Xiao-Feng He

Association between the XRCC3 T241M polymorphism and risk of cancer: evidence from 157 case-control studies.

The T241M polymorphism in the X-ray cross-complementing group 3 (XRCC3) had been implicated in cancer susceptibility. The previous published data on the association between XRCC3 T241M polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC3 T241M (61,861 cases and 84,584 controls from 157 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR]=1.07, 95% confidence interval [CI]=1.00-1.13; recessive model: OR=1.15, 95% CI=1.08-1.23; additive model: OR=1.17, 95% CI=1.08-1.28) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of bladder cancer and breast cancer, especially in Caucasians. In addition, significantly decreased lung cancer risk was also observed. In summary, this meta-analysis suggests the participation of XRCC3 T241M in the susceptibility for bladder cancer and breast cancer, especially in Caucasians, and XRCC3 T241M polymorphism is associated with decreased lung cancer risk. Moreover, our work also points out the importance of new studies for T241M association in some cancer types, such as gastric cancer, colorectal cancer, and melanoma skin cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC3 polymorphism in cancer development.

Association between the CYP1A1 T3801C polymorphism and risk of cancer: evidence from 268 case-control studies.

T3801C is a common polymorphism in CYP1A1, showing differences in its biological functions. Case-control studies have been performed to elucidate the role of T3801C in cancer, although the results are conflicting and heterogeneous. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and T3801C (55,963 cases and 76,631 controls from 268 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ratio [OR]=1.14, 95% confidence interval [CI]=1.09-1.19; recessive model: OR=1.23, 95% CI=1.12-1.34; CC vs. TT: OR=1.31, 95% CI=1.19-1.45; TC vs. TT: OR=1.12, 95% CI=1.07-1.18; additive model: OR=1.14, 95% CI=1.09-1.19) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of cervical cancer, head and neck cancer, hepetocellular cancer, leukemia, lung cancer, prostate cancer and breast cancer. In addition, significantly decreased colorectal cancer risk was also observed. In summary, this meta-analysis suggests the participation of CYP1A1 T3801C is a genetic susceptibility for some cancer types. Moreover, our work also points out the importance of new studies for T3801C association in some cancer types, such as gallbladder cancer, Asians of acute myeloid leukemia, and thyroid cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the CYP1A1 T3801C polymorphism in cancer development.

Genetic variation of XPA gene and risk of cancer: A systematic review and pooled analysis

XPA, a zinc‐finger DNA‐binding protein, play an important role in both global genome and transcription‐coupled repair pathways. XPA −4G>A polymorphism was identified in the 5′ noncoding region, located four nucleotides upstream of the ATG start codon. Previous studies have shown that this polymorphism may affect mRNA tertiary structure and stability and play a role in susceptibility to cancer. However, the results remained controversial. To derive a more precise estimation of association between this polymorphism and risk of different types of cancer, we performed a meta‐analysis based on 36 case–control or case–cohort studies, including a total of 11,700 cases and 15,033 controls. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, no significantly elevated cancer risk was found in all genetic models when eligible studies were pooled into the meta‐analysis. In the stratified analyses, we found that individuals with A‐allele had a higher risk of lung cancer (AA versus GG: OR = 1.25, 95% CI = 1.09–1.43; recessive model: OR = 1.31, 95% CI = 1.16–1.48). When stratified by ethnicity, significantly elevated risks were observed among Asian populations (AA versus GG: OR = 1.31, 95% CI = 1.01–1.70; dominant model: OR = 1.14, 95% CI = 1.00–1.30). This meta‐analysis suggests that XPA −4G>A polymorphism is associated with increased lung cancer risk and may be a low‐penetrant risk factor in Asian ethnicity for cancer development.

Lack of association between BARD1 Cys557Ser variant and breast cancer risk: a meta-analysis of 11,870 cases and 7,687 controls.

PurposeThe BRCA1-associated RING domain (BARD1) gene has been identified as a high-penetrance gene for breast cancer, whose germline and somatic mutations were reported in both non-BRCA1/2 hereditary site-specific and sporadic breast cancer cases. Some association studies suggested that the BRAD1 Cys557Ser variant might be associated with increased risk of breast cancer, but the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, this meta-analysis was performed.MethodsEligible studies were identified by searching several databases for relevant reports published before March 2011. In total, 14 studies (11,870 cases and 7,687 controls) were included in the present meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) for breast cancer risk associated with Cys557Ser carrier was estimated.ResultsThe carrier frequency of the Cys557Ser mutation was 3.85% (457/11,870) in patients with breast cancer and 3.29% (253/7,687) in healthy controls. When all studies were pooled into the meta-analysis, there was no evidence for significant association between Cys557Ser mutation and breast cancer risk (OR 1.14, 95% CI 0.94–1.34). In the subgroup analyses by design of experiment and family history with BRCA1/2 status (unselected cases, family history with non-BRCA1/2 cases, and family history with BRCA1/2-positive cases), no significant associations were found in any subgroup of population.ConclusionsThis meta-analysis strongly suggests that BARD1 Cys557Ser mutation is not associated with increased breast cancer risk.

Lack of association of ADH1C genotype with breast cancer susceptibility in Caucasian population: A pooled analysis of case–control studies

PURPOSE Recent epidemiological studies demonstrated that alcohol dehydrogenase 1C (ADH1C) alleles that result in acetaldehyde accumulation in the cells can enhance a drinkers risk of developing alcohol related cancer in a variety of tissues. The published data on the association between ADH1C alleles and breast cancer occurrence in Caucasians have led to in contradictory results. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship. METHODS A total of 12 studies were identified to the meta-analysis, including 6159 cases and 5732 controls from Caucasians. The pooled odds ratio (OR) with 95% confidence interval (CI) for breast cancer risk associated with ADH1C genotype was estimated. RESULTS Overall, no significantly elevated breast cancer risk was found in all genetic models when all studies were pooled into the meta-analysis (ADH1C(1-2) vs. ADH1C(2-2): OR 1.07, 95% CI 0.97-1.19; ADH1C(1-1) vs. ADH1C(2-2): OR 1.16, 95% CI 0.94-1.43; dominant model: OR 1.07, 95% CI 0.97-1.18; recessive model: OR 1.06, 95% CI 0.93-1.20). There was no evidence for the association between ADH1C genotype and breast cancer risk in subgroup analyses based on design of experiment and menopausal status. And for the additive model, individuals carrying the ADH1C*(1) allele were not significantly associated with increased risk to breast cancer (OR 1.01, 95% CI 0.97-1.06). CONCLUSION This meta-analysis suggests that ADH1C polymorphism may not be associated with breast cancer development in Caucasians. And larger scale primary studies are required to further evaluate the interaction of ADH1C polymorphism and breast cancer risk in specific populations.

Association between the XPG Asp1104His and XPF Arg415Gln polymorphisms and risk of cancer: a meta-analysis.

Backgroud The XPG (xeroderma pigmentosum type G) Asp1104His and XPF (xeroderma pigmentosum type F) Arg415Gln polymorphisms had been implicated in cancer susceptibility. The previous published data on the association between XPG Asp1104His and XPF Arg415Gln polymorphisms and cancer risk remained controversial. Methodology/Principal Findings To derive a more precise estimation of the association between the XPG Asp1104His and XPF Arg415Gln polymorphisms and overall cancer risk, we performed a meta-analysis to investigate the association between cancer susceptibility and XPG Asp1104His (32,162 cases and 39,858 controls from 66 studies) and XPF Arg415Gln polymorphisms (17,864 cases and 20,578 controls from 32 studies) in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly elevated cancer risk was found when all studies were pooled into the meta-analysis of XPG Asp1104His (dominant model: OR = 1.05, 95% CI = 1.00–1.10; Asp/His vs. Asp/Asp: OR = 1.06, 95% CI = 1.01–1.11). In the further stratified and sensitivity analyses, significantly decreased lung cancer risk was found for XPF Arg415Gln (dominant model: OR = 0.82, 95% CI = 0.71–0.96; Arg/Gln versus Arg/Arg: OR = 0.83, 95% CI = 0.71–0.97; additive model: OR = 0.83, 95% CI = 0.72–0.95) and significantly increased other cancer risk was found among hospital-based studies for XPG Asp1104His (dominant model: OR = 1.23, 95% CI = 1.02–1.49). Conclusions/Significance In summary, this meta-analysis suggests that XPF Arg415Gln polymorphism may be associated with decreased lung cancer risk and XPG Asp1104His may be a low-penetrant risk factor in some cancers development. And larger scale primary studies are required to further evaluate the interaction of XPG Asp1104His and XPF Arg415Gln polymorphisms and cancer risk in specific populations.

Association between CYP1A2 and CYP1B1 polymorphisms and colorectal cancer risk: a meta-analysis.

Background The previous published data on the association between CYP1A2*F (rs762551), CYP1B1 Leu432Val (rs1056836), Asn453Ser (rs180040), and Arg48Gly (rs10012) polymorphisms and colorectal cancer risk remained controversial. Methodology/Principal Findings The purpose of this study is to evaluate the role of CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly genotypes in colorectal cancer susceptibility. We performed a meta-analysis on all the eligible studies that provided 5,817 cases and 6,544 controls for CYP1A2*F (from 13 studies), 9219 cases and 10406 controls for CYP1B1 Leu432Val (from 12 studies), 6840 cases and 7761 controls for CYP1B1 Asn453Ser (from 8 studies), and 4302 cases and 4791 controls for CYP1B1Arg48Gly (from 6 studies). Overall, no significant association was found between CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly and colorectal cancer risk when all the eligible studies were pooled into the meta-analysis. And in the subgroup by ethnicity and source of controls, no evidence of significant association was observed in any subgroup analysis. Conclusions/Significance In summary, this meta-analysis indicates that CYP1A2*F, CYP1B1 Leu432Val, Asn453Ser, and Arg48Gly polymorphisms do not support an association with colorectal cancer, and further studies are needed to investigate the association. In addition, our work also points out the importance of new studies for CYP1A2*F polymorphism in Asians, because high heterogeneity was found (dominant model: I 2 = 81.3%; heterozygote model: I 2 = 79.0).

Lack of association between hOGG1 Ser326Cys polymorphism and breast cancer susceptibility in European population

Recently, we read with great interest the article ‘‘The hOGG1 Ser326Cys polymorphism and breast cancer risk: a meta-analysis’’ published online in August 2010 issue of ‘‘Breast Cancer Research and Treatment’’ [1]. The study of Yuan et al. performed a meta-analysis to make an estimation of the association between the DNA repair gene hOGG1 Ser326Cys polymorphism (rs1052133) and breast cancer susceptibility, and the results showed that individuals who carrying the hOGG1 326Cys allele did not have significantly increased risk of breast cancer compared with those carrying the 326Ser allele. However, in the stratified analysis by ethnicity, the meta-analysis showed the association between hOGG1 326Cys allele in the additive model, and breast cancer was significant in European subject (OR = 0.71, 95% CI = 0.51–0.98), and dominant genetic model (OR = 0.44, 95%CI = 0.25–0.77), and the 326Cys allele plays a protective effect on the carcinogenesis of breast cancer among them. Nevertheless, there are some comments we would like to raise. Using the same search strategy and end-of-search date as those of Yuan et al. [1], we have found that the data reported by Yuan et al. [1] for the study by Zhang et al. [2] do not seem in line with the data provided by Zhang et al. [2] in their original publication. The ethnicity of eligible sample (1,571 cases and 1,244 controls) reported by Yuan et al. [1] are the American population. And three other studies were involved in the European populations [3–5]. Interestingly enough, after carefully studying the data presented by Zhang et al. [2], we found that this study population was restricted to Caucasian women to limit heterogeneity, mostly of central European ancestry. And the data reported by Yuan et al. [1] for the study by Vogel et al. [5] is not included in the stratified analysis for the European population. Hence, the ongoing uncertainly still existed, and the conclusion by Yuan et al. [1] was not entirely credible. In light of the above, we have combined all of the studies for European population into a new meta-analysis, including four case–control studies as described by Yuan et al. [2–5]. Our pooled results indicate that the hOGG1 326Cys allele is not associated with breast cancer risk in European population (Ser/Cys vs. Ser/Ser: OR = 0.76, 95% CI = 0.54–1.07; Cys/Cys vs. Ser/Ser: OR = 0.85, 95% CI = 0.65–1.12; dominant model: OR = 0.78, 95% CI = 0.58–1.07; recessive model: OR = 0.96, 95% CI = 0.74–1.24). And for the additive model (326Cys allele vs. 326Ser allele), individuals carrying the 326Cys allele were not significantly associated with increased risk to breast cancer (OR = 0.93, 95% CI = 0.84–1.04). The meta-analysis was based on currently available evidence and was meant to accurately assess the relationship. We have also read with great interest the recent metaanalysis by Gu et al. [6], the study of Gu et al. [6] had eleven case–control studies, and the results suggest that no significant associations between the hOGG1 Ser326Cys Da-Peng Ding and Ying Zhang contributed equally to this study and should be considered as co-first authors.

Need for clarification of data in the recent meta-analysis about RAD51 135G>C polymorphism and breast cancer risk

Recently, we read with great interest the article ‘‘The TGFBR1*6A/9A polymorphism is not associated with differential risk of breast cancer’’ published online in April 2010 issue of ‘‘Breast Cancer Research and Treatment’’ [1]. The study of Colleran et al. performed a meta-analysis to make an estimation of the association between transforming growth factor beta receptor type I (TGFBR1) 6A/9A polymorphism and breast cancer susceptibility, and the results showed that individuals who carrying the TGFBR1*6A allele did not have significantly increased risk of breast cancer compared with those carrying the TGFBR1*9A allele. Nevertheless, there are some comments we would like to raise. First, the data reported by Colleran et al. [1] for the study by Chen et al. [2] do not seem in line with the data provided by Chen et al. [2] in their original publication. Chen et al. analyzed 223 cases with a diagnosis of breast cancer in histologic subgroup, including ductal carcinoma in situ (DCIS), infiltrating ductal carcinoma (IDC)/infiltrating lobular carcinoma (ILC), and metastatic breast cancer. However, the cases with ductal carcinoma in situ are not included in the study of Colleran et al. [1]. After carefully studying the data presented by Chen et al. [2], the data that we have retrieved for 9A/9A, 9A/6A, 6A/6A in cases were 92, 23, 0, respectively. Second, using the same search strategy and end-ofsearch date as those of Colleran et al. [1], we have located two relevant case–control studies in Pubmed with a total of 738 breast cancer cases and 624 controls [3], which have not been included in the meta-analysis even though they satisfied the search criteria. Specifically, the study by Dr Kenneth Offit [3] has provided separate data on TGFBR1 genotype: the number for 9A/9A, 9A/6A, 6A/6A in breast cancer cases and controls were 391, 67, 4 and 291, 38, 1, respectively. Third, one previous meta-analysis including seven studies have reported the role of the TGFBR1*6A/9A polymorphism and breast risk [4]. Following this metaanalysis, several colleagues have shared their data from unpublished case–control studies. Then, they performed a further meta-analysis and found TGFBR1*6A carriers have a 38% increased risk of breast cancer (OR 1.38, 95% CI 1.14–1.67) [3]. However, only one unpublished study provided by Dr Michael Reiss was concluded in the metaanalysis reported by Colleran et al. [1], which imply that the original odds ratios for the aforementioned studies may differ from those calculated by Colleran et al. [1]. Hence, the ongoing uncertainly still existed, and the conclusion by Colleran et al. [1] was not entirely credible. Despite the above, the results reported by Colleran et al. confirm the main results of genotype contrasts (9A/6A vs. 9A/9A, 6A/6A vs. 9A/9A, 9A/6A ? 6A/6A vs. 9A/9A, and 6A/6A vs. 9A/6A ? 9A/9A) for TGFBR1*6A/9A polymorphism compared with previous meta-analysis [3]. And the results are consistent with the findings provided by the recent meta-analysis by Liao et al. [5]. It is well-known that the TGFBR1 plays an important role in the TGFB singling pathway [6]. A number of studies have reported the role of TGFBR1*6A/9A polymorphism and breast cancer risk. And we believe that this remark will contribute to further, more accurate elaboration and substantiation of the original results presented by Colleran et al. [1]. Y. Zhang (&) College of Pharmacy, Jinan University, Guangzhou 510632, China e-mail: ebmmedicine@gmail.com

Association between the XRCC1 polymorphisms and thyroid cancer risk: a meta-analysis from case-control studies.

Background The previous published data on the association between the X-ray repair cross-conplementation group 1 (XRCC1) polymorphisms and thyroid cancer risk remained controversial. Hence, we performed a meta-analysis on all available studies that provided 1729 cases and 3774 controls (from 11 studies) for XRCC1 Arg399Gln, 1040 cases and 2487 controls for Arg194Trp (from 7 studies), and 1432 cases and 3356 controls for Arg280His (from 8 studies). Methodology/Principal Findings PubMed, CNKI, and EMBASE database were searched to identify relevant studies. Overall, no significant association was found between XRCC1 Arg399Gln (recessive model: OR = 0.95, 95% CI = 0.77–1.15; dominant model: OR = 0.89, 95% CI = 0.75–1.05; homozygote model: OR = 0.92, 95% CI = 0.69–1.23; Heterozygote model: OR = 0.91, 95% CI = 0.80–1.03; additive model: OR = 0.93, 95% CI = 0.81–1.07), Arg194Trp (recessive model: OR = 1.41, 95% CI = 0.62–3.23; dominant model: OR = 1.01, 95% CI = 0.77–1.34; homozygote model: OR = 1.42, 95% CI = 0.55–3.67; Heterozygote model: OR = 1.03, 95% CI = 0.85–1.26; additive model: OR = 1.08, 95% CI = 0.81–1.42), and Arg280His (recessive model: OR = 1.08, 95% CI = 0.56–2.10; dominant model: OR = 1.01, 95% CI = 0.84–1.22; homozygote model: OR = 1.00, 95% CI = 0.51–1.96; Heterozygote model: OR = 1.04, 95% CI = 0.75–1.42; additive model: OR = 1.03, 95% CI = 0.86–1.23) and thyroid cancer risk when all the eligible studies were pooled into the meta-analysis. In the further stratified and sensitivity analyses, significant association was still not found in these three genetic polymorphisms. Conclusions/Significance In summary, this meta-analysis indicates that XRCC1 Arg399Gln, Arg280His, and Arg194Trp are not associated with thyroid cancer.