scholarly journals MNGI-12. PLEIOTROPIC MLLT10 VARIATION CONFERS RISK OF MENINGIOMA, BREAST, AND OVARIAN CANCERS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi142-vi142
Author(s):  
Kyle Walsh ◽  
Chenan Zhang ◽  
Lisa Calvocoressi ◽  
Helen Hansen ◽  
Andrew Berchuck ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Risk Allele ◽  
Meta Analysis ◽  
Ovarian Cancer Risk ◽  
Genome Wide Association Studies ◽  
Ovarian Cancers ◽  
Genome Wide ◽  
Increased Risk

Abstract BACKGROUND Women ages 35–44 have three-fold higher risk of meningioma compared to men. Epidemiologic studies have implicated exogenous hormone use, but endogenous hormonal factors are inconsistently associated. Elevated body mass index (BMI) is consistently associated with meningioma risk in both men and women, and personal history of breast cancer has also been associated with meningioma risk. Recent genome-wide association studies (GWAS) have identified a meningioma risk locus on chromosome 10p12 near previous GWAS hits for breast and ovarian cancers. METHODS To elucidate the pleiotropic role of 10p12 variation in predisposition to diverse tumors - possibly via a common mediating factor - we performed imputation‐based fine‐mapping in three case-control datasets of meningioma (927 cases, 790 controls), female breast cancer (28108 cases, 22209 controls), and ovarian cancer (25509 cases, 40941 controls). Analyses were stratified by sex (meningioma), estrogen receptor status (breast), and histotype (ovarian), then combined using ASSET meta-analysis. Lead variants were queried for association with >700 additional traits to identify potential effect-mediators. RESULTS Two-sided ASSET meta-analysis identified a lead variant near the MLLT10 promoter (P=1.4x10-13) associated with significantly increased risk of meningioma in women (OR=1.42, 95% CI: 1.20–1.69) and non-significantly increased risk in men (OR=1.19, 95% CI: 0.91–1.57). The meningioma risk allele was also associated with ovarian cancer risk (OR=1.09, 95% CI: 1.06–1.12) and ER+ breast cancer risk (OR=1.05, 95% CI: 1.02–1.08), but protected against ER- breast cancer (OR=0.91, 95% CI: 0.86–0.96). The risk allele was associated with higher body fat percentage, waist circumference and BMI at genome-wide levels (P< 5.0x10-8), but mediation analysis adjusting for BMI did not attenuate its association with meningioma risk. CONCLUSION We identify a MLLT10 eQTL that confers risk of female meningioma, ER+ breast cancer, ovarian cancer, and obesity, but which protects against ER- breast cancer. Our results implicate a possible estrogenic mechanism underlying meningioma tumorigenesis.

scholarly journals The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case–control studies

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Weiqing Liu ◽  
Shumin Ma ◽  
Lei Liang ◽  
Zhiyong Kou ◽  
Hongbin Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Thyroid Cancer ◽  
Cancer Risk ◽  
Large Scale ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Cancer Type ◽  
Increased Risk ◽  
Risk Of Cancer

Abstract Background Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

scholarly journals Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome–wide interaction study

2013 ◽  
Vol 20 (6) ◽  
pp. 875-887 ◽  
Author(s):  
Anja Rudolph ◽  
Rebecca Hein ◽  
Sara Lindström ◽  
Lars Beckmann ◽  
Sabine Behrens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fixed Effects ◽  
Association Studies ◽  
Meta Analysis ◽  
Case Control ◽  
Genome Wide Association Studies ◽  
Genetic Modifiers ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk

Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case–control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) <3.0×10−3 were selected for replication using pooled case–control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 controls. Fixed-effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−6), two SNPs in SLC25A21 (combined Pint≤4.8×10−5), and three SNPs in PLCG2 (combined Pint≤4.5×10−5). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−5), one SNP in CD80 (combined Pint≤8.2×10−6), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−6), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−5). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling, and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies.

scholarly journals The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case-control studies

2021 ◽  
Author(s):  
Weiqing Liu ◽  
Shumin Ma ◽  
Lei Liang ◽  
Zhiyong Kou ◽  
Hongbin Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Thyroid Cancer ◽  
Cancer Risk ◽  
Large Scale ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Cancer Type ◽  
Increased Risk ◽  
Risk Of Cancer

Abstract Background: Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods: PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results: XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG+AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion: This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

scholarly journals Endometriosis and cancer: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Marina Kvaskoff ◽  
Yahya Mahamat-Saleh ◽  
Leslie V Farland ◽  
Nina Shigesi ◽  
Kathryn L Terry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cervical Cancer ◽  
Cancer Risk ◽  
Cohort Studies ◽  
Publication Bias ◽  
Meta Analysis ◽  
Case Control ◽  
Risk Of Bias ◽  
Ovarian Cancer Risk

Abstract BACKGROUND Endometriosis is an often chronic, inflammatory gynaecologic condition affecting 190 million women worldwide. Studies have reported an elevated cancer risk among patients with endometriosis. However, prior research has included methodologic issues that impede valid and robust interpretation. OBJECTIVE AND RATIONALE We conducted a meta-analysis of studies investigating the association between endometriosis and cancer risk and analysed the results by methodologic characteristics. We discuss the implications of cancer screening in patients and management challenges faced by clinicians. SEARCH METHODS We searched PubMed and Embase databases for eligible studies from inception through 24 October 2019. We included cohort and case-control studies examining the association between endometriosis and cancer risk; cross-sectional studies and case reports were excluded. Publications had to present risk/rate/odds estimates with 95% CI. Random effects meta-analysis was used to estimate summary relative risks (SRR) and CIs. Heterogeneity across studies was assessed by the Q test and I2 statistics, and publication bias using Egger's and Begg's tests. Risk of bias and quality of the included studies were assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. OUTCOMES Forty-nine population-based case-control and cohort studies were included. Twenty-six studies were scored as having a ‘serious’/‘critical’ risk of bias, and the remaining 23 ‘low’/‘moderate’. Cancer-specific analyses showed a positive association between endometriosis and ovarian cancer risk (SRR = 1.93, 95% CI = 1.68–2.22; n = 24 studies) that was strongest for clear cell (SRR = 3.44, 95% CI = 2.82–4.42; n = 5 studies) and endometrioid (SRR = 2.33, 95% CI = 1.82–2.98; n = 5 studies) histotypes (Pheterogeneity &lt; 0.0001), although with significant evidence of both heterogeneity across studies and publication bias (Egger’s and Begg’s P-values &lt; 0.01). A robust association was observed between endometriosis and thyroid cancer (SRR = 1.39, 95% CI =1.24–1.57; n = 5 studies), a very small association with breast cancer (SRR = 1.04, 95% CI =1.00–1.09; n = 20 studies) and no association with colorectal cancer (SRR = 1.00, 95% CI =0.87–1.16; n = 5 studies). The association with endometrial cancer was not statistically significant (SRR = 1.23, 95% CI =0.97–1.57; n = 17 studies) overall and wholly null when restricted to prospective cohort studies (SRR = 0.99, 95% CI =0.72–1.37; n = 5 studies). The association with cutaneous melanoma was also non-significant (SRR = 1.17, 95% CI =0.97–1.41; n = 7 studies) but increased in magnitude and was statistically significant when restricted to studies with low/moderate risk of bias (SRR = 1.71, 95% CI = 1.24–2.36, n = 2 studies). The most robust finding both in terms of statistical significance and magnitude of effect was an inverse association with cervical cancer (SRR = 0.68, 95% CI =0.56–0.82; n = 4 studies); however, this result has a high potential to reflect heightened access to detection of dysplasia for women who reached an endometriosis diagnosis and is thus likely not causal. Several additional cancer types were explored based on &lt;4 studies. WIDER IMPLICATIONS Endometriosis was associated with a higher risk of ovarian and thyroid, and minimally (only 4% greater risk) with breast cancer, and with a lower risk of cervical cancer. However, this meta-analysis confirms that: a majority of studies had severe/critical risk of bias; there is impactful heterogeneity across studies—and for ovarian cancer, publication bias; and causal inference requires temporality, which in many studies was not considered. We discuss the implications of these potential associations from the perspectives of patients with endometriosis, clinicians involved in their care, and scientists investigating their long-term health risks.

Glutathione S-transferase M1, T1, and P1 Polymorphisms and Ovarian Cancer Risk: A Meta-Analysis

2010 ◽  
Vol 20 (5) ◽  
pp. 732-737 ◽  
Author(s):  
Konstantinos P. Economopoulos ◽  
Theodoros N. Sergentanis ◽  
Nikos F. Vlahos
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Confidence Interval ◽  
Random Effects ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Ovarian Cancer Risk ◽  
Case Control Studies ◽  
Increased Risk ◽  
Gstp1 Ile105val

Introduction:Cytosolic glutathione S-transferase (GST) comprises multiple isoenzymes that catalyze reactions between glutathione and lipophilic compounds with electrophilic centers, resulting in the neutralization of toxic compounds, xenobiotics, and products of oxidative stress. Several studies have examined whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, and GSTP1 Ile105Val) represent risk factors for ovarian cancer, as they all may denote reduced enzyme activity. This meta-analysis aimed to examine the associations between the aforementioned polymorphisms and ovarian cancer risk.Methods:The MEDLINE database was searched up to September 2009 using the appropriate terms. Case-control studies with no mutually overlapping populations were selected. Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Meta-regression with publication year was also performed.Results:Eight studies regarding GSTM1 null polymorphism status (2357 cases and 3044 controls), 6 studies concerning GSTT1 null polymorphism (1923 cases and 2759 controls), and 3 studies on GSTP1 Ile105Val were included in the meta-analysis. The GSTM1 null genotype was not associated with an increased risk for ovarian cancer (pooled OR, 1.031; 95% confidence interval, 0.867-1.226; random effects). The GSTT1 null genotype was not associated with an increased ovarian cancer risk (pooled OR, 0.934; 95% confidence interval, 0.804-1.086; random effects); similarly, no significant associations were demonstrated for GSTP1 Ile105Val.Conclusions:The examined GSTM1, GSTT1, and GSTP1 genotype polymorphisms do not seem to confer any additional risk for ovarian cancer. Given that the studies included in this meta-analysis involve mainly white populations, these results cannot be extrapolated on other populations, and additional data are needed for future race-specific analyses.

Oral Contraceptives and Risk of Ovarian Cancer and Breast Cancer Among High-Risk Women: A Systematic Review and Meta-Analysis

2013 ◽  
Vol 31 (33) ◽  
pp. 4188-4198 ◽  
Author(s):  
Patricia G. Moorman ◽  
Laura J. Havrilesky ◽  
Jennifer M. Gierisch ◽  
Remy R. Coeytaux ◽  
William J. Lowery ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Brca2 Mutation ◽  
Ovarian Cancer Risk ◽  
Mutation Carriers ◽  
History Of ◽  
Meta Analyses

Purpose To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. Methods We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. Results From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. Conclusion Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.

scholarly journals Identifying 31 novel breast cancer susceptibility loci using data from genome-wide association studies conducted in Asian and European women

2019 ◽  
Author(s):  
Xiang Shu ◽  
Jirong Long ◽  
Qiuyin Cai ◽  
Sun-Seog Kweon ◽  
Ji-Yeob Choi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Asian Populations ◽  
Risk Variants ◽  
Genome Wide ◽  
European Women

ABSTRACTCommon genetic variants in 183 loci have been identified in relation to breast cancer risk in genome-wide association studies (GWAS). These risk variants combined explain only a relatively small proportion of breast cancer heritability, particularly in Asian populations. To search for additional genetic susceptibility loci for breast cancer, we performed a meta-analysis of data from GWAS conducted in Asians (24,206 cases and 24,775 controls). Variants showing an association with breast cancer risk at P < 0.01 were evaluated in GWAS conducted in European women including 122,977 cases and 105,974 controls. In the combined analysis of data from both Asian and European women, the lead variant in 28 loci not previously reported showed an association with breast cancer risk at P < 5 ×10−8. In the meta-analysis of all GWAS data from Asian and European descendants, we identified SNPs in three additional loci in association with breast cancer risk at P < 5 ×10−8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). Expression quantitative trait locus (eQTL) and gene-based analyses provided evidence for the possible involvement of the YBEY, MAN2C1, SNUPN, TBX1, SEMA4A, STC1, MUTYH, LOXL2, and LINC00886 genes underlying the associations observed in eight of these 28 newly identified risk loci. In addition, we replicated the association for 78 of the 166 previously reported risk variants at P < 0.05 in women of Asian descent using GWAS data. These findings improve our understanding of breast cancer genetics and etiology and extend to Asian populations previous findings from studies of European women.

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