Adiponectin is a protein hormone secreted exclusively by adipocytes and it is responsible for insulin sensitization in the human body. Deregulation of adiponectin and its downstream signaling pathway genes have been found to be involved in the gastric cancer carcinogenesis; however, whether the variants on adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) affect the prognosis of gastric cancer patients are still unknown. Here we have recruited 455 gastric cancer patients, who have received the gastrectomy treatment to evaluate the prognostic effects of variants on ADIPOQ (rs266729 and rs822395) and AdipoR1 (rs12733285 and rs1342387) for the gastric cancer patients. No significant association between the four variants and the overall survival of the gastric cancer patients was found. However, for those patients without a previous history of alcohol drinking, the rs266729 GG/CG genotype carriers showed a significantly decreased gastric cancer mortality compared to homogeneity CC patients (HR 0.74, 95 % CI 0.56-0.97; p = 0.032) after adjustment for variants age, sex, smoking status, tumor stage, tumor location and post-surgery chemotherapy. No significant association between the variant rs266729 genotypes and overall survival for the gastric cancer patients with an alcohol drinking habit. These data suggested that the variant rs266729 was an independent prognostic factor for the never drinking gastric cancer patients who received surgical treatment.

BACKGROUND:Epidemiological studies have suggested that variants on adiponectin (ADIPOQ) and its receptor ADIPOR1 (adiponectin receptor 1) are associated with colorectal cancer (CRC) risk; however, the results were inconclusive. The aim of the study was to evaluate the associations between the variants on ADIPOQ and ADIPOR1 and the CRC risk with a hospital-based case-control study in the Chinese population along with meta-analysis of available epidemiological studies.METHODS:With a hospital-based case-control study of 341 cases and 727 controls, the associations between the common variants on ADIPOQ (rs266729, rs822395, rs2241766 and rs1501299) and ADIPOR1 (rs1342387 and rs12733285) and CRC susceptibility were evaluated. Meta-analysis of the published epidemiological studies was performed to investigate the associations between the variants and CRC risk.RESULTS:For the population study, we found that variant rs1342387 of ADIPOR1 was associated with a reduced risk for CRC [adjusted odds ratio (OR) = 0.74, 95% confidential intervals (95% CI) = 0.57-0.97; CT/TT vs. CC]. The meta-analysis also suggested a significant association for rs1342387 and CRC risk; the pooled OR was 0.79 (95% CI = 0.66-0.95) for the CT/TT carriers compared to CC homozygotes under the random-effects model (Q = 8.06, df = 4, P = 0.089; I(2) = 50.4%). The case-control study found no significant association for variants rs266729, rs822395, rs2241766, and rs1501299 on ADIPOQ or variant rs12733285 on ADIPOR1 and CRC susceptibility, which were consistent with results from the meta-analysis studies.CONCLUSIONS:These data suggested that variant rs1342387 on ADIPOR1 may be a novel CRC susceptibility factor.

The vitamin D receptor (VDR) principally mediates the anticancer activities of vitamin D. Various epidemiological studies have investigated the associations of VDR gene polymorphisms with ovarian cancer; however, the results have been inconclusive. In the current study, we evaluated, in a meta-analysis, the association of five common single nucleotide polymorphisms (SNPs) in the VDR gene (ApaI, BsmI, Cdx-2, FokI, and TaqI) with the risk of ovarian cancer. Six eligible studies, with a total of 4,107 cases and 6,661 controls, which evaluated the association of these variants and ovarian cancer risk, were identified from the MEDLINE and PubMed databases. The meta-analysis indicated that FokI was associated with an increased ovarian cancer risk, with a pooled odds ratio (OR) of 1.10 [95% confidence intervals (95% CI) = 1.00-1.20] for CT heterozygotes and 1.16 (95% CI = 1.02-1.30) for TT homozygotes relative to common CC carriers. Carriers of the T allele (also known as the f allele) showed an 11% (pooled OR = 1.11, 95% CI = 1.02-1.21; TT/CT vs. CC) increased risk of ovarian cancer relative to CC carriers. For FokI, no significant heterogeneity between the studies was found (I-2 = 0%, P = 0.62 for the Q test). There was no statistically significant association between the other four variants (ApaI, BsmI, Cdx-2 and TaqI) and risk of ovarian cancer. These data indicate that the polymorphism FokI on the VDR is a susceptibility factor for ovarian cancer. Nevertheless, more studies are warranted to elucidate the underlying mechanisms of the VDR in development of ovarian cancer.

Folate is essential for DNA synthesis and methylation and implicated in the process of carcinogenesis. Several studies inconclusively suggested increased folate intake may reduce ovarian cancer risk. Studies concerning the association between C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR), an important enzyme in folate metabolism, and ovarian cancer risk also resulted in no agreement. The meta-analysis was conducted based on current studies to assess the association between folate intake, the MTHFR C667T polymorphism and ovarian cancer risk. 1,158 cases out of 217,309 participants from four cohort studies, 4,519 cases and 6,031 controls from four case–control studies about folate intake along with 5,617 cases and 9,808 controls from 10 publications concerning the polymorphism were pooled, respectively. We detected no significant association between total folate (RR = 1.04, 95 % confidence interval (CI) = 0.87–1.23) or dietary folate (RR = 0.88, 95 % CI = 0.75–1.05) intake and ovarian cancer risk, and also no significant relationship was found between MTHFR C677T polymorphism and ovarian cancer risk (TT vs. CC: odds ratio (OR) = 1.15, 95 % CI = 0.90–1.46; CT vs. CC: OR = 1.04, 95 % CI = 0.94–1.16). Our analysis indicated neither folate intake nor MTHFR C677T polymorphism is related to altered susceptibility of ovarian cancer.

Experimental data suggest a protective effect of vitamin D on breast cancer; however, epidemiologic results remain inclusive. With a Chinese population-based case-control study and meta-analysis of the observational studies, we here systematically evaluated the association of blood 25(OH) D level and breast cancer risk. With 593 breast cancer cases and 580 cancer-free controls from Shanghai, China, we found that 80% of the normal women had severe vitamin D deficiency (less than 20 ng/mL) and 15.2% had mild deficiency (20 to 30 ng/mL) and only 4.8% of women had sufficient vitamin D level (>30 ng/mL) while the proportion was 96.1%, 3.2% and 0.7% respectively for the breast cancer patients. Compared to those with the lowest quartile of plasma 25(OH) D level, women with highest quartile 25(OH) D level showed a significant decreased breast cancer risk (Q4 vs. Q1: OR = 0.10, 95% CI = 0.06-0.15) and every 1 ng/ml increment of plasma 25(OH) D level led to a 16% lower odds of breast cancer (OR = 0.84, 95% CI = 0.81-0.87; P, 0.001). From the meta-analysis of the observational studies, we found that women with highest quantile of blood 25(OH) D level was associated with a significantly reduced breast cancer risk compared to those with lowest quantile of blood 25(OH) D level for the 11 nested case-control and retrospective studies (pooled OR = 0.86, 95% CI = 0.75-1.00) and 10 case-control studies (7 population based, OR = 0.35, 95% CI = 0.24-0.52; 3 hospital based, OR = 0.08, 95% CI = 0.02-0.33). These results suggest that vitamin D may have a chemo-preventive effect against breast cancer.

Abstract Vitamin D plays an important role in metabolism, cellular function and reproduction. Vitamin D has also been suggested to have potential protective effects against many cancers including breast cancer; however, the data from the epidemiological studies have been inconclusive. Our previous meta-analysis have found high dietary vitamin D intake significantly decreased breast cancer risk (RR = 0.91, 95% CI = 0.85-0.97) and women with higher circulating 25(OH)D level showed about 45% (95% CI = 0.38-0.80) decrease in breast cancer risk (Breast Cancer Res Treat. 2010;121(2):469-77). In a population-based case control study with 593 cases and 580 controls from Shanghai area, we have found that 80% of the normal women with severe vitamin D deficiency (less than 20ng/mL), 15.2% were of deficiency status (20 to 30ng/mL). Only 4.8% of women had sufficient vitamin D level (> 30ng/mL). However, in the breast cancer patients, nearly 96.1% were of vitamin D severe deficiency, 3.2% were of vitamin D deficiency and only 0.7% had sufficient levels. Based on a logistic regression analysis, compared to those with the lowest quintile of plasma 25(OH)D level, women with higher level had significant lower breast risk (Q2 vs. Q1, OR = 0.45, 95% CI = 0.33-0.63; Q3 vs. Q1, OR = 0.25, 95% CI = 0.17-0.36; Q4 vs.Q1, OR = 0.09, 95% CI = 0.06-0.15) showing a significant dose-effect relationship (p-trend < 0.001) after adjusted for the co-variants. We also found a seasonal distribution of vitamin D. Significantly lower vitamin D levels were found for the cases and controls in spring and summer (p < 0.01). In the controls the mean level of vitamin D was higher in the summer (17.76ng/ml) and autumn (16.25ng/ml), and lower in the spring (15.67ng/ml) and winter (10.75ng/ml). However, in the breast cancer patients, the plasma level of vitamin D was highest in the autumn (14.38ng/ml) and lowest in the spring (10.16ng/ml). These results provide a strong evidence that vitamin D may have a chemo-preventive effect against breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 643. doi:1538-7445.AM2012-643