Genetic Variation in Transforming Growth Factor Beta 1 and Mammographic Density in Singapore Chinese Women

Lee, Eunjung; Berg, David Van Den; Hsu, Chris; Ursin, Giske; Koh, Woon Puay; Yuan, Jian‐Min; Stram, Daniel O.; Yu, Mimi C.; Wu, Anna H.

doi:10.1158/0008-5472.can-12-1870

Cited by 14 publications

(9 citation statements)

References 43 publications

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“…This SNP has previously been associated with breast cancer risk in East Asian women [ 31 , 32 ], but not with mammographic density at a genome-wide significance level. The protein encoded by the TAB2 gene is an important mediator of interleukin-1 (IL-1)-induced activation of the NFkB and MAPK8/JNK pathway [ 33 ] which has been associated with early tumorigenesis and metastasis [ 34 , 35 ] as well as mammary development [ 36 ]. The TAB2 protein also interacts directly with the N-terminal domain of the estrogen receptor alpha (ESR1) and has been implicated in proinflammatory induced reactivation of repressed estrogen receptor (ER) signaling pathways [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of two novel mammographic density loci at 6Q25.1

Brand

Humphreys

et al. 2015

Breast Cancer Res

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IntroductionMammographic density (MD) is a strong heritable and intermediate phenotype for breast cancer, but much of its genetic variation remains unexplained. We performed a large-scale genetic association study including 8,419 women of European ancestry to identify MD loci.MethodsParticipants of three Swedish studies were genotyped on a custom Illumina iSelect genotyping array and percent and absolute mammographic density were ascertained using semiautomated and fully automated methods from film and digital mammograms. Linear regression analysis was used to test for SNP-MD associations, adjusting for age, body mass index, menopausal status and six principal components. Meta-analyses were performed by combining P values taking sample size, study-specific inflation factor and direction of effect into account.ResultsGenome-wide significant associations were observed for two previously identified loci: ZNF365 (rs10995194, P = 2.3 × 10−8 for percent MD and P = 8.7 × 10−9 for absolute MD) and AREG (rs10034692, P = 6.7 × 10−9 for absolute MD). In addition, we found evidence of association for two variants at 6q25.1, both of which are known breast cancer susceptibility loci: rs9485370 in the TAB2 gene (P = 4.8 × 10−9 for percent MD and P = 2.5 × 10−8 for absolute MD) and rs60705924 in the CCDC170/ESR1 region (P = 2.2 × 10−8 for absolute MD). Both regions have been implicated in estrogen receptor signaling with TAB2 being a potential regulator of tamoxifen response.ConclusionsWe identified two novel MD loci at 6q25.1. These findings underscore the importance of 6q25.1 as a susceptibility region and provide more insight into the mechanisms through which MD influences breast cancer risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0591-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Identification of two novel mammographic density loci at 6Q25.1

Brand

Humphreys

et al. 2015

Breast Cancer Res

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“…4,5,15 The high risk of breast cancer from breast density has been linked to high epithelial and stromal cells and collagen concentrations in the microenvironment of dense breasts 8,36 and increased activity of mitogens and mutagens in dense breast tissue. 37,38 Breast cancers evolve from epithelial cells; stromal cells stimulate epithelial cells' proliferation through insulin-like growth factor 1 (IGF-1) and transforming growth factor beta, 39 and collagen in the breast microenvironment assists in tumour reorganization. 40 Therefore, increased concentration of each of these components increases the risk of carcinogenesis.…”

Section: Breast Density and Breast Cancer Riskmentioning

confidence: 99%

Measurement of breast density with digital breast tomosynthesis—a systematic review

Ekpo¹,

McEntee²

2014

BJR

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Digital breast tomosynthesis (DBT) has gained acceptance as an adjunct to digital mammography in screening. Now that breast density reporting is mandated in several states in the USA, it is increasingly important that the methods of breast density measurement be robust, reliable and consistent. Breast density assessment with DBT needs some consideration since quantitative methods are modelled for two-dimensional (2D) mammography. A review of methods used for breast density assessment with DBT was performed. Existing evidence shows Cumulus has better reproducibility than that of the breast imaging reporting and data system (BI-RADS®) but still suffers from subjective variability; MedDensity is limited by image noise, whilst Volpara and Quantra are robust and consistent. The reported BI-RADs inter-reader breast density agreement (k) ranged from 0.65 to 0.91, with inter-reader correlation (r) ranging from 0.70 to 0.93. The correlation (r) between BI-RADS and Cumulus ranged from 0.54-0.94, whilst that of BI-RADs and MedDensity ranged from 0.48-0.78. The reported agreement (k) between BI-RADs and Volpara is 0.953. Breast density correlation between DBT and 2D mammography ranged from 0.73 to 0.97, with agreement (k) ranging from 0.56 to 0.96. To avoid variability and provide more reliable breast density information for clinicians, automated volumetric methods are preferred.Breast cancer accounts for approximately 23% of all cancers in females and is the most frequent cause of cancer deaths in females worldwide.

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“…The third variant, rs4803455 was not significantly associated in this study with the minor allele conferred protective effect based on OR=0.61. The data was contradicted to Lee et al (2013) in which the variant showed a fairly association with p value of 0.034 among Singapore Chinese women and the association was observed among nulliparous women. The contradictory might be due to ethnicity factor in which the women in this study was majority among 98% Malays.…”

Section: Discussionmentioning

confidence: 70%

“…Overall, SNPs give MAF of 0.35 with OR of 3 require 50 samples for each case and control sample sets project a power of 97% (Johnson et al 2001). This priori power calculation was based on the data generated by Hap Map database and Lee et al (2013) in Singapore Chinese women.…”

Section: Subjects Recruitmentmentioning

confidence: 99%