Combined analysis of the association between p73 G4C14-to-A4T14 polymorphisms and cancer risk

P73 is a structural and functional homologue of p53, and plays an important role in regulating cell cycle and apoptosis. A potentially functional polymorphism (designated as p73 G4C14-to-A4T14) has been identified in a region in exon 2 of the p73 gene, which may theoretically form a stem-loop structure and thereby affect p73 expression. Several investigations have reported the correlation between p73 G4C14-to-A4T14 polymorphism and cancer risk. However, the results are inconclusive. To further assess the association between p73 polymorphism and cancer risk, we performed meta-analysis of the data sets obtained from 26 individual studies involving 8,148 cancer patients and 8,150 controls. The association between p73 G4C14-to-A4T14 polymorphism and cancer risk was determined by crude odd ratios (OR) with 95% CI (confidential interval). AT-allele carriers were found to have a significantly increased risk of cervical cancer (AT/GC vs. GC/GC, OR = 1.63, 95% CI = 1.14–2.33; AT/AT + AT/GC vs. GC/GC, OR = 1.49, 95% CI = 1.05–2.10), colorectal cancer (AT/AT vs. AT/GC + GC/GC, OR = 1.98, 95% CI = 1.25–3.12), head and neck cancer (AT/AT + AT/GC vs. GC/GC, OR = 1.44, 95% CI = 1.06–1.96) and other cancers (AT/AT vs. GC/GC, OR = 1.78, 95% CI = 1.24–2.57; AT/AT vs. AT/GC + GC/GC, OR = 1.80, 95% CI = 1.26–2.56). In the stratified analysis of ethnicity, a significantly elevated cancer risk was found in Caucasians (AT/AT + AT/GC vs. GC/GC, OR = 1.18, 95% CI = 1.08–1.30; allele AT vs. allele GC, OR = 1.15, 95% CI = 1.06–1.24). No significant association of p73 polymorphism with the cancer risk of smoking was detected by stratified analysis by smoking status. Together, our data suggest that the p73 G4C14-to-A4T14 may be a risk factor of cancer especially in Caucasians.     

Association analysis of p16 (CDKN2A) and RB1 polymorphisms with susceptibility to cervical cancer in Indian population

The potent tumor suppressors P16 and RB1 are the key regulators of cell cycle machinery in eukaryotes. Polymorphisms in these genes play an important role in the outcome of various diseases including cancer. In the present study, we evaluated the association of p16 and RB1 polymorphisms with cervical cancer susceptibility in Indian population. We screened 150 histologically confirmed cervical cancer cases along with equal number of healthy controls with normal cervical cytology. PCR-RFLP method was employed for genotyping of SNPs in p16 C540G (rs11515), C580T (rs3088440) in the 3′-UTR of exon 3 and RB1 A153104G (rs4151580) located in the intron 18 and confirmed by direct sequencing. Both patients and controls were screened for HPV infection. In this case–control study 84.67% (127/150) of cases were found to be positive for HPV DNA sequence. Women carrying p16 C540G carrier genotypes 540 (CG/GG) may have protective effect for the development of cervical cancer (P = 0.0001, OR = 0.31, 95% CI = 0.17–0.56). And SNP at C580T of p16 gene was found to be negatively associated with the risk of cervical cancer (P = 0.0004, OR = 0.04, 95% CI = 0.002–0.63). p16 (540C/580T) has emerged as a major risk haplotype (P = 0.033, OR = 1.47, 95% CI = 1.05–2.07) whereas p16 (540G/580T) as a chief protective haplotype (P = 0.014, OR = 0.39, 95% CI = 0.18–0.83) for the development of cervical cancer among Indian women. Contrary to this, SNP at A153104G of RB1 gene showed statistically significant association (P = 0.035, OR = 1.69, 95% CI = 1.06–2.68) with increased susceptibility for the development of cervical cancer. Our results suggest that single nucleotide polymorphisms in p16, RB1 genes may affect the susceptibility to cervical cancer collectively.     

Association of IL-10-1082 promoter polymorphism with susceptibility to gastric cancer: evidence from 22 case–control studies

Evidence suggested that interleukin-10 (IL-10) may be involved in the etiology of gastric cancer (GC). However, epidemiological studies on the association between IL-10-1082 promoter polymorphism and GC risk are still ambiguous. To quantitatively summarize the evidence for such a relationship, we performed a meta-analysis. Systemic searches of the PubMed and Medline databases were performed, with the last report up to July 2011. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. 22 independent studies including 4,289 cases and 5,965 controls were involved in this meta-analysis. Obvious association was found when all studies were pooled into the meta-analysis (A vs. G: OR = 0.489, 95% CI = 0.335–0.713, P < 0.001). In the subgroup analysis by ethnicity, we observed significant associations in Asians (A vs. G: OR = 0.651, 95% CI = 0.506–0.838, P = 0.001; AA vs. GG: OR = 0.482, 95% CI = 0.328–0.709, P < 0.001; AA/AG vs. GG: OR = 0.711, 95% CI = 0.527–0.959, P = 0.025; AA vs. AG/GG: OR = 0.701, 95% CI = 0.520–0.944, P = 0.019) and Caucasians (A vs. G: OR = 0.365, 95% CI = 0.140–0.949, P = 0.039), but not in Latino population. When stratified analysis by control sources, our results indicated that A allele decreased approximately 48% risk among population-based studies (A vs. G: OR = 0.524, 95% CI = 0.374–0.733, P < 0.001). Taken together, this meta-analysis suggests that IL-10-1082 polymorphism is associated with GC risk.     

<Emphasis Type="Italic">TGFBR1</Emphasis>*6A/9A polymorphism and cancer risk: a meta-analysis of 13,662 cases and 14,147 controls

Published data on the association between TGFBR1*6A/9A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 32 studies including 13,662 cases and 14,147 controls were involved in this meta-analysis. Overall, significantly elevated cancer risks were associated with TGFBR1*6A in all genetic models (for allelic effect: OR = 1.11; 95% CI = 1.03–1.21; for 6A/6A vs. 9A/9A: OR = 1.30; 95% CI = 1.01–1.69; for 9A/6A vs. 9A/9A: OR = 1.08; 95% CI = 1.01–1.15; for dominant model: OR = 1.08; 95% CI = 1.02–1.15; for recessive model: OR = 1.29; 95% CI = 1.00–1.68). In the subgroup analysis by cancer types, significant associations were found in breast cancer (for allelic effect: OR = 1.16; 95% CI = 1.01–1.34) and ovarian cancer (for allelic effect: OR = 1.24; 95% CI = 1.00–1.54; for 6A/6A vs. 9A/9A: OR = 2.34; 95% CI = 1.03–5.33). However, no significant associations were found in colorectal cancer, bladder cancer, prostate cancer and lung cancer for all genetic models. In summary, this meta-analysis suggests that the TGFBR1*6A/9A polymorphism is associated with cancer susceptibility, increasing the risk of breast and ovarian cancer.     

<Emphasis Type="Italic">FAS</Emphasis> −1,377 G/A polymorphism is associated with cancer susceptibility: evidence from 10,564 cases and 12,075 controls

Published data on the association between FAS −1,377 G/A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 studies including 10,564 cases and 12,075 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with AA variant genotype when all the eligible studies were pooled into the meta-analysis (for AA vs GG: OR = 1.19; 95% CI = 1.01–1.40; P _{heterogeneity} = 0.05; for recessive model: OR = 1.21; 95% CI = 1.04–1.41; P _{heterogeneity} = 0.05). In the subgroup analysis by ethnicity, borderline statistically significantly increased risks were found among Asians for recessive model (OR = 1.20; 95% CI = 1.00–1.45; P _{heterogeneity} = 0.01). In the subgroup analysis by population-based controls or hospital-based controls, statistically significantly increased risks were found among groups with population-based controls for AA versus GG (OR = 1.27; 95% CI = 1.02–1.58; P _{heterogeneity} = 0.05) and recessive model (OR = 1.25; 95% CI = 1.00–1.59; P _{heterogeneity} = 0.01). For breast cancer, borderline statistically significantly increased risks were found for AA versus GG (OR = 1.29; 95% CI = 1.00–1.67; P _{heterogeneity} = 0.41). In summary, this meta-analysis suggests that the FAS −1,377 G/A polymorphism is associated with cancer susceptibility. L. X. Qiu, J. Shi and H. Yuan contributed equally to this work and should be considered as co-first authors.     

Contribution of the IBD5 locus to inflammatory bowel disease: a meta-analysis

To evaluate the association of the IBD5 locus to the predisposition of inflammatory bowel diseases (IBDs), a series of meta-analyses between five IBD5 variants (OCTN1 C1672T, OCTN2 G-207C, OCTN1/2 TC haplotype, IGR2096a_1, IGR2198a_1 and IGR2230a_1) and Crohn’s disease (CD) and ulcerative colitis (UC) were performed, which included a total of 26 studies. Overall, five IBD5 variants in a per-allele model of inheritance were significantly associated with elevated CD risk (for OCTN1: OR = 1.23, 95% CI = 1.16–1.30, P < 0.001; for OCTN2: OR = 1.20, 95% CI = 1.11–1.30, P < 0.001; for IGR2096a_1: OR = 1.36, 95% CI = 1.24–1.46, P < 0.001; for IGR2198a_1: OR = 1.34, 95% CI = 1.24–1.46, P < 0.001; for IGR2230a_1: OR = 1.35, 95% CI = 1.23–1.48, P < 0.001) and OCTN1/2 TC haplotype (OR = 1.32, 95% CI = 1.22–1.43, P < 0.001). In the subgroup analysis, the statistically significant associations were also observed in adult- and pediatric-onset CD and in Caucasians for five IBD5 variants and the OCTN1/2 TC haplotype. A statistically significant increase in the risk of UC was detected in a recessive model of inheritances for OCTN1 (OR = 1.23, 95% CI = 1.08–1.40, P < 0.001), OCTN2 (OR = 1.18, 95% CI = 1.05–1.33, P = 0.006), IGR2096a_1 (OR = 1.37, 95% CI = 1.15–1.62, P < 0.001) and IGR2198a_1 (OR = 1.35, 95% CI = 1.10–1.66, P = 0.004); the increased risks of UC were maintained in the adult and Caucasian subgroups, but not the pediatric subgroup. In summary, our results suggested that the IBD5 locus contributes to the susceptibility of CD in a per-allele manner in adults, children and Caucasians, and the locus contributes to the susceptibility of UC in a recessive manner in adult and Caucasian populations.     

Association between ATM 5557G>A polymorphism and breast cancer risk: a meta-analysis

Epidemiological studies have evaluated the association between ATM 5557G>A (p.D1853N) polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of nine studies included 3155 cases and 2752 controls were identified. When all nine studies were pooled into the meta-analysis, there was no evidence for significant association between 5557G>A mutation and breast cancer risk(for G/A vs. G/G: OR = 1.05, 95% CI = 0.83–1.34; for A/A vs. G/G: OR = 0.77, 95% CI = 0.58–1.03; for dominant model: OR = 1.04, 95% CI = 0.82–1.31; for recessive model: OR = 0.87, 95% CI = 0.69–1.09). In the subgroup analyses by family history and ethnicity, significant associations were found among Amerindians (for G/A vs. G/G: OR = 2.19, 95% CI = 1.38–3.47; for dominant model: OR = 2.15, 95% CI = 1.37–3.38). In summary, the meta-analysis suggest that ATM 5557G>A polymorphism is associated with increased breast cancer risk among Amerindians. However, due to the small subjects included in analysis and the selection bias existed in some studies, the results for Amerindians should be interpreted with caution.     

Meta-analysis of TYK2 gene polymorphisms association with susceptibility to autoimmune and inflammatory diseases

The aim of our meta-analysis was to quantitatively summarize the association of TYK2 gene polymorphisms with autoimmune and inflammatory diseases. 11 studies that included data from 21497 cases and 22647 controls were identified. OR was used as a measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for six TYK2 gene polymorphisms (rs34536443, rs2304256, rs280523, rs280519, rs12720270 and rs12720356). Significant association was found in rs34536443 (C versus G: OR = 0.76, 95% CI = 0.69–0.84, P < 0.00001; GC + CC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0005; CC versus GG + GC: OR = 0.76, 95% CI = 0.28–2.05, P = 0.58; CC versus GG: OR = 0.74, 95% CI = 0.27–2.02, P = 0.56; GC versus GG: OR = 0.78, 95% CI = 0.68–0.90, P = 0.0006) and rs2304256 (A versus C: OR = 0.78, 95% CI = 0.70–0.87, P < 0.0001; CA + AA versus CC: OR = 0.69, 95% CI = 0.59–0.81, P < 0.0001; AA versus CC + CA: OR = 0.75, 95% CI = 0.66–1.00, P = 0.05; AA versus CC: OR = 0.64, 95% CI = 0.47–0.86, P = 0.003; CA versus CC: OR = 0.70, 95% CI = 0.60–0.83, P < 0.0001) in TYK2 gene, but not for the other polymorphisms (rs280523, rs280519, rs12720270, and rs12720356). This meta-analysis demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms, but not rs280523, rs280519, rs12720270 and rs12720356.     

The Ku70 ?1310C/G promoter polymorphism is associated with breast cancer susceptibility in Chinese Han population

Ku70 plays an important role in the DSBR (DNA double-strand breaks repair) and maintenance of genomic integrity. Genetic variations within human Ku70 have been demonstrated to be associated with increased risk of several types of cancers. In this hospital-based case–control study, we aimed to investigate whether a single nucleotide polymorphism (SNP) in the promoter region (rs2267437) of Ku70 gene is associated with susceptibility to breast cancer in Chinese Han population. A total of 293 patients with breast cancer and 301 age-matched healthy controls were enrolled in this study. The Ku70 −1310C/G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) analysis. A significant difference in genotype distribution and allele frequency was observed between patients and controls. The CG or GG carries were at higher risk of breast cancer compared with the CC homozygotes (OR = 1.43, 95% CI = 1.02–2.00, P = 0.038 and OR = 3.53, 95% CI = 1.60–7.80, P = 0.002, respectively). Further stratification analysis revealed that G allele was associated with an increased risk of breast cancer among premenopausal women (OR = 1.68, 95% CI = 1.21–2.33, P = 0.002), but not in postmenopausal women (OR = 1.33, 5% CI = 0.85–2.10, P = 0.216). Our study suggests that the Ku70 −1310C/G promoter polymorphism may be a susceptibility factor for breast cancer in Chinese Han population.     

The association between the mannose-binding lectin codon 54 polymorphism and systemic lupus erythematosus: a meta-analysis update

The aim of this study was to determine whether the functional mannose-binding lectin (MBL2) exon 1 codon 54 polymorphism (rs1800450) confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted on the MBL2 codon 54 polymorphism across 21 comparative studies. Meta-analysis showed an association between the MBL2 codon 54 B allele and SLE in all study subjects [odds ratio (OR) = 1.298, 95% confidence interval (CI) = 1.154–1.459, P = 1.4 × 10⁻⁵]. Analysis after stratification by ethnicity indicated that the MBL2 codon 54 B allele is significantly associated with SLE in Europeans, Asian, and Africans (OR = 1.246, 95% CI = 1.062–1.462, P = 0.007; OR = 1.268, 95% CI = 1.049–1.532, P = 0.014; OR = 1.939, 95% CI = 1.269–2.962, P = 0.002, respectively). However, African Americans had a much lower prevalence of the T allele (5.8%) than any other populations studied, whereas Asians had the highest prevalence (16.2%). This meta-analysis confirms that the MBL2 codon 54 polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent.     

Association of 1347 G/A cytochrome P450 4F2 (CYP4F2) gene variant with hypertension and stroke

Genetic variants of cytochrome P450 4F2 (CYP4F2) gene have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case–control study we investigated the association of 1347 G/A polymorphism (rs2108622) in the 11th exon region of CYP4F2 gene with hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Five hundred and seven stroke patients (hypertensives: normotensives = 279:228) and four hundred and eighty seven, age and sex matched controls (males: females = 356:131) (hypertensives: normotensives = 148:339) were involved in the study. The genotypes were determined by PCR-RFLP technique. Genotypes were confirmed by subjecting the PCR products to sequencing. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. AA genotype and A allele associated significantly with stroke and hypertension [P = 0.009; OR = 1.59 (95% CI = 1.119–2.283) and P = 0.010; OR = 1.26 (95% CI = 1.056–1.502); P = 0.01; OR = 1.58 (95% CI = 1.11–2.272) and P = 0.010; OR = 1.25(95% CI = 1.054–1.504) respectively]. A stepwise logistic regression analysis confirmed these findings. To establish that this polymorphism is associated with stroke independent of hypertension; we compared stroke patients without hypertension with normotensive controls. Significant difference was observed in genotypic distribution and allelic frequency between the two groups (P = 0.001 and 0.002 respectively). Evaluating the association of this polymorphism with stroke subtypes we found significant associations with cardioembolic stroke (P < 0.001). In conclusion our study suggests that 1347A allele of CYP4F2 gene is an important risk factor for hypertension and ischemic stroke.     

Quantitative assessment of the effect of MTHFR polymorphisms on the risk of lung carcinoma

Published studies on the relationships between 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and lung cancer risk have been conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between MTHFR C677T and A1298C polymorphisms and lung cancer risk. A total of 15 studies including 10,753 cases and 11,275 controls described C677T genotypes, among which 11 articles totalling 6,161 cases and 7,684 controls described A1298C genotypes, were also involved in this meta-analysis. Overall, no significantly elevated lung cancer risk was found in any genetic models when all studies were pooled. For C677T polymorphism: (TT vs. CC: OR = 1.17, 95% CI = 0.97–1.42; TC vs. CC: OR = 1.06, 95% CI = 0.94–1.20; dominant model: OR = 1.09, 95% CI = 0.96–1.24; and recessive model: OR = 1.08, 95% CI = 0.95–1.24); for A1298C polymorphism: (CC vs. AA: OR = 1.04, 95% CI = 0.91–1.19; AC vs. AA: OR = 0.98, 95% CI = 0.91–1.06; dominant model: OR = 0.99, 95% CI = 0.92–1.06; and recessive model: OR = 1.05, 95% CI = 0.92–1.20). In the subgroup analyses, the results showed that 677T varients could decrease lung cancer risk in female (OR = 0.63, 95% CI = 0.41–0.95, P-value = 0.03, 677CC as reference). No evidence of any associations of MTHFR A1298C polymorphism with lung cancer was found in overall or subgroup analyses. Our meta-analysis supports that the common polymorphisms of C677T and A1298C in MTHFR gene are not susceptibility gene for lung cancer from currently available evidence.     

XPA A23G polymorphism and susceptibility to cancer: a meta-analysis

Xeroderma pigmentosum group A (XPA) participates in modulating recognition of DNA damage during the DNA nucleotide excision repair process. The XPA A23G polymorphism has been investigated in case–control studies to evaluate the cancer risk attributed to the variant, but the results were conflicting. To clarify the effect of XPA A23G polymorphism in cancer risk, we conducted a meta-analysis that included 30 published case–control studies. Overall, no significant association of XPA A23G variant with cancer susceptibility was observed for any genetic model. However, significant association was observed for colorectal cancer (GG vs. AA: OR = 1.68, 95% CI = 1.15–2.44; dominant genetic model GG + AG vs. AA: OR = 1.54, 95% CI = 1.08–1.17), for breast cancer an increased but non-significant risk was found (GG vs. AA: OR = 1.27, 95% CI = 0.98–1.66; dominant genetic model GG + AG vs. AA: OR = 1.27, 95% CI = 0.99–1.63), and for head and neck cancer an increased risk was observed in recessive model (OR = 1.19, 95% CI = 1.02–1.38), whereas for lung cancer a significant reduced risk was observed (GG vs. AA: OR = 0.77, 95% CI = 0.66–0.90; dominant genetic model GG + AG vs. AA: OR = 0.76, 95% CI = 0.66–0.87), it’s noting that in Asian population the inverse association was more apparent. In addition, in Asian population for esophageal cancer a significant decreased risk was also found in dominant genetic model (OR = 0.55; 95% CI = 0.43–0.70) and for head and neck cancer an increased risk was observed in dominant genetic model (OR = 1.51, 95% CI = 1.03–2.23). The meta-analysis suggested that the XPA A23G G allele is a low-penetrant risk factor for cancer development.     

Vitamin D receptor ApaI,TaqI, BsmI,and FokI polymorphisms and psoriasis susceptibility: a meta-analysis

The aim of this study was to explore whether vitamin D receptor (VDR) polymorphisms confer susceptibility to psoriasis. Meta-analyses were conducted on the associations between the VDR ApaI, TaqI, BsmI, and FokI polymorphisms and psoriasis. Nine relevant studies on VDR polymorphisms and psoriasis were included in this meta-analysis, which involved 742 psoriasis patients and 715 controls. Meta-analysis indicated an association between the VDR ApaI A allele and psoriasis in Turkish studies (OR = 0.684, 95% CI = 0.475–0.985, p = 0.041). Meta-analysis indicated an association between the BsmI B allele and psoriasis in Asians (OR = 0.636, 95% CI = 0.411–0.984, p = 0.041), and showed a significant association between the FF and ff genotypes of the FokI polymorphism and psoriasis in all study subjects and in Turkish studies (OR = 2.028, 95% CI = 1.194–3.446, p = 0.009; OR = 3.582, 95% CI = 1.602–8.009, p = 0.002). This meta-analysis suggests that the VDR ApaI polymorphism confers susceptibility to psoriasis in the Turkish population. In addition, associations were found between the BsmI polymorphism and susceptibility to psoriasis in Asians and between the Fok I polymorphism and psoriasis in the Turkish population.     

Association of thrombospondin 1 gene with schizophrenia in Korean population

Thrombospondin 1 (THBS1), a multi-domain glycoprotein, is secreted from astrocytes and promotes synaptogenesis. Increasing evidence has suggested that not only various markers for synaptic pathology, but also astrocytes are affected in schizophrenia. In this study, we investigated whether coding region single nucleotide polymorphisms (cSNPs) of the THBS1 gene were associated with schizophrenia and with the clinical symptoms of schizophrenia patients. We genotyped two cSNPs [rs2228261 (Asn470Asn) and rs2292305 (Thr523Ala)] using direct sequencing in 220 schizophrenia patients and 376 control subjects. In this study, rs2228261 revealed significant association with schizophrenia in both codominant (TT vs. CC, P = 0.009, OR = 2.10, 95% CI = 1.23–3.59) and recessive models (TT vs. CC/CT, P = 0.0012, OR = 2.28, 95% CI = 1.38–3.77). Also, rs2292305 was associated with schizophrenia in the recessive model (GG vs. AA/AG, P = 0.0052, OR = 2.05, 95% CI = 1.24–3.38). Additionally, in the analysis of the haplotype, the CA and TG haplotypes consisting of rs2228261 and rs2292305 were associated with schizophrenia in the dominant (P = 0.019, OR = 1.79, 95% CI = 1.10–2.90) and recessive models, respectively (P = 0.0086, OR = 0.51, 95% CI = 0.31–0.84). In further analysis according to the clinical symptoms, rs2292305 showed a weak association with the poor concentration symptoms of schizophrenia patients in the dominant model (AG/GG vs. AA, P = 0.024, OR = 2.04, 95% CI = 1.09–3.83). The results suggest that the THBS1 gene may contribute to the susceptibility of schizophrenia.     

CXCL12 G801A polymorphism and breast cancer risk: a meta-analysis

The G801A polymorphism in the CXCL12 gene has been implicated in breast cancer risk. However, the published findings are inconsistent. We therefore performed a meta-analysis to investigate this relationship. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively. Five published case–control studies, including 1,058 breast cancer cases and 1,023 controls were identified. No study had a deviation from the Hardy–Weinberg equilibrium (HWE) in controls. We found that the CXCL12 G801A (rs1801157) polymorphism was associated with a significantly increased risk of breast cancer risk when all studies were pooled into the meta-analysis (codomiant model: AA versus GG, OR = 1.64, 95% CI = 1.16–2.33; GA versus GG, OR = 1.42, 95% CI = 1.18–1.71; dominant model: AA/GA versus GG, OR = 1.44, 95% CI = 1.21–1.72). Furthermore, Egger’s test did not show any evidence of publication bias (P > 0.05 for the dominant model). In conclusion, the results suggest that the CXCL12 G801A polymorphism may be a low-penetrant risk factor for developing breast cancer.     

Prevalence of the NKG2D Thr72Ala polymorphism in patients with systemic lupus erythematosus

Multiple studies have indicated that SLE incidence exhibits a strong genetic background. We studied the frequency of the natural killer group 2, member D (NKG2D) receptor Thr72Ala (rs2255336) polymorphism in patients with SLE (n = 243) and controls (n = 502) in a sample of the Polish population. The p value for SLE patients with the Thr/Thr genotype was 0.0455 and Odds Ratio (OR) = 0.3846 (95% CI = 0.1458–1.014). For the Thr/Thr and Ala/Thr genotypes we found p = 0.0135 and OR = 0.6556 (95% CI = 0.4684–0.9177). The frequency of the NKG2D 72Thr allele in patients and controls was respectively, 15 and 21%, P = 0.0046, OR = 0.6547 (95% CI = 0.4877–0.8789). Our studies may confirm that the NKG2D 72Thr gene variant may protect against the incidence of SLE.     

Association of p53 codon 72 polymorphism with prostate cancer: a meta-analysis

Relationship of prostate cancer with the polymorphism of p53 codon 72 was reported with inconsistent results. The purpose of this study was to quantitatively evaluate the association between p53 codon 72 polymorphism and prostate cancer susceptibility. We performed an extensive search of relevant studies and made a meta-analysis, including 8 studies with 815 prostate cancer cases and 1047 controls. The combined results showed that there were no significant differences in genotype distribution between prostate cancer cases and control on the basis of all studies, CC/GC versus GG (OR = 1.24, 95% CI: 0.93–1.65), GG/GC versus CC (OR = 0.96, 95% CI: 0.60–1.55), GC versus GG (OR = 1.27, 95% CI: 0.91–1.77), CC versus GG (OR = 1.25, 95% CI:0.74–2.12), GC versus CC (OR = 1.09, 95% CI: 0.63–1.87). When stratifying for the race, there were also no statistically significant differences in genotype distribution between prostate cancer cases and controls. This meta-analysis did not provide an evidence of confirming association between p53 codon 72 polymorphism and prostate cancer.     

Role of tissue plasminogen activator and plasminogen activator inhibitor polymorphism in myocardial infarction

A case–control association study on 229 Myocardial Infarction (MI) patients and 217 healthy controls was carried out to determine the role of tissue-plasminogen activator (t-PA) (Alu-repeat insertion (I)/deletion (D)) and plasminogen activator inhibitor (PAI-1) (4G/5G insertion/deletion) polymorphisms with MI in the Pakistani population. In MI patients the genotype distribution of the PAI-1 gene was not found to be different when compared with the unaffected controls (P > 0.05, χ² = 1.03). The risk allele 4G was also not associated with MI (P > 0.05, χ² = 0.46, odds ratio (OR) = 1.1 (95% confidence interval (CI) = 0.84–1.43), P > 0.05). Similarly, the genotype frequencies of t-PA I/I, I/D and D/D were not different from the unaffected controls (P > 0.05, χ² = 1.60), and the risk allele “I” was not found to be associated with MI (P > 0.05, χ² = 1.35, OR = 0.86 (95% CI = 0.66–1.11), P > 0.05). However, when the data were distributed along the lines of gender a significant association of the 4G/4G PAI-1 genotype was observed with only the female MI patients (P < 0.05, z-test = 2.21). When the combined genotypes of both the polymorphisms were analyzed, a significant association of MI was observed with the homozygous DD/4G4G genotype (P < 0.01, z-test = 2.61), which was specifically because of the female samples (P = 0.01, z-test = 2.53). In addition smoking (P < 0.001, χ² = 13.52, OR = 3.45 (95% CI = 1.77–6.94)), diabetes (P < 0.001, χ² = 22.45, OR = 8.89 (95% CI = 2.96–29.95)), hypertension (OR = 7.76 (95% CI = 2.88–22.68), P < 0.001) family history (P < 0.001, χ² = 13.72, OR = 3.7 (95% CI = 1.71–8.18)) and lower HDL levels (P < 0.05) were found to be significantly associated with the disease. In conclusion the PAI-1 gene polymorphism was found to have a gender specific role in the female MI patients.     

Association of a LSP1 gene rs3817198T>C polymorphism with breast cancer risk: evidence from 33,920 cases and 35,671 controls

Published data on the association between lymphocyte-specific protein 1 (LSP1) rs3817198T>C polymorphism and breast cancer risk are inconclusive. Hence, we conducted a meta-analysis of the LSP1 gene and risk of breast cancer to obtain the most reliable estimate of the association. PubMed, Embase and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were extracted and pooled to assess the strength of the association between the LSP1 rs3817198T>C polymorphism and risk of breast cancer. A total of seven eligible studies including 33,920 cases and 35,671 controls based on the search criteria were involved in this meta-analysis. The distributions of genotypes in the controls were all in agreement with Hardy–Weinberg equilibrium. We observed that the LSP1 rs3817198T>C polymorphism was significantly correlated with breast cancer risk when all studies were pooled into the meta-analysis (the allele contrast model: OR = 1.06, 95% CI = 1.04–1.08; the homozygote codominant: OR = 1.14, 95% CI = 1.01–1.28). In the stratified analysis by ethnicity, significant association was observed in Caucasians for CC versus TT homozygote codominant model (OR = 1.25; 95% CI = 1.03–1.52) and for the recessive model (OR = 1.22; 95% CI = 1.02–1.47). There was significant association observed in Africans for CC versus TT homozygote codominant model (OR = 0.45; 95% CI = 0.22–0.92) and for the recessive model (OR = 0.43; 95% CI=0.22–0.88). Also, significant association was observed in mixed ethnicities for CC versus TT homozygote codominant model (OR = 1.12; 95% CI = 1.05–1.19). When stratified by study design, statistically significantly elevated risk was found in nested case–control studies (CC vs. TT: OR = 1.12, 95% CI = 1.05–1.19). But no significant association was observed for all comparison models between LSP1 rs3817198T>C polymorphism and breast cancer risk in hospital-based and people-based studies. When stratified by BRCA1 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (the allele contrast model: OR = 1.07, 95% CI = 1.01–1.14; the dominant model: OR = 1.09, 95% CI = 1.00–1.18). And significant association was found in the BRCA2 mutation carriers in the allele contrast (OR = 1.11, 95% CI = 1.03–1.20), the homozygote codominant (OR = 1.23, 95% CI = 1.04–1.47), the heterozygote codominant (OR = 1.12, 95% CI = 1.00–1.25) and the dominant models (OR = 1.14, 95% CI = 1.03–1.27). There was significant association between LSP1 rs3817198T>C polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort in all comparison models (the allele contrast model: OR = 1.08, 95% CI = 1.03–1.13; CC vs. TT: OR = 1.16, 95% CI = 1.05–1.29; TC vs. TT: OR = 1.09, 95% CI = 1.01–1.16; the dominant model: OR = 1.10, 95% CI = 1.03–1.17; the recessive model: OR = 1.12, 95% CI = 1.01–1.23). In conclusion, this meta-analysis suggests that the LSP1 rs3817198T>C polymorphism is a low-penetrant risk factor for developing breast cancer but may not be in Africans.