Association of GSTO1 A140D and GSTO2 N142D Gene Variations with Breast Cancer Risk

Background: Polymorphisms in glutathione S-transferase (GST) genes may contribute to breast cancer risk. The aim of this study was to investigate any association of two common GSTO1 A140D and GSTO2 N142D gene polymorphisms with breast cancer risk in an Iranian population followed by a protein structure analysis. Materials and Methods: In the case-control study, 303 subjects comprising 153 women with breast cancer and 150 healthy controls were included. Genotypes of GSTO1 A140D and GSTO2 N142D polymorphisms were assessed by PCR-RFLP. Bioinformatics tools were employed to evaluate the damaging effects of A140D and N142D on the structures of GSTO1 and GSTO2 proteins. Results: Our genetic association study revealed that the GSTO1 A140D polymorphism was associated with breast cancer in a dominant model (OR= 1.75, 95%CI= 1.07-2.86, p= 0.026). Also, the A allele was significantly associated with breast cancer risk (OR= 1.69, 95%CI= 1.09-2.60, p= 0.018). With regard to the N142D polymorphism, there were significant associations between the GG genotype (OR= 2.20, 95%CI= 1.14-4.27, p= 0.019) and the G allele (OR= 1.47, 95%CI= 1.06-2.05, p= 0.021) and risk of breast cancer. Structural analysis revealed that A140D and N142D polymorphisms cause changes in both primary and secondary structures of GSTO1 and GSTO2, respectively. Conclusion: Based on our results, GSTO1 A140D and GSTO2 N142D polymorphisms could be genetic risk factors for breast cancer, but further studies with larger sample sizes focusing on different ethnicities are needed to obtain more comprehensive results.     

CYP2D6 and CYP2E1 Gene Polymorphisms and their Association with Cervical Cancer Susceptibility: A Hospital Based Case-Control Study from South-Western Maharashtra

Background: In last few years several studies all over the world discovered the genetic polymorphisms in different cytochrome P450 genes associated with risk of various cancers, but contradictory outcomes were evidenced in case of cervical cancer risk.  In this case-control study we aimed to see whether the polymorphism of CYP2D6 or CYP2E1 genes may or may not be associated with cervical cancer risk in women of rural Maharashtra. Methods: In this case-control study, the association of CYP2D6 and CYP2E1 gene polymorphism with cervical cancer risk was studied by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The study was conducted with 350 clinically confirmed cervical cancer patients and 350 healthy women in a population of South-Western Maharashtra. The Odds ratio (OR) with 95% confidence interval and p-value were evaluated, where p ≤0.005 was considered as statistically significant. Results: After the analysis of SNP (rs389209) of CYP2D6 and SNPs (rs2031920, rs6413432, rs6413420) of CYP2E1, we noticed that variant allele A of CYP2E1*6 showed significant increase in cervical cancer cases (OR=4.81; 95% CI: 1.57- 14.77; p=0.005). The genotypic distribution of heterozygote G/A genotype of CYP2D6*4 showed negative association with cervical cancer development when age of cancer occurrence (OR=0.41; 95% CI: 0.27- 0.61; p<0.0001) and tobacco history (OR=0.35; 95% CI: 0.20- 0.59; p=0.0001) was considered. Conclusion: The findings from this study supported that rs6413432 SNP of CYP2E1*6 increased cervical cancer risk in the studied rural women population.     

Relationship between LAPTM4B gene polymorphism and susceptibility of colorectal and esophageal cancers.

BACKGROUND: Lysosome-associated protein transmembrane 4 beta (LAPTM4B) is a novel gene of the mammalian LAPTM family and has been shown to be overexpressed in human hepatocellular carcinoma. There are two alleles, LAPTM4B*1 and *2, which share the same sequence except for one segment of 19 bp in the 5' untranslated region of the exon 1. LAPTM4B*1 has one 19 bp segment, while LAPTM4B*2 has two tight tandem segments. The current case-control study was aimed to identify relationship between the gene polymorphism of LAPTM4B and the susceptibility of colorectal and esophageal cancers. PATIENTS AND METHODS: Blood samples were collected from patients with colon, rectal or esophageal cancers and control subjects. Genotypes of LAPTM4B were determined by PCR to detect differences between cancer cases (n = 701) and healthy controls (n = 350). Association between the LAPTM4B polymorphism and the risk of cancer was calculated by unconditional logistic regression models. RESULTS: We found that there was a significant difference (P = 0.0016) in allelic frequencies of LAPTM4B*2 between colon cancer cases (33.2%) and controls (24.1%). The risk of colon cancer was elevated significantly in cases with *1/2 genotype [odds ratio (OR) = 1.474; 95% confidence interval (CI) = 1.037-2.095] and *2/2 genotype (OR = 2.531; 95% CI = 1.316-4.868) when compared with the *1/1 genotype. No significant difference was observed for LAPTM4B*2 between the rectal or esophageal cancer cases when compared with the controls. The polymorphism in LAPTM4B was associated with increased risk of colon cancer but not of rectal and esophageal cancers. CONCLUSIONS: These results indicate that the genetic polymorphism of LAPTM4B is a potential risk factor for the development of colon cancer.     

Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case-control study of Chinese women

BACKGROUND: Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma. METHODS: The authors evaluated common polymorphisms in the CYP1A1 gene in relation to breast carcinoma risk in a large population-based case-control study among Chinese women, the Shanghai Breast Cancer Study. Because the CYP1A1*3 and CYP1A1*4 alleles were not detected in the study population, analyses were performed for CYP1A1*2A (T-->C transition in the 3' noncoding region) and CYP1A1*2C (A-->G transition in exon 7, resulting in a substitution of Val for Ile) in 1134 patients with breast carcinoma and 1227 controls. RESULTS: The frequencies of the variant allele were 38.3% and 38.8% among cases and controls (P = 0.91), respectively, for the CYP1A1*2A polymorphism, and 23.1% and 24.8% (P = 0.26) for the CYP1A1*2C polymorphism. Homozygosity for both variant alleles in these 2 polymorphic sites (CYP1A1*2B) was associated with a borderline significant odds ratio (OR) of 0.71 (95% confidence interval [CI], 0.47-1.06). The reduced risk was more pronounced among postmenopausal women with long duration (> 30 yrs) of menstruation (OR = 0.43; 95% CI, 0.19-0.99) or among women with a low waist-to-hip ratio (OR = 0.52; 95% CI, 0.28-0.94). CONCLUSIONS: Results from the current study suggest that homozygosity for the CYP1A1*2A and CYP1A1*2C alleles in the CYP1A1 gene may be associated with a reduced risk for breast carcinoma, particularly among lean women with long-term endogenous estrogen exposure.     

The VEGF_936_C>T 3'UTR polymorphism reduces BRCA1-associated breast cancer risk in Polish women

The vascular endothelial growth factor (VEGF) plays a crucial role in the initiation of angiogenesis, which is an important stage in tumor development. A functional 936_C>T polymorphism in the VEGF gene and its association with sporadic breast cancer risk has been analyzed in various studies yielding conflicting results. To analyze the role of this polymorphism in modifying hereditary breast and ovarian cancer risks, we conducted a case-control study and genotyped 755 Polish BRCA1 carriers, including 319 breast cancer cases, 146 ovarian cancer cases, and 290 unaffected controls. The results revealed an association of the CT+TT genotypes with a reduced breast cancer risk (OR(adj) 0.63, 95% CI, 0.41-0.98; OR(clustered) 0.63, 95% CI, 0.48-0.83), and a potential effect on ovarian cancer risk (OR(adj) 0.62, 95% CI, 0.33-1.18; OR(clustered) 0.62, 95% CI, 0.47-0.83). Thus, the 936_C>T polymorphism appears to modify disease risks in BRCA1 carriers.     

Significant association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma: a meta-analysis

Many studies were published to examine the association between XRCC3 C241T polymorphism and hepatocellular carcinoma risk, but their results were inconsistent. To assess the association between XRCC3 C241T polymorphism and hepatocellular carcinoma risk more precisely, a meta-analysis was performed. PubMed, Embase and Wanfang databases were searched for relevant case–control studies. Data were extracted, and the pooled odds ratios (OR) with 95 % confidence intervals (95 % CI) were calculated. Finally, seven studies comprising 2,288 cases with hepatocellular carcinoma and 3,249 controls were included into the meta-analysis. Overall, there was an obvious association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma (TT versus CC: OR?=?3.31, 95 % CI 1.52–7.19, P?=?0.003; TT versus CC/CT: OR?=?3.31, 95 % CI 1.81–6.06, P?<?0.001). After adjusting for heterogeneity, there was still an obvious association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma (TT versus CC: OR?=?1.92, 95 % CI 1.13–3.26, P?=?0.016; TT versus CC/CT: OR?=?2.10, 95 % CI 1.25–3.55, P?=?0.005). Overall, there is a significant association between XRCC3 C241T polymorphism and increased risk of hepatocellular carcinoma. Further studies are needed to further assess the association in Caucasians.     

Association of rs2233678 and rs2233679 polymorphisms in the PIN1 gene with cancer risk: a meta-analysis

To data, epidemiological studies have assessed the association between peptidyl-propyl-cis/trans isomerase 1 (PIN1) gene polymorphisms and cancer risk, including breast cancer, hepatocellular carcinoma, lung cancer, esophageal cancer, head and neck squamous cell carcinoma, and laryngeal squamous cell cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs2233678 and rs2233679) of PIN1 gene and cancer risk by conducting a meta-analysis of case–control studies. A total of seven publications were included in this meta-analysis for both rs2233678 and rs2233679. Overall, rs2233678 polymorphism was found to be associated with decreased cancer risk in four genetic models (C-allele vs. G-allele: odd ratio (OR)?=?0.73, 95 % confidence interval (CI): 0.60–0.88; CC vs. GG: OR?=?0.55, 95 % CI: 0.36–0.84; CC+CG vs. GG: OR?=?0.72, 95 % CI 0.58–0.90; CC vs. CG+GG: OR?=?0.58, 95 % CI 0.38–0.89). However, the rs2233679 polymorphism of PIN1 gene did not appear to have an influence on caner susceptibility. In the subgroup analysis by cancer type, we observed that the PIN1 rs2233678 polymorphism was significantly associated with decreased breast cancer risk (C-allele vs. G-allele: OR?=?0.73, 95 % CI: 0.60–0.89; CC+CG vs. GG: OR?=?0.71, 95 % CI 0.57–0.89). Further subgroup analyses showed that the PIN1 rs2233678 polymorphism was associated with decreased cancer risk among Asian people (C-allele vs. G-allele: OR?=?0.63, 95 % CI: 0.51–0.79; CC vs. GG: OR?=?0.44, 95 % CI: 0.25–0.80; CC+CG vs. GG: OR?=?0.63, 95 % CI 0.50–0.79; CC vs. CG+GG: OR?=?0.47, 95 % CI 0.26–0.86). In conclusion, PIN1 rs2233678 polymorphism might be a potential biomarker for cancer risk among Asians, especially for breast cancer. Further large and well-designed studies are needed to confirm this conclusion.     

Genetic susceptibility to breast cancer in French-Canadians: role of carcinogen-metabolizing enzymes and gene-environment interactions

Breast cancer is the most frequent malignancy among women. Since genetic factors such as BRCA1 and BRCA2 as well as reproductive history constitute only 30% of the cause, environmental exposure may play a significant role in the development of breast cancer. Likewise, the relevant enzymes involved in the biotransformation of xenobiotics (from tobacco smoke, diet or other environmental sources) might play a role in breast carcinogenesis. Since individuals with modified ability to metabolize these carcinogens could have a different risk for breast cancer, we investigated the role of cytochromes P-450 (CYP1A1, CYP2D6), glutathione-S-transferases (GSTM1, GSTT1, GSTP1) and N-acetyltransferases (NAT1, NAT2) gene variants in breast carcinogenesis. A case-control study was conducted on 149 women with breast carcinoma and 207 healthy controls, both of French-Canadian origin. The CYP1A1*4 allele was found to be a significant risk determinant of breast carcinoma (OR = 3.3, 95% CI 1.1-9.7), particularly among post-menopausal women (OR = 4.0, 95% CI 1.2-13.8). The frequency of NAT2 rapid acetylators was increased among smokers (OR = 2.6, 95% CI 0.8-8.2), while the NAT1*10 allele conferred a 4-fold increase in risk among women who consumed well-done meat (OR = 4.4, 95% CI 1.0-18.9). These data suggest that CYP1A1*4, NAT1 and NAT2 variants are involved in the susceptibility to breast carcinoma by modifying the impact of exogenous and/or endogenous exposures.     

Cyclin D1 G870A polymorphism and breast cancer risk: a meta-analysis involving 23,998 subjects

Cyclin D1 (CCND1) plays an essential role in tumor development and progression through regulating the cell transition from G1 to the proliferative S phase. The CCND1 G870A polymorphism has been associated with an increased susceptibility to squamous cell carcinoma of the head and neck, bladder, prostate, and gastric cardiac cancers. There are a number of studies that explored the relationship between CCND1 G870A polymorphism and breast cancer risk, with inconsistent conclusions. In order to better define the predictive value of CCND1 G870A polymorphism in breast cancer, we searched PubMed and EBSCO for relevant publications. A total of 13 studies were indentified, which included 11,235 cases and 12,763 controls. We calculated the summary odds ratios and the corresponding 95% confidence interval. Our meta-analysis showed that carriers of AA genotype have a significantly higher risk in developing breast cancer compared with that of GG genotype (OR = 1.08, 95% CI = 1.01-1.17, p > = 0.03) in overall population. Furthermore, in subgroup analysis, CCND1 G870A polymorphism was associated with a marginally increased risk of breast cancer for Chinese compared to Caucasian populations with an OR = 1.14, 95% CI = 1.00-1.20, p-trend = 0.06 for AA + GA versus GG, if the controls were hospital-based population with an OR = 1.21, 95% CI = 0.99-1.47, p = 0.06 for AA versus GG and if the distributions of genotypes in control groups were consistent with the Hardy-Weinberg equilibrium (HWE) with an OR = 1.08, 95% CI = 1.00-1.15, p = 0.04 for AA versus GA + GG. Our meta-analysis represents the largest study to date indicating that the G870A polymorphism in CCND1 confers an increased risk for breast cancer. Further studies are warranted to explore the preventive measures to detect and manage the breast cancers attributable to the G870A polymorphism.     

Association between vitamin D receptor gene Cdx2 polymorphism and breast cancer susceptibility

Vitamin D receptor (VDR) gene polymorphisms have been reported to influence susceptibility to breast cancer. However, published findings on the association between VDR Cdx2 polymorphism and breast cancer susceptibility are conflicting. To get a precise estimation of the association between VDR Cdx2 polymorphism and breast cancer susceptibility, we conducted a meta-analysis of four case–control studies with a total of 8,880 subjects (3,841 cases and 5,039 controls). The results showed that VDR Cdx2 polymorphism was not associated with risk of breast cancer (A versus G: OR?=?0.96, 95 % CI 0.84–1.09; AA versus GG: OR?=?0.97, 95 % CI 0.64–1.45; AA/GA versus GG: OR?=?0.94, 95 % CI 0.80–1.10; AA versus GG/GA: OR?=?0.99, 95 % CI 0.65–1.51). Subgroup analysis in Caucasians also showed that VDR Cdx2 polymorphism was not associated with risk of breast cancer in Caucasians. However, there was a significant association in Africans (A versus G: OR?=?0.75, 95 % CI 0.60–0.94; AA versus GG: OR?=?0.53, 95 % CI 0.29–0.99; AA/GA versus GG: OR?=?0.75, 95 % CI 0.57–0.97). Therefore, the association between VDR Cdx2 polymorphism and breast cancer susceptibility is only found in Africans. More studies are needed to further assess the association in Asians or Africans.     

The AURKA Gene rs2273535 Polymorphism Contributes to Breast Carcinoma Risk - Meta-analysis of Eleven Studies

The rs2273535 polymorphism in the AURKA gene had proven to be associated with breast carcinoma susceptibility. Nevertheless, the results of different studies remain contradictory. A meta-analysis covering 28, 789 subjects from eleven different studies was here carried out in order to investigate the association in detail. The random effects model was used to analyze the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). A significant relationship between the rs2273535 polymorphism and breast tumors was found in an allelic genetic model (OR: 1.076, 95% CI: 1.004-1.153, p=0.040,  Pheterogeneity=0.002). No significant association was detected in a homozygote model (OR: 1.186, 95% CI: 0.990-1.423, P=0.065, Pheterogeneity=0.002), a heterozygote model (OR: 1.016, 95% CI: 0.959-1.076, p=0.064, Pheterogeneity=0.000), a dominant genetic model (OR: 1.147, 95% CI: 0.992-1.325, p=0.217, Pheterogeneity=0.294) and a recessive genetic model (OR: 1.093, 95% CI: 0.878-1.361, p=0.425, Pheterogeneity=0.707). A significant relationship between the rs2273535 polymorphism in the AURKA gene and breast tumor in Asian group was found in an allelic genetic model (OR: 1.124, 95% CI: 1.003-1.29, p=0.044, Pheterogeneity=0.034), a homozygote model (OR: 1.229, 95% CI: 1.038-1.455, p=0.016, Pheterogeneity=0.266) and a recessive genetic model (OR: 1.227, 95% CI: 1.001-1.504, p=0.049, Pheterogeneity=0.006). A significant association was thus observed between the rs2273535 polymorphism in the AURKA gene and breast cancer risk. Individuals with the rs2273535 polymorphism in the AURKA gene have a higher risk of breast cancer in Asian populations, but not in Caucasians.     

Glutathione S-transferase M1 polymorphism and lung cancer risk in African-Americans

Glutathione S:-transferase M1 (GSTM1) can detoxify many carcinogens, including polycyclic aromatic hydrocarbons such as those from cigarette smoke. Though a number of studies have been published about the association between GSTM1 polymorphism and lung cancer, this association has received limited attention in the African-American population. We conducted a case-control study to investigate the role of GSTM1 polymorphism in the development of lung cancer in African-Americans. Specimens of DNA from 117 lung cancer cases and 120 controls were assayed for detection of GSTM1 genotype by polymerase chain reaction (PCR). The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene and other risk factors were estimated by logistic regression. Thirty-seven of the 117 cases (31. 6%) and 24 of the 120 controls (20.0%) had the GSTM1 null genotype; the OR was 2.10 (95% CI 1.07-4.11) after adjustment for age, gender and smoking. The association was higher for squamous cell carcinoma (OR 2.98, 95% CI 1.09-8.19) than for adenocarcinoma (OR 1.95, 95% CI 0.81-4.66). We observed a stronger association between GSTM1 null genotype and lung cancer among heavy smokers with > or =30 pack-years (OR 4.35, 95% CI 1.16-16.23). This association was also found in squamous cell carcinoma (OR 6.26, 95% CI 1.31-29.91). In the analysis combining GSTM1 polymorphism and smoking, smokers with the null genotype had high risk (OR 8.19, 95% CI 2.35-28.62) compared with non-smokers with the wild-type genotype, and the risk increased with smoking cigarette pack-years (P: = 0.0001 for trend). Our results suggest that GSTM1 polymorphism plays a role in the development of lung cancer and modifies the risk for smoking-related lung cancer in African-Americans.     

Association between XRCC1 Arg399Gln polymorphism and hepatitis virus-related hepatocellular carcinoma risk in Asian population

To investigate the association between X-ray repair cross-complementing group 1 (XRCC1) Arg399Gln polymorphism and hepatitis virus-related hepatocellular carcinoma risk, we performed a systematic meta-analysis of eligible case–control studies. Eligible studies were identified from the PubMed, Embase, and Chinese National Knowledge Infrastructure databases up to March 2013. The odds ratios (ORs) and corresponding 95 % confidence interval (95 % CI) of XRCC1 Arg399Gln polymorphism in hepatitis virus-related hepatocellular carcinoma cases compared with those in controls were calculated. The meta-analysis was performed using fixed-effect or random-effect methods according to the absence or presence of heterogeneity. This meta-analysis included 1,558 cases with hepatitis virus-related hepatocellular carcinoma and 1,338 controls. Meta-analysis of available data showed that there was no association between XRCC1 Arg399Gln polymorphism and risk of hepatitis virus-related hepatocellular carcinoma under all contrast models (Gln vs. Arg: fixed-effect OR?=?0.92, 95 % CI 0.82–1.04, P?=?0.18; GlnGln vs. ArgArg: random-effect OR?=?0.79, 95 % CI 0.50–1.25, P?=?0.32; GlnGln/ArgGln vs. ArgArg: fixed-effect OR?=?0.92, 95 % CI 0.79–1.07, P?=?0.28; and GlnGln vs. ArgArg/ArgGln: random-effect OR?=?0.83, 95 % CI 0.52–1.34, P?=?0.45). Sensitivity analysis further showed that there was no association between XRCC1 Arg399Gln polymorphism and risk of hepatitis B-related hepatocellular carcinoma under all contrast models (Gln vs. Arg: fixed-effect OR?=?0.93, 95 % CI 0.82–1.05, P?=?0.25; GlnGln vs. ArgArg: fixed-effect OR?=?0.86, 95 % CI 0.64–1.16, P?=?0.32; GlnGln/ArgGln vs. ArgArg: fixed-effect OR?=?0.93, 95 % CI 0.80–1.10, P?=?0.41; and GlnGln vs. ArgArg/ArgGln: fixed-effect OR?=?0.85, 95 % CI 0.63–1.13, P?=?0.26). Our meta-analysis of the available data did not find an obvious effect of XRCC1 Arg399Gln polymorphism on hepatitis-related hepatocellular carcinoma. More well-designed studies with large sample are needed to further verify the effect.     

Allele 2 of the interleukin-1 receptor antagonist gene (IL1RN*2) is associated with a decreased risk of primary lung cancer

IL-1 receptor antagonist (IL-1ra), a structural variant of IL-1, binds to the same IL-1 receptor and acts as a competitive inhibitor of IL-1 bioactivity. IL-1ra protein has been widely investigated and found to be associated with different human malignancies. In the second intron of the IL-1RN gene, there is a functional polymorphism of a variable number of tandem repeats (VNTR), which is characterized as having an importance role in regulating the serum IL-1ra levels, human immune response and cancer risk. We genotyped this VNTR of IL-1RN in a case-control study of 885 histologically confirmed lung cancer patients and 1024 cancer-free controls frequency-matched to the cases on age and sex in a Chinese population to evaluate the association of this variant and lung cancer risk. We found that the presence of the allele 2 of IL-1RN (IL-RN*2) was associated with a 32% significantly decreased risk of lung cancer (adjusted OR, 0.68; 95% CI, 0.52-0.89). Stratified analyses revealed that the reduced risks associated with the genotypes with IL-RN*2allele (I/II and II/II) were more evident in non-smokers (adjusted OR, 0.53; 95% CI, 0.35-0.79) and in subjects with squamous cell carcinoma (adjusted OR, 0.49; 95% CI, 0.31-0.76). These findings support our priori hypothesis that the IL1RN*2 allele may contribute to lung cancer risk in the Chinese population. More functional data for this IL1RN polymorphism are warranted to explore its role in lung carcinogenesis.     

Case-control study and meta-analysis of SULT1A1 Arg213His polymorphism for gene, ethnicity and environment interaction for cancer risk

Cytosolic sulphotransferase SULT1A1 plays a dual role in the activation of some carcinogens and inactivation of others. A functional polymorphism leading to Arg(213)His substitution (SULT1A1*2) affects its catalytic activity and thermostability. To study the association of SULT1A1*2 polymorphism with tobacco-related cancers (TRCs), a case-control study comprising 132 patients with multiple primary neoplasm (MPN) involving TRC and 198 cancer-free controls was carried out. One hundred and thirteen MPN patients had at least one cancer in upper aerodigestive tract including lung (UADT-MPN). SULT1A1*2 showed significant risk association with UADT-MPN (odds ratio (OR)=5.50, 95% confidence interval (CI): 1.09, 27.7). Meta-analysis was conducted combining the data with 34 published studies that included 11 962 cancer cases and 14 673 controls in diverse cancers. The SULT1A1*2 revealed contrasting risk association for UADT cancers (OR=1.62, 95% CI: 1.12, 2.34) and genitourinary cancers (OR=0.73, 95% CI: 0.58, 0.92). Furthermore, although SULT1A1*2 conferred significant increased risk of breast cancer to Asian women (OR=1.91, 95% CI: 1.08, 3.40), it did not confer increased risk to Caucasian women (OR=0.92, 95% CI: 0.71, 1.18). Thus risk for different cancers in distinct ethnic groups could be modulated by interaction between genetic variants and different endogenous and exogenous carcinogens.     

Risk Factor Analysis for Breast Cancer in Premenopausal and Postmenopausal Women of Punjab,India

Objective: Amritsar, the second largest town of agrarian state of Punjab, India reports high number of breast cancer cases every year. The present study investigated the etiology of breast cancer using various obesity indices and other epidemiological factors among breast cancer patients residing in and around Amritsar city. Methods: In this case control study, risk factors for breast cancer were analyzed in 542 female subjects: 271 females with breast cancer patients and 271 unrelated healthy females matched for age as control females. Results: Bivariate analysis for risk factors in cases and controls showed a lower risk (OR=0.65, 95% CI 0.43-0.99, p=0.04) in obese cases with BMI≥25kg/m2 as compared to subjects with normal BMI. Risk factor analysis showed that parameter which provided risk for cancer in postmenopausal women was obesity and in premenopausal women was parity. Postmenopausal women with BMI (overweight: OR=0.39, 95% CI 0.17-0.92, p=0.03; obese: OR= 0.26, 95% CI 0.13-0.52, p=0.00), WC (OR=0.17, 95% CI 0.05-0.52, p=0.00) and WHtR (p=0.02) had highr risk. Premenopausal women with 3 or less than 3 children had a higher risk (OR=5.54, 95 % CI 2.75-11.19, p=0.00) than postmenopausal women when compared to women with more than 3 children. Binary logistic regression analysis revealed that low parity (≤3) substantially increased the risk for breast cancer (OR=4.80, 95% CI 2.34-9.85, p=0.00) in premenopausal women. Conclusion: Obesity, parity associated breast cancer risk and reduced breastfeeding cumulatively predispose the premenopausal women of this region to higher risk of breast cancer.     

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism is Associated with Breast Cancer Risk: A Meta-Analysis

Background: A number of case-control studies were conducted to investigate the association of angiotensinconverting enzyme insertion/deletion (ACE I/D) polymorphism with breast cancer. But the results remain controversial.This meta-analysis aims to comprehensively evaluate the association of ACE I/D polymorphism with breast cancer.Method: A comprehensive literature search on PubMed, Google Scholar, SCOPUS and ISI Web of Knowledgedatabases for studies published up to June 01, 2018 was performed. Summary odds ratios (ORs) and 95% confidenceintervals (CI) were estimated. Publication bias of literatures was evaluated using funnel plots and Egger’s test. Results:A total of 20 studies including 2846 breast cancer cases 9299 controls meeting the predefined criteria were involved inthe meta-analysis. Overall, the ACE I/D polymorphisms was significantly associated with breast cancer under the allelemodel (I vs. D: OR= 0.803, 95% CI 0.647-0.996, p=0.046), the homozygote model (II vs. DD: OR= 0.662, 95% CI0.462-0.947, p=0.024), the heterozygote model (ID vs. DD: OR= 0.707, 95% CI 0.528-0.946, p=0.020), the dominantmodel (II+ID vs. DD: OR= 0.691, 95% CI 0.507-0.941, p=0.019). In the subgroup analysis by ethnicity, a significantassociation was found among Asian and Caucasian populations, but not among mixed populations. Conclusions: Thismeta-analysis suggests that ACE I/D polymorphism may be associated with increased risk of breast cancer, especiallyamong Asian and Caucasians. However, well-designed studies with larger sample size and more ethnic groups areneeded to further validate the results.     

NFKB1 -94 insertion/deletion polymorphism and cancer risk: a meta-analysis

Previous studies on the associations of the NFKB1 -94 insertion/deletion polymorphism with cancer risk have produced conflicting results. The purpose of this meta-analysis is to define the effect of the NFKB1 -94 insertion/deletion polymorphism on cancer risk. A search of the literature by PubMed was performed to identify studies based on the predetermined inclusion criteria. Twenty-three studies consisting of 6,494 cases and 9,884 controls were identified and analyzed. Overall, significant association was observed between the polymorphism and cancer risk under all genetic models. Subgroup analysis according to ethnicity and cancer type also detected significant association. The NFKB1 -94 insertion/deletion polymorphism was associated with cancer risk in Asian population (dominant model: OR?=?1.52, 95 % CI?=?1.17–1.98; recessive model: OR?=?1.50, 95 % CI?=?1.26–1.79; II vs. DD: OR?=?1.90, 95 % CI?=?1.37–2.65; ID vs. DD: OR?=?1.32, 95 % CI?=?1.05–1.66; I vs. D: OR?=?1.37, 95 % CI?=?1.17–1.60), but not in Caucasian population. In addition, significant associations in OC, HCC, and OSCC were observed, but significant associations were not found in BC and LC. The current meta-analysis suggested that NFKB1 -94 insertion/deletion polymorphism may influence cancer risk in Asian population.     

The association between ATM D1853N polymorphism and breast cancer susceptibility: a meta-analysis

Background

Emerging evidence suggests that ataxia telangiectasia-mutated (ATM) is involved in numerous damage repair signaling pathways and cell-cycle checkpoints. Heterozygous carriers of ATM-mutations have an increased risk for the development of breast cancer. The purpose of this study is to evaluate the association between ATM exon39 5557G > A (D1853N, rs1801516) polymorphism and breast cancer susceptibility with the use of a meta-analysis.

Methods

By searching PubMed and Embase databases, a total of 9 epidemiological studies with 4,191 cases and 3,780 controls were identified. Crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for ATM D1853N polymorphism and breast cancer risk were calculated using fixed- or random-effects model based on the degree of heterogeneity among studies.

Results

No significant association between the ATM D1853N polymorphism and breast cancer risk was observed in overall analysis (GA versus GG: OR = 1.18; 95% CI, 0.90-1.53; AA versus GG: OR = 0.77; 95% CI, 0.58-1.03; dominant model: OR = 1.16; 95% CI, 0.89-1.51; and recessive model: OR = 0.78; 95% CI, 0.59-1.04, respectively).

Conclusion

Our results indicate that ATM D1853N polymorphism is not a risk factor for developing breast cancer.