The roles of ADIPOQ genetic variations in cancer risk: evidence from published studies

Adiponectin produced by adipose tissue, which is involved in complex diseases related to obesity, such as cancer. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. However, epidemiological results were inconsistent. To examine this controversy, we assessed reported studies of association between ADIPOQ polymorphisms and cancer risk. Relevant studies were selected by PUBMED, EMBASE update to January 12th, 2012. According to the acceptance and exclusion criteria, 15 studies involved three polymorphisms (rs266729, rs2241766, rs1501299) of ADIPOQ were included. Summary odds ratio (ORs) and 95 % confidence intervals (CIs) were calculated using random-effect or fixed-effect models based on the heterogeneity of included studies. A total of 15 case–control studies related rs266729 (5,615 cases and 6,425 controls), rs2241766 (5,318 cases and 6,118 controls) and rs1501299 (3,751 cases and 5,104 controls) were included to analyze the ADIPOQ polymorphisms and cancer risk. For rs1501299, T allele was associated with decreased cancer risk. In addition, cancer type subgroup analysis revealed T allele was associated with decreased colorectal and prostate cancer risk. Ethnicity subgroup analysis observed a decreased risk in both Asian and Caucasian descendents. As to rs2241766, a borderline decreased cancer risk was observed. This meta-analysis indicated T allele of rs1501299 was an obvious protection factor for cancer risk, and G allele of rs2241766 was a potential protection factor for cancer risk, especially in Caucasian descendents. Further studies should be performed to clarify the roles of ADIPOQ polymorphisms in the cancer risk.     

Novel functional variants locus in PLCE1 and susceptibility to esophageal squamous cell carcinoma: Based on published genome-wide association studies in a central Chinese population

A novel functional single nucleotide polymorphism (SNP) rs2274223 located in the phospholipase C epsilon 1 (PLCE1) gene was found to be associated with the risk of esophageal squamous cell carcinoma (ESCC) by three large-scale genome-wide association studies (GWAS) in Chinese populations. In the present study, we validated this finding and also explored the risk of ESCC associated with other two unreported potentially functional SNPs (rs17417407 G > T and rs2274224 C > G) of PLCE1 in a population-based case–control study to investigate the association between these three potentially functional SNPs in PLCE1 and susceptibility to ESCC. A total of 381 ESCC cases and 420 controls matched by age and sex were recruited and successfully genotyped for three SNPs (rs17417407, rs2274223 and rs2274224) of the PLCE1 in a central Chinese population. SNP rs2274223 was independently associated with increased risk of ESCC (adjusted odds ratio [OR], 2.80; 95% confidence interval [95% CI], 1.45–5.39 for GG vs. AA), and SNP rs2274224 was found to be associated with decreased risk of ESCC (adjusted OR, 0.65; 95% CI, 0.46–0.91 for CG vs. CC). The combined effects of risk alleles for three SNPs (rs17417407T, rs2274223G and rs2274224G) were found to be associated with elevated risk of ESCC in a dose-dependent effect manner (P_trend = 0.005). The G_rs17417407A_rs2274223C_rs2274224 haplotype decreased the risk of ESCC (adjusted OR, 0.76; 95% CI, 0.62–0.93), meanwhile the G_rs17417407G_rs2274223C_rs2274224 and T_rs17417407G_rs2274223C_rs2274224 haplotypes could increase the risk of ESCC (adjusted OR, 1.75; 95% CI, 1.33–2.18 and OR, 2.51; 95% CI, 1.15–2.49). Gene–environment interaction analysis presented a best model consisted of four factors (rs2274223, rs2274224, family history, and smoking) with testing balance accuracy (TBA): 0.66 and cross validation consistency (CVC): 7/10, which could increase the esophageal cancer risk in the “high risk group” with 3.67-fold (OR: 3.67, 95% CI: 2.74–4.92), compared to the “low risk group”. Our results further confirmed that genetic variations in PLCE1 may contribute to ESCC risk associated with tobacco exposure in a central Chinese population. Further functional studies are needed to validate our results.     

Case-control study of rhinoconjunctivitis associated with IL5RA polymorphisms in Japanese women: The Kyushu Okinawa Maternal and Child Health Study

BackgroundEpidemiological research on the relationship between single nucleotide polymorphisms (SNPs) in the IL5RA gene and allergic disorders is limited. We examined the relationship between IL5RA SNPs and risk of rhinoconjunctivitis in young adult Japanese women.MethodsIncluded were 393 women who met the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC) for rhinoconjunctivitis. Controls were 767 women without rhinoconjunctivitis according to the ISAAC criteria who had not been diagnosed with allergic rhinitis by a doctor. Adjustment was made for age, region of residence, presence of older siblings, smoking, and education.ResultsCompared with the CC genotype of SNP rs6771148, the CG genotype, but not the GG genotype, was significantly associated with a reduced risk of rhinoconjunctivitis: the adjusted OR for the CG genotype was 0.76 (95% CI: 0.58–0.99). No evident associations were found between SNPs rs17882210, rs3804797, rs334809, rs9831572, or rs17881144 and rhinoconjunctivitis. The ACTAGA haplotype of rs17882210, rs3804797, rs334809, rs9831572, rs6771148, and rs17881144 was significantly inversely associated with rhinoconjunctivitis (crude OR = 0.58, 95% CI: 0.37–0.88) while the GTAGCA haplotype was significantly positively related to rhinoconjunctivitis (crude OR = 1.74, 95% CI: 1.14–2.65). No significant interactions affecting rhinoconjunctivitis were observed between any of the six SNPs and smoking.ConclusionThis is the first study to show significant associations between IL5RA SNP rs6771148, the ACTAGA haplotype, and the GTAGCA haplotype and the risk of rhinoconjunctivitis. We did not find evidence for interactions affecting rhinoconjunctivitis between any of the IL5RA SNPs and smoking.     

Genetic Variations in ADIPOQ Gene Are Associated with Chronic Obstructive Pulmonary Disease

Background

Adiponectin is reported to be related to the development of chronic obstructive pulmonary disease (COPD). Genetic variants in the gene encoding adiponectin (ADIPOQ) have been reported to be associated with adiponectin level in several genome–wide linkage and association studies. However, relatively little is known about the effects of ADIPOQ gene variants on COPD susceptibility. We determined the frequencies of single-nucleotide polymorphisms (SNPs) in ADIPOQ in a Chinese Han population and their possible association with COPD susceptibility.

Methods

We conducted a case–control study of 279 COPD patients and 367 age- and gender-distribution-matched control subjects. Seven tagging SNPs in ADIPOQ, including rs710445, rs16861205, rs822396, rs7627128, rs1501299, rs3821799 and rs1063537 were genotyped by SNaPshot. Association analysis of genotypes/alleles and haplotypes constructed from these loci with COPD was conducted under different genetic models.

Results

The alleles or genotypes of rs1501299 distributed significantly differently in COPD patients and controls (allele: P = 0.002, OR = 1.43 and 95%CI = 1.14–1.79; genotype: P = 0.008). The allele A at rs1501299 was potentially associated with an increased risk of COPD in all dominant model analysis (P = 0.009; OR: 1.54; 95%CI: 1.11–2.13), recessive model analyses (P = 0.015; OR: 1.75; 95% CI: 1.11–2.75) and additive model analyses (P = 0.003; OR: 2.11; 95% CI: 1.29–3.47). In haplotype analysis, we observed haplotypes AAAAACT and GGACCTC had protective effects, while haplotypes AGAACTC, AGGCCTC, GGAACTC, GGACACT and GGGCCTC were significantly associated with the increased risk of COPD.

Conclusions

We conducted the first investigation of the association between the SNPs in ADIPOQ and COPD risk. Our current findings suggest that ADIPOQ may be a potential risk gene for COPD. Further studies in larger groups are warranted to confirm our results.     

Gene Polymorphisms of ADIPOQ +45T>G,UCP2 -866G>A,and FABP2 Ala54Thr on the Risk of Colorectal Cancer: A Matched Case-Control Study

As insulin resistance (IR) is an established risk factor for colorectal cancer (CRC), we explored the association between each of the IR-related gene polymorphisms of adiponectin (ADIPOQ) rs2241766, uncoupling protein 2 (UCP2) rs659366, and fatty acid-binding protein (FABP2) rs1799883 and CRC risk. Genotyping of blood samples and collection of lifestyle and dietary habits were performed for 400 case-control pairs. Unconditional logistic regression (ULR) was applied to assess the effects of the three single nucleotide polymorphisms (SNP), environmental factors. Both ULR and generalized multifactor dimensionality reduction (GMDR) were used to test the gene-gene and gene-environment interactions on CRC risk. Subjects carrying the ADIPOQ rs2241766 TG+GG genotype had a higher CRC risk than those carrying the TT genotype (OR = 1.429, 95% CI 1.069–1.909). The additive and multiplicative interactions between ADIPOQ rs2241766 and FABP2 rs1799883 on CRC were found by ULR (RERI = 0.764, 95%CI 0.218∼1.311, AP = 0.514, 95%CI 0.165∼0.864, S = −1.745, 95%CI is unachievable, and P_multi = 0.017, respectively). Furthermore, the high order gene-gene interaction of the three SNPs were found by GMDR (P = 0.0107). A significant dosage effect with an increasing number of risk genotypes was observed as the risk of CRC increased (P_trend = 0.037). In GMDR, the gene-environment interaction among the three SNPs and red meat consumption on CRC risk was significant (P = 0.0107). Compared with subjects with low red meat consumption and null risk genotypes, those with high-red meat consumption and three risk genotypes had 3.439-fold CRC risk (95% CI 1.410–8.385). In conclusion, the results showed that the ADIPOQ rs2241766 TG+GG genotype increased CRC risk. Given the complexity of the carcinogen for CRC, ADIPOQ rs2241766, UCP2 rs659366, FABP2 rs1799883 and red meat consumption potentially worked together in affecting CRC risk.     

HapMap-based study identifies risk sub-region on chromosome 19q13.3 in relation to lung cancer among Chinese

Background: Chromosome 19q13.3 has been identified as one of the regions that associate with cancer risk in previous studies. Methods: We systematically examined the 70.772 kb region comprising four genes on chromosome 19q13.3 among Chinese using the haplotype-tagging SNP (htSNP) approach and the HapMap platform. The study involved 339 lung cancer cases and 358 non-cancer controls. Two htSNPs (rs1046282 and rs735482) captured most of the common haplotypes of CD3EA and the combined effects of sixteen htSNPs provided high coverage of common haplotypes of ERCC2, PPP1R13L, CD3EAP and ERCC1. Results: Both carriers of variant CC genotype [adjusted OR (95% CI) = 1.28 (1.02–1.60), P = 0.04] and variant C-allele among >20 years’ smokers [OR (95% CI) = 2.13 (1.24–3.67), P = 0.006] for CD3EAP rs735482 were at increased risk of lung cancer. Four haplotype blocks of strong linkage disequilibrium were identified. The haplotype ERCC2 rs3916874^G and rs238415^C [OR (95% CI) = 1.26 (1.02–1.57), P = 0.03] in block 1 and the haplotype PPP1R13L rs4803817^A, CD3EAP rs1046282^T, rs735482^C, ERCC1 rs3212980^A, rs3212964^G [OR (95% CI) = 3.56 (1.55–8.18), P = 0.005] in block 3 were associated with lung cancer risk. MDR (multifactor dimensionality reduction) analysis demonstrated the best significant model of two-attributes containing smoking duration and rs2298881 in ERCC1 (P = 0.004–0.005) and suggested that the effects of high-order interactions among smoking duration and ERCC2, PPP1R13, ERCC1 htSNPs could modulate lung cancer risk. Conclusions: HapMap-based study of 19q13.3 identified that genetic variation of CD3EAP and two loci were associated with lung cancer risk and interaction of smoking duration and genetic variants was the strongest predictor of lung cancer risk in a Chinese population.     

Effects of <Emphasis Type="Italic">ADIPOQ</Emphasis> polymorphisms on PCOS risk: a meta-analysis

Background

Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.

Methods

Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p?=?0.02, OR?=?0.77, 95%CI 0.62–0.95; allele model: p?=?0.001, OR?=?1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.

Conclusions

Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.

     

Polymorphisms of tumor-related genes IL-10, PSCA,MTRR and NOC3L are associated with the risk of gastric cancer in the Chinese Han population

BackgroundGastric cancer is the fourth most common cancer in the world. Environmental and genetic factors both play critical roles in the etiology of gastric cancer. Hundreds of SNPs have been identified to have association with the risk of gastric cancer in many races. In this study, 25 SNPs in genes for IL-10, IL-1B, MTRR, TNF-а, PSCA, PLCE1 and NOC3L were analyzed to further evaluate their associations with gastric cancer susceptibility in the Chinese Han population.MethodsTwo hundred and seventy nine gastric cancer patients and 296 healthy controls were recruited in this study. SNP genotyping was conducted using Sequenom MassARRAY RS1000. Data management and statistical analyses were conducted by Sequenom Typer 4.0 Software and Pearson's χ² test.ResultsOne protective allele and three risk alleles for gastric cancer patients were found in this study. The allele “G” of rs1801394 in MTRR showed an association with a decreased risk of gastric cancer: odds ratio (OR) = 0.74, 95% confidence interval (95% CI) = 0.57–0.97, P = 0.030 in the additive model; OR = 0.495, 95% CI = 0.26–0.95, P = 0.034 in the recessive model. The other three SNPs, the allele “C” of rs1800871 in IL10 (OR = 1.33, 95% CI = 1.04–1.90; P = 0.026 in the additive model; OR = 1.46, 95% CI = 1.04–2.06; P = 0.030 in the recessive model), the allele “A” of rs2976391 in PSCA (OR = 1.30, 95% CI = 1.01–1.66; P = 0.041 in the additive model and OR = 1.48, 95% CI = 1.04–2.11, P = 0.028 in the recessive model), and the allele “G” of rs17109928 in NOC3L gene (OR = 1.34, 95% CI = 1.01–1.78; P = 0.042 by additive model analysis; OR = 1.47, 95% CI = 1.04–2.07, P = 0.028 by dominant model analysis), showed an association with an increased risk of gastric cancer.ConclusionsThese results indicate the importance of four gastric cancer susceptibility polymorphisms of IL-10, NOC3L, PSCA and MTRR in the Chinese Han population, which could be used in the determination of gastric cancer risk in clinical practice.     

Association of Genetic Variants in the Adiponectin Gene with Metabolic Syndrome: A Case-Control Study and a Systematic Meta-Analysis in the Chinese Population

Background

The prevalence of metabolic syndrome has been rising worldwide, including in China, but knowledge on specific genetic determinants of metabolic syndrome is very limited. A number of studies have reported that polymorphisms in the ADIPOQ gene are associated with metabolic syndrome in Chinese Han populations. However, data is still conflicting. The objective of this study was to examine the associations of the adiponectin genetic variants with metabolic syndrome by a case-control study and meta-analyses in Chinese.

Methods

We first investigated the association of ADIPOQ rs2241766 (+45T>G in exon 2), rs266729 (−11377C>G in promoter) and rs1501299 (+276G>T in intron 2) polymorphisms with metabolic syndrome in a Hubei Han Chinese population with 322 metabolic syndrome patients and 161 normal controls recruited from the Yichang, Hubei. Then we comprehensively reviewed the association between ADIPOQ rs2241766/rs266729/rs1501299 and metabolic syndrome in the Chinese populations via a meta-analysis. The strength of association was assessed by odds ratios (ORs) with 95% confidence intervals (CI).

Results

The G allele frequency of rs2241766 in metabolic syndrome patients was significantly higher than those of controls group (29.8% vs 23.3%, OR = 1.40, P = 0.033). The logistic regression analysis adjusted by gender and age showed a nominally significant association for rs2241766 GG+GT genotype (P = 0.065, OR = 1.55) and rs1501299 GG genotype in recessive model (OR = 1.54, P = 0.066). However, no association was observed for rs266729 in our sample. We identified thirteen studies for rs2241766 (2,684 metabolic syndrome patients and 2,864 controls), three studies for rs266729, and eleven studies for rs1501299 (2,889 metabolic syndrome patients and 3,304 controls) in Chinese. Meta-analysis indicated significant associations for the rs2241766 G allele (OR = 1.14, 95%CI = 1.05–1.24, P = 0.003), rs266729 GG+GT genotypes (OR = 0.80, 95%CI = 0.68–0.92, P = 0.003) and rs1501299 GG+TG genotypes (OR = 1.42, 95%CI 1.16–1.75, P = 0.001).

Conclusions

Our results demonstrated ADIPOQ as a pleiotropic locus for metabolic syndrome and its components in the Han Chinese population.     

Genetic polymorphisms involved in the inflammatory response and lung cancer risk: A case-control study in Japan

Evidence is accumulating that chronic inflammation may have an important mechanism for the development and progression of lung cancer. Therefore, genetic polymorphisms in genes that involved in the inflammatory response may be associated with lung cancer risk. We evaluated the role of tumor necrosis factor α (TNFA) rs1799724, interleukin 1β (IL1B) rs16944, IL6 rs1800796, myeloperoxidase (MPO) rs2333227 and C-reactive protein (CRP) rs2794520 in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). CRP rs2794520 (OR = 1.64, 95% CI = 1.19–2.26) and IL6 rs1800796 (OR = 1.41, 95% CI = 1.02–1.96) were associated with lung cancer risk. In addition, we assessed interactions between the polymorphisms and smoking. The polymorphisms did not significantly modify the association between smoking and lung cancer. As TNFA triggers a cytokine cascade, the modifying effect of the TNFA rs1799724 genotypes on the association of any of the remaining polymorphisms with lung cancer risk was also examined. There was a significant interaction between TNFA rs1799724 and MPO rs2333227 (P_interaction = 0.058). Future studies involving larger control and case populations will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the inflammation pathway in lung cancer.     

Genetic variation in a miR-335 binding site in BIRC5 alters susceptibility to lung cancer in Chinese Han populations

Polymorphisms in 3′ untranslated region (UTR) of cancer-related genes might affect their regulation by microRNAs (miRNAs) and thereby contribute to carcinogenesis. In this study, we screened single nucleotide polymorphisms (SNPs) in 3′ UTR of cancer-related genes and investigated their effects on risk of lung cancer. First, we genotyped seven SNPs in a Chinese Han population with 600 lung cancer patients and 600 matched healthy controls and found that compared with the TT genotype of rs2239680 in 3′ UTR of baculoviral IAP repeat containing 5 (BIRC5), C allele was associated with a significantly increased risk of lung cancer and advanced pathologic stage, with the odds ratio for participants carrying the CT or CC genotype being 1.50 [95% confidence interval (CI) 1.20–1.89, P < 0.01] and 2.29 (95% CI 1.64–3.18, P < 0.01), respectively. These results were further replicated and confirmed in another independent population with 1000 lung cancer cases and 1000 matched healthy controls. In support of the postulation that the 3′ UTR SNP may directly affect miRNA-binding site, reporter gene assays indicated BIRC5 was a direct target of miR-335, and the rs2239680 T > C change resulted in altered regulation of BIRC5 expression. Moreover, BIRC5 was over expressed in lung cancer tissues compared with the normal lung tissues, and the protein levels of BIRC5 correlated with SNP genotypes in normal lung tissues. Our findings defined a 3′ UTR SNP in human BIRC5 oncogene that may increase individual susceptibility to lung cancer probably by attenuating the interaction between miR-335 and BIRC5.     

ERCC1 haplotypes modify bladder cancer risk: A case–control study

Bladder cancer risk is highly influenced by environmental and/or predisposing genetic factors. In the last decades growing evidence of the major role played by DNA repair systems in the developing of bladder cancer has been provided. To better investigate the involvement of DNA repair genes previously reported to be significantly associated with bladder cancer risk, we examined in a case–control study (456 cases and 376 hospital controls) 36 single nucleotide polymorphisms (SNPs) in 10 DNA repair genes, through a better gene coverage and a deep investigation of the haplotype role. A single SNP analysis showed a significantly increased risk given by XRCC1-rs915927 G allele (OR = 1.55, CI 95% 1.02–2.37 for dominant model) and a protective effect of the rare alleles of 3 ERCC1 SNPs: rs967591 (OR = 0.66, CI 95% 0.46–0.95), rs735482 (OR = 0.62, CI 95% 0.42–0.90) and rs2336219 (OR = 0.63, CI 95% 0.43–0.93). Haplotype analysis revealed that cases had a statistically significant excess of XRCC3-TAGT and ERCC1-GAT haplotypes, whereas ERCC1-AAC, MGMT-TA, XRCC1-TGCC and ERCC2-TGAA haplotypes were significantly underrepresented. Together with other published data on large case–control studies, our findings provide epidemiological evidence supporting a link between DNA repair gene variants and bladder cancer development, and suggest that the effects of high-order interactions should be taken into account as modulating factors affecting bladder cancer risk. A detailed characterization of DNA repair genetic variation is warranted and might ultimately help to identify multiple susceptibility variants that could be responsible for joint effects on the risk.     

Genetic polymorphisms in AURKA,BRCA1, CCNE1 and CDK2 are associated with ovarian cancer susceptibility among Chinese Han women

IntroductionCentrosome aberrations and cell-cycle deregulation have important implications for ovarian cancer development. The AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation.MethodsUsing a haplotype-based analysis, this study aimed to investigate whether genetic polymorphisms in these four genes may contribute to ovarian cancer susceptibility. A total of 22 single nucleotide polymorphisms (SNPs) in these four genes were genotyped in 287 cases of ovarian serous cystadenocarcinomas and 618 age-matched cancer-free controls from the Chinese Han population, and then haplotype blocks were reconstructed according to our genotyping data and linkage disequilibrium (LD) status of these SNPs.ResultsFor AURKA, we found that haplotype GA [rs6064391 (T→G) + rs911162 (G→A)] was strongly associated with decreased ovarian cancer risk (adjusted OR = 0.31, 95% CI = 0.15–0.63, P = 0.0012). For BRCA1, we found that haplotype CGTAG was associated with decreased ovarian cancer risk (adjusted OR = 0.64, 95% CI = 0.41–0.98, P = 0.0417). Moreover, women harboring homozygous GA/CGTAG haplotypes showed the lowest risk (OR = 0.12, 95% CI = 0.02–0.94, P = 0.0438). In CCNE1, the SNPs rs3218035 and rs3218042 were significantly associated with increased ovarian cancer risk (rs3218035: adjusted OR = 5.20, 95% CI = 1.85–14.52, P = 0.0017; rs3218042: adjusted OR = 4.98, 95% CI = 1.75–14.19, P = 0.0027). For CDK2, no significant association was found.ConclusionsThis study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may affect ovarian cancer susceptibility in Chinese Han women.     

A common variant in the adiponectin gene and polycystic ovary syndrome risk

In this study, we explored whether polymorphisms in insulin receptor (INSR), adiponectin (ADIPOQ), parathyroid hormone (PTH), and vitamin D receptor (VDR) genes are associated with polycystic ovary syndrome (PCOS). A total of 362 subjects, including 181 women with PCOS and 181 controls were enrolled in this case-control study. Two SNPs (rs2059806 and rs1799817) in the INSR gene, two SNPs (rs2241766 and rs1501299) in the ADIPOQ gene, one SNP (rs6256) in the PTH gene, and one SNP (rs757343) in the VDR gene were analyzed using PCR-RFLP method. We observed no significant difference in genotype and allele frequencies between the women with PCOS and controls for the rs2059806, rs1799817, rs1501299, rs6256, and rs757343 polymorphisms either before or after adjustment for confounding factors including age and BMI. However, the ADIPOQ rs2241766 “TT” genotype compared with “TG and GG” genotypes was associated with a 1.93-fold increased risk for PCOS (P = 0.006, OR = 1.93, 95% CI = 1.20–3.11), and the differences remained significant after adjustment for age and BMI (P = 0.039, OR = 1.72, 95% CI = 1.03–2.86). Furthermore, the ADIPOQ rs2241766 “T” allele was significantly overrepresented in women with PCOS than controls (P = 0.006; OR = 1.80, 95% CI = 1.18–2.70), and the difference remained significant after Bonferroni correction. Our findings suggest that the ADIPOQ rs2241766 “TT” genotype is a marker of increased PCOS susceptibility. This study also indicates for the first time that there are no significant association between INSR rs2059806, PTH rs6256, and VDR rs757343 gene polymorphisms and PCOS risk. However, these data remain to be confirmed in larger studies and in other populations.     

Association of TP53 codon 72 and CDH1 genetic polymorphisms with colorectal cancer risk in Bangladeshi population

Till now no pharmacogenetic study of TP53 codon 72 (Arg72Pro) and CDH1 rs16260 (-160C<A) genes has been reported on Bangladeshi population relating those with colorectal cancer. So the aim of the study is to determine whether there is an elevated risk of colorectal cancer development with TP53 codon 72 and CDH1 rs16260 genetic polymorphism in Bangladeshi population for the first time. To investigate the association of these two SNPs, we conducted a case-control study with 288 colorectal cancer patients and 295 healthy volunteers by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. We found an increased risk of association between Arg/Pro heterozygosity (adjusted OR = 2.58, 95% CI = 1.77–3.77, p < 0.05) and Pro/Pro mutant homozygosity (adjusted OR = 2.92, 95% CI = 1.78–4.78, p < 0.05) along with the combined genotype (Arg/Pro + Pro/Pro) (adjusted OR = 2.70, 95% CI = 1.90–3.82, p < 0.05) and colorectal cancer predisposition. In case of CDH1 rs16260 polymorphism, C/A heterozygous and A/A mutant homozygous are significantly (p < 0.05) found to be associated with colorectal cancer risk with adjusted OR of 1.94 and 2.63, respectively. The combined genotype of C/A and A/A was also found to be strongly associated with colorectal cancer risk compared to C/C genotype (adjusted OR = 2.02, 95% CI = 1.42–2.87, p < 0.05). In conclusion, heterozygosity and mutant homozygosity as well as the combination of both TP53 Arg72Pro and CDH1 rs16260 polymorphisms are responsible to increase the risk of colorectal cancer development in Bangladeshi population.     

Effects of polymorphisms in translesion DNA synthesis genes on lung cancer risk and prognosis in Chinese men

PurposeTranslesion DNA synthesis (TLS) plays an important role in promoting replication through DNA lesions. Genetic polymorphisms in TLS genes may have potential roles in lung cancer development in humans.MethodsWe evaluated the association between genetic variants in six TLS genes and the risk and survival of lung cancer in a case–control study in China. Included in the study are 224 lung cancer patients and 448 healthy controls.ResultsCarriers of the G allele of POLκ rs5744724 had significantly reduced risk of lung cancer (odds ratio (OR) = 0.62, 95% confidence interval (CI): 0.44–0.89), comparing with those carrying the C allele, and the AA genotype of PCNA rs25406 was also associated with significantly decreased cancer risk compared with the major homozygote alleles (OR = 0.47, 95% CI: 0.25–0.86). Haplotype analysis showed that subjects with the POLκ C-G (rs5744533–rs5744724) haplotype had decreased risk of lung cancer (OR = 0.69, 95% CI: 0.49–0.98), comparing with those carrying the C-C haplotype. Besides, the heterozygote of REV1 rs3087386 and rs3792136 were independent prognostic factors for lung cancer survival with hazard radio (HR) 1.54 (95% CI: 1.12–2.12) and 1.44 (95% CI: 1.06–1.97) respectively.ConclusionsOur findings suggested that genetic variants in POLκ and PCNA genes may play roles in the susceptibility of lung cancer, and REV1 gene may have roles in lung cancer survival in Chinese men.     

Selected polymorphisms of GSTP1 and TERT were associated with glioma risk in Han Chinese

Background: Current evidence suggests that a majority of the inherited risks play a major role in glioma susceptibility, and glioma is due to the co-inheritance of multiple low-risk variants. These variants can be identified through association studies including such as genome-wide association studies (GWAS), which has led the glioma epidemiology researchers to focus on identifying potential disease-causing factors. Methods: We evaluated and validated 10 tag single nucleotide polymorphisms (tSNPs) in seven genes associated with glioma susceptibility in a Han Chinese population, including 301 glioma cases and 302 controls, using a multiplexed single nucleotide polymorphism (SNP) MassEXTEND assay. We ascertained the genotypic frequencies for each tSNP in control subjects were within Hardy–Weinberg equilibrium (HWE) using an exact test, and then compared the genotype and allele frequencies of glioma patients and control subjects using the χ2 test. We then applied three genetic models (dominant, recessive, and additive) using PLINK software to assess the association of each tSNP with glioma risk. Results: We identified two tSNPs to be associated with glioma susceptibility (rs1695, GSTP1, P = 0.019; rs2853676, TERT, P = 0.039), which we confirmed using dominant and additive model analyses. The genotype &ldquo;GA&rdquo; for rs1695 was recognized to be a protective genotype for glioma (OR, 0.67; 95% CI, 0.47–0.96; P = 0.027), while the genotype &ldquo;AG&rdquo; for rs2853676 was shown to be a risk genotype for glioma (OR, 1.50; 95% CI, 1.05–2.15; P = 0.025). Conclusion: Our results, and those from previous studies, suggest potential genetic contributes for GSTP1 and TERT in glioma development.