Performance of Common Genetic Variants in Breast-Cancer Risk Models

Wacholder, Sholom; Hartge, Patricia; Prentice, Ross L.; García-Closas, Montserrat; Feigelson, Heather Spencer; Diver, W. Ryan; Thun, Michael J.; Cox, David G.; Hankinson, Susan E.; Kraft, Peter; Rosner, Bernard; Berg, Christine D.; Brinton, Louise A.; Lissowska, Jolanta; Sherman, Mark E.; Chlebowski, Rowan T.; Kooperberg, Charles; Jackson, Rebecca D.; Buckman, Dennis W.; Hui, Peter; Pfeiffer, Ruth M.; Jacobs, Kevin B.; Thomas, Gilles; Hoover, Robert N.; Gail, Mitchell H.; Chanock, Stephen J.; Hunter, David J.

doi:10.1056/nejmoa0907727

Cited by 377 publications

(340 citation statements)

References 31 publications

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“…Risk factors for breast cancer include getting older,being overweight,using hormone replacement therapy (also called menopausal hormone therapy), taking birth control pills, drinking alcohol, not having children or having first child after age 35 or having dense breasts (Setiawan et al, 2009). In addition, genomewide association studies provide evidence that genetic factors are important in the pathogenesis of breast cancer (Wacholder et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Insertion/deletion (I/D) in the Angiotensin-converting Enzyme Gene and Breast Cancer Risk: Lack of Association in a Meta-analysis

Pei

Li²

2012

Asian Pacific Journal of Cancer Prevention

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Purpose: Breast cancer is an important cause of cancer-related death in women. Numerous studies have evaluated the association between the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and breast cancer risk. However, the specific association is still controversial rather than conclusive. Therefore, we performed a meta-analysis of related studies to address this controversy. Methods: PubMed, EMBASE, Google Scholar and the Chinese National Knowledge Infrastructure databases were systematically searched to identify relevant studies. A meta-analysis was performed to examine the association between the I/D polymorphism in the ACE gene and susceptibility to breast cancer. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results: 10 separate studies of 7 included articles with 10,888 subjects on the relation between the I/D polymorphism in the ACE gene and breast cancer were analyzed by meta-analysis, and our results showed no association between the I/D polymorphism in the ACE gene and breast cancer in total population and different populations. No publication bias was found in the present study. Conclusions: The ACE I/D polymorphism may not be associated with breast cancer risk. Further large and well-designed studies are needed to confirm this conclusion.

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Section: Introductionmentioning

confidence: 99%

Insertion/deletion (I/D) in the Angiotensin-converting Enzyme Gene and Breast Cancer Risk: Lack of Association in a Meta-analysis

Pei

Li²

2012

Asian Pacific Journal of Cancer Prevention

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“…8 Although recent genomewide association studies have successfully detected multiple variants with low-penetrance risk to BC, a panel of ten such SNPs only represents a predictive accuracy for BC of 59.7%. 6 Thus, the known environmental and genetic risk factors have limited utility in evaluating the risk of BC.…”

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confidence: 99%

DNA methylation array analyses identified breast cancer‐associated HYAL2 methylation in peripheral blood

Yang

Pfütze

Zucknick

et al. 2014

Intl Journal of Cancer

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Breast cancer (BC) is the leading cause of cancer-related mortality in women worldwide. Changes in DNA methylation in peripheral blood could be associated with malignancy at early stage. However, the BC-associated DNA methylation signatures in peripheral blood were largely unknown. Here, we performed a genome-wide methylation screening and identified a BC-associated differentially methylated CpG site cg27091787 in the hyaluronoglucosaminidase 2 gene (HYAL2) (discovery round with 72 BC case and 24 controls: p 5 2.61 3 10 29 adjusted for cell-type proportions). The substantially decreased methylation of cg27091787 in BC cases was confirmed in two validation rounds (first validation round with 338 BC case and 507 controls: p < 0.0001; second validation round with 189 BC case and 189 controls: p < 0.0001). In addition to cg27091787, the decreased methylation of a 650-bp CpG island shore of HYAL2 was also associated with increased risk of BC. Moreover, the expression and methylation of HYAL2 were inversely correlated with a p-value of 0.006. To note, the BC-associated decreased HYAL2 methylation was replicated in the T-cell fraction (p 5 0.034). The cg27091787 methylation level enabled a powerful discrimination of earlystage BC cases (stages 0 and I) from healthy controls [area under curve (AUC) 5 0.89], and was robust for the detection of BC in younger women as well (age < 50, AUC 5 0.87). Our study reveals a strong association between decreased HYAL2 methylation in peripheral blood and BC, and provides a promising blood-based marker for the detection of early BC.Breast cancer (BC) is the most common cancer and the leading cause of cancer-related mortality among women, 1 with 1.7 million new cases and 522,000 deaths in 2012. 2 In the United States, one in eight women will develop BC in her lifetime. 3 Although therapeutic advances have improved the survival rate, most BC patients still suffer from greatly

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“…Despite the wealth of dozens of genes and hundreds of SNPs, the effective size of the susceptibility to disease provided by each SNP is too small that has no clinical application [6] and most inherited risk remains unexplained [10]. Approximately 20-25% of heritability can be explained with current GWAS [10]; even efforts to combine these newly identified genetic variants with environmental factors and clinicopathologic characteristics have failed to predict the risk of diseases such as breast cancer [11].…”

Section: Facing the Realitymentioning

confidence: 99%

Genome diagnostics: next-generation sequencing, new genome-wide association studies and clinical challenges

Ziogas

Roukos

2011

Expert Review of Molecular Diagnostics

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Performance of Common Genetic Variants in Breast-Cancer Risk Models

Abstract: BACKGROUND-Genomewide association studies have identified multiple genetic variants associated with breast cancer. The extent to which these variants add to existing risk-assessment models is unknown.

Cited by 377 publications

References 31 publications

Insertion/deletion (I/D) in the Angiotensin-converting Enzyme Gene and Breast Cancer Risk: Lack of Association in a Meta-analysis

Insertion/deletion (I/D) in the Angiotensin-converting Enzyme Gene and Breast Cancer Risk: Lack of Association in a Meta-analysis

DNA methylation array analyses identified breast cancer‐associated HYAL2 methylation in peripheral blood

Genome diagnostics: next-generation sequencing, new genome-wide association studies and clinical challenges

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