 was significantly associated with lower adiponectin plasma levels[41
], and that low levels of adiponectin was associated with the increased risk of CRC [13
The association between adiponectin type 1 receptor level and the two polymorphisms (rs12733285, rs1342387) in ADIPOR
was still unclear. In this case-control study, the association between polymorphisms in ADIPOR1
(rs12733285, rs1342387) and CRC risk has also been investigated, and the results indicate that individuals with rs12733285C/T or rs1342387A/G or A/A had a decreased risk of CRC, which was similar with the finding in North American populations [28
]. However, we have not observed the rs12733285T/T genotype both in case and control groups, in a sharp contrast with 15% of the rs12733285T/T genotype in North American population [27
]. Nevertheless, our results are consistent with Hap-Map data among western Asian population http://www.hapmap.org/index.html.en
. For polymorphism (rs1342387) of ADIPOR1
, the distribution of genotypes in our studies was similar to the results by Wang et al [43
]. Previous clinical studies have shown that the genotypes rs1342387A/G or A/A were associated with higher adiponectin plasma levels [21
], and G/G genotype of rs1342387 of the ADIPOR1
gene was also associated with the indicators of obesity [44
]. Therefore, the reason of the G/G genotype of rs1342387 as a risk factor for CRC may be correlated to obesity and insulin resistance. In addition, clinical studies have also revealed that adiponectin type 1 receptor is related to colorectal cancer progression[46
]. However, the function of rs1342387 in ADIPOR1
remains unclear, and the direct relationship between rs1342387 and the risk of CRC needs to be further evaluated.