MspI and Ile462Val Polymorphisms in CYP1A1 and Overall Cancer Risk: A Meta-Analysis

Background

Cytochrome P450 1A1 (CYP1A1) is a member of the CYP1 family, which is a key enzyme in the metabolism of many endogenous substrates and exogenous carcinogens. To date, many studies have examined the association between CYP1A1 MspI and Ile462Val polymorphisms and cancer risk in various populations, but their results have been conflicting rather than consistent.

Methods

To assess this relationship more precisely, a meta-analysis based on 198 publications was performed. Odds ratios (OR) and corresponding 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with a chi-square-based Q-test.

Results

Overall, a significant elevated risk of cancer was associated with CYP1A1 MspI and Ile462Val polymorphisms for all genetic models studied. Further stratified analysis by cancer types revealed that the MspI polymorphism may increase the risk of lung cancer and cervical cancer whereas the Ile462Val polymorphism may contribute to a higher risk of lung cancer, leukemia, esophageal carcinoma, and prostate cancer. In the subgroup analysis by ethnicity, obvious associations were found in the Asian population for the MspI polymorphism while an increased risk of cancer was observed in Asians and Caucasians for the Ile462Val polymorphism.

Conclusions

The results of this meta-analysis suggest that CYP1A1 MspI and Ile462Val polymorphisms contribute to increased cancer susceptibility among Asians. Additional comprehensive system analyses are required to validate this association and other related polymorphisms.     

miR-196a2 C allele is a low-penetrant risk factor for cancer development

Published data on the association between miR-196a2 T/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 21 studies including 10,441 cases and 12,353 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with miR-196a2 C allele when all studies were pooled into the meta-analysis (TC vs. TT: OR=1.23, 95% CI=1.11-1.36; CC vs. TT: OR=1.30, 95% CI=1.14-1.48; dominant model: OR=1.25, 95% CI=1.13-1.38). In the subgroup analysis by ethnicity, significantly increased risks were found in Asains (TC vs. TT: OR=1.24, 95% CI=1.10-1.40; CC vs. TT: OR=1.31, 95% CI=1.13-1.52; dominant model: OR=1.26, 95% CI=1.12-1.41) but with bordline statistical significance in Caucasians (TC vs. TT: OR=1.15, 95% CI=1.00-1.31). In the subgroup analysis by cancer type, statistically significantly increased risks were found for breast cancer (TC vs. TT: OR=1.15, 95% CI=1.01-1.31; CC vs. TT: OR=1.30, 95% CI=1.01-1.68; dominant model: OR=1.22, 95% CI=1.00-1.50; and recessive model: OR=1.11, 95% CI=1.01-1.23) and lung cancer (CC vs. TT: OR=1.30, 95% CI=1.10-1.54; and recessive model: OR=1.18, 95% CI=1.02-1.36). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TC vs. TT: OR=1.30, 95% CI=1.13-1.49; CC vs. TT: OR=1.37, 95% CI=1.14-1.66; dominant model: OR=1.32, 95% CI=1.15-1.53) and population-based studies (CC vs. TT: OR=1.19, 95% CI=1.06-1.35; dominant model: OR=1.13, 95% CI=1.01-1.25). Despite some limitations, this meta-analysis suggests that the miR-196a2 C allele is a low-penetrant risk factor for cancer development.     

Interactions between <Emphasis Type="Italic">CYP1A1</Emphasis> polymorphisms and cigarette smoking are associated with the risk of hepatocellular carcinoma: evidence from epidemiological studies

The Cytochrome P-450 1A1 (CYP1A1) gene has been implicated in the etiology of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in CYP1A1 gene with HCC risk. Published literature from PubMed, Embase, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Eight studies (1,752 cases and 2,279 controls) for Ile-Val polymorphism and eight studies (933 cases and 1,449 controls) for MspI polymorphism were identified. The results showed that there was no statistically significant association between the Ile-Val polymorphism and HCC risk under all genetic models (co-dominant model: Val/Val vs. Ile/Ile: OR = 1.62, 95% CI 0.96-2.72 and Ile/Val vs. Ile/Ile: OR = 1.15, 95% CI 0.87-1.52; dominant model: OR = 1.25, 95% CI 0.92-1.70; recessive model: OR = 1.48, 95% CI 0.99-2.21). The MspI polymorphism was also not associated with HCC risk (co-dominant model: m2m2 vs. m1m1: OR = 1.09, 95% CI 0.83-1.42 and m1m2 vs. m1m1: OR = 1.30, 95% CI 1.05-1.61; dominant model: OR = 1.20, 95% CI 0.99–1.45; recessive model: OR = 0.94, 95% CI 0.74-1.18). However, the significant associations were found between both the Ile–Val and MspI polymorphisms and HCC risk among the cigarette smoking subjects (Ile-Val: OR = 1.40, 95% CI 1.06-1.85; MspI: OR = 2.65, 95% CI 1.47-4.77). The present meta-analysis indicated that the MspI and Ile-Val polymorphisms of CYP1A1 may play important roles in increasing susceptibility to smoking-related HCC.     

CYP1A1 MspI polymorphism is associated with prostate cancer susceptibility: evidence from a meta-analysis

Cytochrome P450 1A1 (CYP1A1), an important phase I xenobiotic metabolizing enzyme, is responsible for metabolizing numerous carcinogens, particularly polycyclic aromatic hydrocarbons. The genetic polymorphism of CYP1A1 at the site of MspI (CYP1A1 MspI) has been implicated in prostate cancer risk, but the results of individual studies remain conflicting and inconclusive. The aim of this meta-analysis was to investigate the association of CYP1A1 MspI polymorphism with prostate cancer risk more precisely. We performed a comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases from their inception up to September 20, 2012 for relevant publications. The pooled odds ratios with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the association of CYP1A1 MspI polymorphism with prostate cancer risk. In addition, stratified analyses by ethnicity and sensitivity analyses were conducted for further estimation. Sixteen eligible publications with 6,411 subjects were finally included into the meta-analysis after checking the retrieved papers. Overall, meta-analysis of total studies suggested that individuals carrying the TC genotype and a combined C genotype (CC + TC) were more susceptible to prostate cancer (OR_{TC vs. TT} = 1.33, 95 % CI 1.10–1.61, P _OR = 0.004; OR_{CC+TC vs. TT} = 1.27, 95 % CI 1.05–1.55, P _OR = 0.016). Stratified analysis of high quality studies also confirmed the significant association (OR_{TC vs. TT} = 1.32, 95 % CI 1.04–1.67, P _OR = 0.024; OR_{CC+TC vs. TT} = 1.30, 95 % CI 1.02–1.66, P _OR = 0.035). In subgroup analyses by ethnicity, a significant association between the CYP1A1 MspI polymorphism and risk of prostate cancer was found among Asians (OR_{TC vs. TT} = 1.44, 95 % CI 1.20–1.72, P _OR < 0.001; OR_{CC+TC vs. TT} = 1.33, 95 % CI 1.12–1.58, P _OR = 0.001), but not in Caucasians or mixed populations. The meta-analysis suggests an important role of the CYP1A1 MspI polymorphism in the risk of developing prostate cancer, especially in Asians.     

Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and ovarian cancer risk: a meta-analysis

This meta-analysis aims to examine whether the genotype status of MspI, Ile462Val, and Thr461Asn polymorphisms in Cytochrome P450 1A1 (CYP1A1) is associated with ovarian cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed effects or random effects models. Concerning MspI polymorphism, seven studies were eligible (1,051 cases and 1,613 controls); 11 studies were eligible (1,680 cases and 3,345 controls) for Ile462Val and three studies were eligible (349 cases and 785 controls) for Thr461Asn. Ile462Val polymorphism seemed to confer elevated ovarian cancer risk concerning homozygous carriers (pooled OR?=?2.65, 95?% CI: 1.40-5.03, p?=?0.003, fixed effects), as well as at the recessive model (pooled OR?=?2.10, 95?% CI: 1.13-3.92, p?=?0.020, fixed effects); these findings were replicated upon Caucasian subjects. MspI polymorphism was not associated with ovarian cancer risk (for heterozygous TC vs TT carriers pooled OR?=?1.10, 95?% CI: 0.91-1.34, p?=?0.329, fixed effects; for homozygous CC vs. TT carriers pooled OR?=?1.11, 95?% CI: 0.65-1.90, p?=?0.693, fixed effects). With respect to Thr461Asn polymorphism a finding of borderline statistical significance emerged, pointing to marginally elevated ovarian cancer risk in heterozygous Thr/Asn carriers (pooled OR?=?1.62, 95?% CI: 0.97-2.70, p?=?0.066, fixed effects), but not in homozygous Asn/Asn carriers (pooled OR?=?1.40, 95?% CI: 0.18-10.89, p?=?0.749, fixed effects). Ile462Val status seems to represent a meaningful risk factor for ovarian cancer in Caucasians. Additional case-control studies of high methodological quality are needed in order to further substantiate and enrich the present findings. Special attention should be paid upon the design of future studies; Asian and African populations should represent points of focus.     

CYP1A1 Ile462Val Polymorphism Contributes to Lung Cancer Susceptibility among Lung Squamous Carcinoma and Smokers: A Meta-Analysis

Many studies have examined the association between the CYP1A1 Ile462Val gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. Ultimately, 43 case-control studies, comprising 19,228 subjects were included. A significantly elevated lung cancer risk was associated with 2 Ile462Val genotype variants (for Val/Val vs Ile/Ile: OR = 1.22, 95% CI = 1.08–1.40; for (Ile/Val +Val/Val) vs Ile/Ile: OR = 1.15, 95% CI = 1.07–1.23) in overall population. In the stratified analysis, a significant association was found in Asians, Caucasians and lung SCC, not lung AC and lung SCLC. Additionally, a significant association was found in smoker population and not found in non-smoker populations. This meta-analysis suggests that the Ile462Val polymorphisms of CYP1A1 correlate with increased lung cancer susceptibility in Asian and Caucasian populations and there is an interaction with smoking status, but these associations vary in different histological types of lung caner.     

Lack of association between miR-149 C>T polymorphism and cancer susceptibility: a meta-analysis based on 4,677 cases and 4,830 controls

To derive a more precise estimation of the relationship between miR-149 C>T polymorphism and cancer risk, a meta-analysis was performed. A total of 8 studies including 4,677 cases and 4,830 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-149 T allele when all studies were pooled into the meta-analysis (CT vs. CC: OR = 0.977, 95 % CI = 0.882-1.082; TT vs. CC: OR = 0.985, 95 % CI = 0.857-1.132; dominant model: OR = 0.984, 95 % CI = 0.893-1.084; recessive model: OR = 1.026, 95 % CI = 0.931-1.132). In the subgroup analysis by ethnicity or study design, no significantly increased risks were found under all models. When stratified by cancer type, there were no significant cancer risk changes for lung cancer, breast cancer or colorectal cancer when miR-149 T allele was included. In conclusion, this meta-analysis suggests that the miR-149 C>T polymorphism may not contribute to cancer susceptibility.     

APE1 Asp148Glu gene polymorphism and lung cancer risk: a meta-analysis

Many studies have examined the association between the APE1 T1349G (Asp148Glu) gene polymorphisms and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed, Embase, Web of Science, and CNKI database was searched for case–control studies published up to June 2010. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, ten studies, comprising 2,696 lung cancer cases and 3,948 controls were included. Overall, for the G allele carriers (TG + GG) versus homozygote TT, the pooled OR was 1.037 (95% CI = 0.928–1.159 P = 0.001 for heterogeneity), for GG versus TT the pooled OR was 0.997 (95% CI = 0.861–1.154 P = 0.005 for heterogeneity). In the stratified analysis by ethnicity, significantly risks were not found among Asians or Caucasians. However, in the subgroup analyses by smoking status, significantly risks were found among smokers not in non-smokers. This meta-analysis suggested that the APE1 T1349G (Asp148Glu) polymorphism was not associated with lung cancer risk among Asians or Caucasians. But, the APE1 G allele was an increased risk factor for developing lung cancer among smokers.     

Association between the G-protein β3 subunit C825T polymorphism with essential hypertension: a meta-analysis in Han Chinese population

We aimed to evaluate the contribution of the G-protein β3 subunit C825T (GNB3-C825T) polymorphism to essential hypertension (EH) in Han Chinese population by performing meta-analysis. A meta-analysis was performed in 12 case-control genetic association studies including 3,020 hypertension patients and 2,790 controls from MEDLINE (PubMed) and the China National Knowledge Infrastructure platforms. The STATA 10.0 software was used in analysis. Overall, there was no significant association between the GNB3-C825T polymorphism and EH in neither additive [TT vs. CC: OR (95 % CI) = 1.11 (0.74-1.69), P = 0.61; TC vs. CC: OR (95 % CI) = 1.08 (0.89-1.31), P = 0.42], nor dominant [TT + TC vs. CC: OR (95 % CI) = 1.11 (0.86-1.42), P = 0.43] and nor recessive [TT vs. TC + CC: OR (95 % CI) = 1.04 (0.75-1.44), P = 0.81] genetic models. Although further subgroup analysis found statistically significant results [T vs. C: OR (95 % CI) = 1.50 (1.05-2.15), P = 0.03] in the southern population, but after exclusion one particular study, the significant association was disappeared. No significant result was found in the northern Han Chinese population. There was no significant association identified between GNB3-C825T polymorphism and EH in Han Chinese population. Further larger sample and well-designed studies are needed to assess the genetic association particularly in the southern Han Chinese population.     

Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and cervical cancer risk: a meta-analysis

This meta-analysis aims to examine whether the genotype status of MspI and Ile462Val polymorphisms in Cytochrome-P450 1A1 (CYP1A1) is associated with cervical cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random effects models. Concerning MspI polymorphism, six studies were eligible (722 cases and 770 controls); four studies were eligible (350 cases and 519 controls) for Ile462Val. MspI polymorphism was associated with elevated cervical cancer risk (for heterozygous TC vs. TT carriers OR = 1.50, 95% CI: 0.93–2.42, random effects; for homozygous CC vs. TT carriers OR = 2.66, 95% CI: 1.14–6.19, random effects). Similarly, Ile462Val polymorphism was associated with elevated cervical cancer risk (for heterozygous Ile/Val vs. Ile/Ile carriers OR = 2.36, 95% CI: 1.10–5.08, random effects; for homozygous Val/Val vs. Ile/Ile carriers OR = 2.73, 95% CI: 1.21–6.15, fixed effects). The results were replicated upon Caucasian subjects, who represented the majority of existing data. The two examined CYP1A1 genotype polymorphisms seem to confer additional risk for cervical cancer. Accumulation of further data seems mandatory for future race-specific analyses and for the demonstration of CYP1A1-smoking interactions.     

Current evidence on the relationship between CYP1B1 polymorphisms and lung cancer risk: a meta-analysis

The association between single-nucleotide polymorphisms (SNPs) of the CYP1B1 gene and lung cancer risk is still ambiguous. In this meta analysis, we assessed 10 case–control studies included 7,067 cases and 9,374 controls of the association between CYP1B1 SNPs of Leu432Val (rs1056836, 432C>G), Asn453Ser (rs1800440, 453A>G), Ala119Ser (rs1056827, 119G>T), Arg48Gly (rs10012, 48C>G) and the risk of lung cancer. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of association between the polymorphism and lung cancer risk under codominant model, dominant model and additive model respectively. Although there were limitations, this meta analysis indicated that individuals with 432GG genotype had a 39.7% higher risk of having lung cancer than those with the 432CC genotype, and individuals with the 432G allele had a 26.3% increased risk as well. An increased risk of lung cancer of 2.13 fold was observed in individuals with 119TT genotype. For Arg48Gly, individuals with 48GG genotype had a significantly increased risk of lung cancer compared with individuals with 48CC (OR 3.859; 95% CI 2.536–5.87). Elevated risk of lung cancer were observed in dominant model (OR 2.115; 95% CI 1.653–2.705) as well. The risk of lung cancer was elevated as the frequency of G allele increased in additive model (P = 0.000). For individuals with the polymorphism at codon 453, no evidence of such association was observed. Furthermore, a possible association between the CYP1B1 polymorphism at codon 432 and the lung cancer could be detected in individuals of Caucasian origin, while a negative association was suggested in Asians and African-Americans. An increased lung cancer risk was also found in women with polymorphism at codon 453. These results are supportive for the hypothesis that the CYP1B1 432GG, 119TT and 48GG genotypes are low-penetrance risk factors for developing lung cancer, and further studies are needed to validate these associations.     

MTHFR C677T polymorphism contributes to colorectal cancer susceptibility: evidence from 61 case–control studies

Methylenetetrahydrofolate reductase (MTHFR) is believed to be involved in folate metabolism which plays a critical role in carcinogenesis. To date, many case-control studies have investigated the association between MTHFR C677T polymorphism and colorectal cancer risk. However, the results were inconsistent. In order to derive a more precise estimation of the association, we conducted this meta-analysis. This meta-analysis recruited 61 published studies which were selected by a search of PubMed up to 31st September 2011, including 16,111 colorectal cancer cases and 23,192 controls. We used crude odds ratios (ORs) with 95?% confidence intervals (CIs) to assess the association between MTHFR C677T polymorphism and colorectal cancer susceptibility. Our results showed that MTHFR C667T polymorphism contributed to the decreased colorectal cancer risk in overall population (for TT vs. CC: OR?=?0.89, 95?% CI?=?0.82-0.97; for TT vs. CT/CC: OR?=?0.88, 95?% CI?=?0.83-0.92). In subgroup analysis by ethnicity, the results also indicated a correlation between the T allele of MTHFR C667T and the colorectal cancer risk in Asian population (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.69-0.97; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.74-0.90). Additionally, the correlation was also observed in male subgroup in sub-analysis by gender (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.71-0.93; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.71-0.92). In summary, our meta-analysis strongly indicated the MTHFR C667T polymorphism was associated with a reduced risk of CRC.     

CYP1A1 genetic polymorphisms,tobacco smoking and lung cancer risk in a French Caucasian population

The CYP1A1 gene encoding for an enzyme involved in the metabolic activation of important tobacco carcinogens could be implicated in smoking-induced lung cancer. Given the strong association between tobacco smoking and lung cancer, the effect of tobacco smoke exposure has to be taken into account when studying the potential association between lung cancer and CYP1A1 genotypes. The effect of two CYP1A1 genetic polymorphisms (Mspl and IIe-Val) on lung cancer risk were evaluated using peripheral blood DNA from 150 lung cancer patients and 171 controls. The Mspl sitepresent allele was found among 19.3% of both cases and controls and the variant allele Val among 6.7% of cases and 8.8% of controls. Lung cancer risks associated with the Mspl site-present allele (OR= 0.9; 95%Cl: 0.5-1.8) or with the Val allele (OR= 0.8; 95%Cl: 0.3-1.9) were not increased after adjustment for tobacco and asbestos exposures. These results persisted when analyses were stratified on smoking status, daily consumption of tobacco or duration of smoking. Similar findings were obtained when squamous cell or small cell carcinomas were studied separately. This study thus suggests a minor role for the known CYP1A1 gene polymorphisms in predisposition to lung cancer among Caucasian populations.     

CYP1A1 Ile462Val is a risk factor for ovarian cancer development

Published data on the association between CYP1A1 gene polymorphism and ovarian cancer risk are conflicting and heterogeneous. To derive a more precise estimation of the relationship, a meta-analysis was performed. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed for heterozygous, homozygous, dominant model, recessive model and allele, respectively. A total of 15 case-control studies were identified, among which, 13 studies (1815 cases and 3501 controls) were eligible for CYP1A1 Ile(462)Val and nine studies (2495 cases and 3553 controls) were eligible for CYP1A1 Msp1. Overall, Ile(462)Val was significantly associated with ovarian cancer, with homozygous carriers (Val/Val vs. Ile/Ile: OR=2.64; 95% CI: 1.63-4.28) and recessive model (Val/Val vs. Ile/Ile and Ile/Val: OR=2.30; 95% CI: 1.45-3.65) being risk factors for ovarian cancer development. In the subgroup analysis by ethnicity, significantly increased risks were found for Caucasians (homozygous carriers: OR=4.91; 95% CI: 2.07-11.66; recessive model: OR=3.26; 95% CI: 1.41-7.50) and Asians (homozygous carriers: OR=3.06; 95% CI: 1.48-6.33; recessive model: OR=2.75; 95% CI: 1.40-5.41; Val allele: OR=1.67; 95% CI: 1.19-2.35). However, no significant associations were found between Msp1 and ovarian cancer in the overall analyses or the subgroup analyses by ethnicity. This meta-analysis denotes the importance for in-depth research regarding of gene-gene, gene-environment interactions, race-specific and histological subtypes specific to obtain a more conclusive response about the function of CYP1A1 in ovarian cancer.     

Prostate cancer with variants in CYP17 and UGT2B17 genes: a meta-analysis

Both CYP17 and UGT2B17 are suggested to be potential risk factors of prostate cancer (PCa). To date, many studies have evaluated the relationship between CYP17 T-34C and UGT2B17 Del polymorphisms and Prostate cancer with conflicting results. Here, we performed comprehensive meta-analyses of over 25 studies, including results from about 17,000 subjects on the association of CYP17 T-34C and UGT2B17 Del polymorphisms with Prostate cancer. Overall, no significant associations between CYP17 T-34C polymorphism and Prostate cancer risk were found for T versus C (P=0.63), TT versus CC (P=0.52), TT+TC versus CC (P=0.40) or TT versus TC+CC (P=0.98), though there was a marginally significant association with the UGT2B17 Del polymorphism under Del/Del versus Ins/Ins +Ins/Del (P=0.05). In an analysis of various subgroups, there were no substantially significant associations with the CYP17 T-34C polymorphism; while there was a significant association for the UGT2B17 Del/Del genotype in a subgroup of men-based controls (P < 0.0001). The current meta-analysis results suggest that the CYP17 T-34C polymorphism may not be associated with Prostate cancer, while the UGT2B17 Del polymorphism may significantly contribute to prostate cancer susceptibility in men. These findings also support the idea that CYP17 has no significant effects on androgen levels, while UGT2B17 does.     

GSTP1 Ile105Val polymorphism is associated with lung cancer risk among Asian population and smokers: An updated meta-analysis

Many studies have examined the association between the GSTP1 Ile105Val (rs 1695) gene polymorphism and lung cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The PubMed and CNKI database was searched for case–control studies published up to July 2012. Data were extracted and pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated. Ultimately, 42 studies, comprising 12,304 lung cancer cases and 15,729 controls were included. Overall, for G allele carriers (GA + GG) versus homozygote AA, the pooled OR was 1.05 (95 % CI 0.99–1.10 P = 0.092 for heterogeneity), for GG versus AA the pooled OR was 1.04 (95 % CI 0.96–1.12 P = 0.084 for heterogeneity). In the stratified analysis by ethnicity, gender, histological types of lung cancer and smoking status, a significant association was found in Asians and smokers, not in Caucasian or mixed population, Male, Female population, lung AC, SCC, SCLC or non-smokers. Publication bias was found by using the funnel plot and Egger’s test. Overall, there is no evidence showing a significant correlation between GSTP1 Ile105Val gene polymorphism and lung cancer risk in overall population, however stratified analysis by ethnicity, histology, gender and smoking status, it correlate with increased lung cancer susceptibility among Asians and smokers.     

The ?159C/T polymorphism in the CD14 gene and the risk of asthma: a meta-analysis

The -159C/T polymorphism in the CD14 gene has been implicated in susceptibility to asthma, but a large number of studies have reported inconclusive results. The aim of this study is to investigate the association between the -159C/T polymorphism in the CD14 gene and the risk of asthma by meta-analysis. We searched Pubmed, Embase, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on April 20, 2010). Statistical analysis was performed by using the softwares Revman 4.2 and STATA 10.0. A total of 17 case-control studies in 17 articles (4,246 cases and 3,631 controls) were included in this meta-analysis. There was no association between this polymorphism and asthma risk in combined analyses (odds ratio (OR)?=?0.86 and 95% confidence interval (95% CI)?=?0.72-1.02, P?=?0.09 for TC?+?TT vs. CC). In the subgroup analysis by age, ethnicity, and atopic status, no significant associations of asthma risks were obtained from age groups, ethnic groups, and atopic groups for TC?+?TT vs. CC comparison. For atopic population, significant decreased atopic asthma risks were found among Asian population (OR?=?0.69, 95% CI 0.52-0.92, P?=?0.01) and children population (OR?=?0.69, 95% CI 0.54-0.89, P?=?0.0004) for TC?+?TT vs. CC comparison. This meta-analysis suggests that CD14 is a candidate gene for atopic asthma susceptibility. The -159C/T polymorphism may be a protective factor for atopic asthma in Asian and children. More studies are needed to validate these associations.     

The association between common genetic variant of microRNA-146a and cancer susceptibility

Published data on the association between microRNA-146a (miR-146a) G/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 23 studies including 10,585 cases and 12,183 controls were used in the meta-analysis. Overall, no significant associations were found between miR-146a G/C polymorphism and cancer risk when all studies pooled into the meta-analysis (GC vs. CC: OR=1.08, 95% CI=0.94-1.24; GG vs. CC: OR=1.13, 95% CI=0.93-1.37; dominant model: OR=1.09, 95% CI=0.94-1.26). In the subgroup analysis by ethnicity, still no significant associations were found. In the subgroup analysis by cancer type, statistically significantly increased risks were found for papillary thyroid carcinoma (GC vs. CC: OR=3.44, 95% CI=1.86-6.34; GG vs. CC: OR=2.20, 95% CI=1.22-3.99; dominant model: OR=2.68, 95% CI=1.48-4.83). In the subgroup analysis by population-based controls or hospital-based controls, no statistically significantly increased risks were found. Despite some limitations, this meta-analysis suggests that the miR-146a G allele is a low-penetrant risk factor for papillary thyroid carcinoma development.     

CYP1A1 and CYP2D6 polymorphism and risk of lung cancer in a North Indian population.

This case-control study was conducted to examine the association between the CYP1A1 and CYP2D6 genotypes and lung cancer risk among North Indians. The estimated relative risk for lung cancer associated with the CYP1A1 Val/Val allele was 2.68, and was four-fold when cases with small cell lung cancer (SCLC) were considered alone. With regard to the metabolism of debrisoquine, no poor metabolizers were found amongst the subjects. The odds ratio of risk with the heterozygous extensive metabolizer (HEM) genotype was 1.5. However, in the presence of at least a single copy of the variant CYP1A1 MspI allele and the CYP2D6 HEM genotype, the risk was two-fold for squamous cell carcinoma (SQCC). When the CYP1A1 Val/Val and CYP2D6 HEM genotypes were taken together, the risk for SCLC was four-fold. Stratified analysis indicated an interaction between bidi smoking and variant CYP1A1 genotypes on the risk for SQCC and SCLC. Heavy smokers (Brinkman index>400) with Val/Val genotypes were at a very high risk of developing lung cancer (odds ratio 29.30, 95% confidence interval 2.42-355, p=0.008). Heavy smokers with CYP1A1 MspI (CYP1A1*1/2A or CYP1A1*2A/*2A) genotype had a seven-fold risk for SCLC compared with non-smokers. This study is the first to be carried out on a North Indian population, and, although small, suggests that CYP1A1 and CYP2D6 polymorphisms might have a role in determining the risk for lung cancer and should be investigated further.