Displaying publications 1 - 20 of 29 in total

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  1. Hassan N, Ho WK, Mariapun S, Teo SH
    BMC Public Health, 2015;15:548.
    PMID: 26065413 DOI: 10.1186/s12889-015-1892-1
    To date, because of limited budgets and lower incidence of breast cancer, the majority of Asian countries do not have population-based screening programmes, but instead offer opportunistic screening. However, there have been few studies which have assessed the motivators for women attending such programmes and the appropriateness of the programmes in terms of targeting women at risk.
  2. Lee M, Mariapun S, Rajaram N, Teo SH, Yip CH
    BMC Public Health, 2017 01 28;17(1):127.
    PMID: 28129762 DOI: 10.1186/s12889-017-4015-3
    BACKGROUND: The incidence of breast cancer in Asia is increasing because of urbanization and lifestyle changes. In the developing countries in Asia, women present at late stages, and mortality is high. Mammographic screening is the only evidence-based screening modality that reduces breast cancer mortality. To date, only opportunistic screening is offered in the majority of Asian countries because of the lack of justification and funding. Nevertheless, there have been few reports on the effectiveness of such programmes. In this study, we describe the cancer detection rate and challenges experienced in an opportunistic mammographic screening programme in Malaysia.

    METHODS: From October 2011 to June 2015, 1,778 asymptomatic women, aged 40-74 years, underwent subsidised mammographic screening. All patients had a clinical breast examination before mammographic screening, and women with mammographic abnormalities were referred to a surgeon. The cancer detection rate and variables associated with a recommendation for adjunct ultrasonography were determined.

    RESULTS: The mean age for screening was 50.8 years and seven cancers (0.39%) were detected. The detection rate was 0.64% in women aged 50 years and above, and 0.12% in women below 50 years old. Adjunct ultrasonography was recommended in 30.7% of women, and was significantly associated with age, menopausal status, mammographic density and radiologist's experience. The main reasons cited for recommendation of an adjunct ultrasound was dense breasts and mammographic abnormalities.

    DISCUSSION: The cancer detection rate is similar to population-based screening mammography programmes in high-income Asian countries. Unlike population-based screening programmes in Caucasian populations where the adjunct ultrasonography rate is 2-4%, we report that 3 out of 10 women attending screening mammography were recommended for adjunct ultrasonography. This could be because Asian women attending screening are likely premenopausal and hence have denser breasts. Radiologists who reported more than 360 mammograms were more confident in reporting a mammogram as normal without adjunct ultrasonography compared to those who reported less than 180 mammograms.

    CONCLUSION: Our subsidised opportunistic mammographic screening programme is able to provide equivalent cancer detection rates but the high recall for adjunct ultrasonography would make screening less cost-effective.

  3. Mariapun S, Ho WK, Kang PC, Li J, Lindström S, Yip CH, et al.
    Cancer Epidemiol Biomarkers Prev, 2016 Feb;25(2):327-33.
    PMID: 26677210 DOI: 10.1158/1055-9965.EPI-15-0746
    Mammographic density is an established risk factor for breast cancer and has a strong heritable component. Genome-wide association studies (GWAS) for mammographic density conducted in women of European descent have identified several genetic associations, but none of the studies have been tested in Asians. We sought to investigate whether these genetic loci, and loci associated with breast cancer risk and breast size, are associated with mammographic density in an Asian cohort.
  4. Mariapun S, Li J, Yip CH, Taib NA, Teo SH
    PLoS One, 2015;10(2):e0117568.
    PMID: 25659139 DOI: 10.1371/journal.pone.0117568
    BACKGROUND: Mammographic density is a strong risk factor for breast cancer and is highly variable, but, to date, few studies have examined density in Asian women, particularly those in low and middle-income Asian countries where genetic and lifestyle determinants may be significantly different.
    METHODS: A total of 1,240 women who attended an opportunistic mammogram screening programme were eligible for analysis. Mammographic density was estimated using a fully-automated thresholding method and differences across ethnic groups were examined using linear regression in 205 randomly selected Chinese women, 138 Malay and 199 Indian women.
    RESULTS: Percent density was significantly higher in Chinese women (28.5%; 95% CI 27.0%, 30.0%) compared to Malay (24.2%; 95% CI 22.5%, 26.0%) and Indian (24.3%; 95% CI 22.8%, 25.7%) women (p<0.001), after adjustment for age, BMI, menopausal status, parity and age at first full term pregnancy. Correspondingly, adjusted nondense area was significantly lower in Chinese (72.2cm2; 95% CI 67.9cm2, 76.5cm2) women compared to Malay (92.1cm2; 95% CI 86.9cm2, 97.2cm2) and Indian (97.7cm2; 95% CI 93.4cm2, 101.9cm2) women (p<0.001), but dense area did not differ across the three ethnic groups.
    CONCLUSIONS: Our study shows that higher percent density and lower nondense area reflect the higher incidence of breast cancer in Chinese compared to Malay and Indian women in Malaysia. Known lifestyle determinants of mammographic density do not fully account for the ethnic variations observed in mammographic density in this Asian cohort.
  5. Tan M, Mariapun S, Yip CH, Ng KH, Teo SH
    Phys Med Biol, 2019 01 31;64(3):035016.
    PMID: 30577031 DOI: 10.1088/1361-6560/aafabd
    Historically, breast cancer risk prediction models are based on mammographic density measures, which are dichotomous in nature and generally categorize each voxel or area of the breast parenchyma as 'dense' or 'not dense'. Using these conventional methods, the structural patterns or textural components of the breast tissue elements are not considered or ignored entirely. This study presents a novel method to predict breast cancer risk that combines new texture and mammographic density based image features. We performed a comprehensive study of the correlation of 944 new and conventional texture and mammographic density features with breast cancer risk on a cohort of Asian women. We studied 250 breast cancer cases and 250 controls matched at full-field digital mammography (FFDM) status for age, BMI and ethnicity. Stepwise regression analysis identified relevant features to be included in a linear discriminant analysis (LDA) classifier model, trained and tested using a leave-one-out based cross-validation method. The area under the receiver operating characteristic (AUC) and adjusted odds ratios (ORs) were used as the two performance assessment indices in our study. For the LDA trained classifier, the adjusted OR was 6.15 (95% confidence interval: 3.55-10.64) and for Volpara volumetric breast density, 1.10 (0.67-1.81). The AUC for the LDA trained classifier was 0.68 (0.64-0.73), compared to 0.52 (0.47-0.57) for Volpara volumetric breast density (p   
  6. Soh WH, Rajaram N, Mariapun S, Eriksson M, Fadzli F, Ho WK, et al.
    Cancer Causes Control, 2018 Sep;29(9):883-894.
    PMID: 30062608 DOI: 10.1007/s10552-018-1064-6
    BACKGROUND: Physical activity is a modifiable lifestyle factor associated with reduced breast cancer risk. Mammographic density is a strong, independent risk factor for breast cancer, and some breast cancer risk factors have been shown to modify mammographic density. However, the effect of physical activity on mammographic density, studied predominantly among Caucasians, has yielded conflicting results. In this study, we examined, in an Asian population, the association between physical activity and mammographic density.

    METHODS: We conducted a cross-sectional study of 2,377 Malaysian women aged 40-74 years. Physical activity information was obtained at screening mammogram and mammographic density was measured from mammograms by the area-based STRATUS method (n = 1,522) and the volumetric Volpara™ (n = 1,200) method. Linear regression analyses were performed to evaluate the association between physical activity and mammographic density, adjusting for potential confounders.

    RESULTS: We observed that recent physical activity was associated with area-based mammographic density measures among postmenopausal women, but not premenopausal women. In the fully adjusted model, postmenopausal women with the highest level of recent physical activity had 8.0 cm2 [95% confidence interval: 1.3, 14.3 cm2] lower non-dense area and 3.1% [0.1, 6.3%] higher area-based percent density, compared to women with the lowest level of recent physical activity. Physical activity was not associated to volumetric mammographic density.

    CONCLUSIONS: Our findings suggest that the beneficial effects of physical activity on breast cancer risk may not be measurable through mammographic density. Future research is needed to identify appropriate biomarkers to assess the effect of physical activity on breast cancer risk.

  7. Lai KN, Ho WK, Kang IN, Kang PC, Phuah SY, Mariapun S, et al.
    BMC Cancer, 2017 02 22;17(1):149.
    PMID: 28222693 DOI: 10.1186/s12885-017-3099-6
    BACKGROUND: Genetic testing for BRCA1 and BRCA2 has led to the accurate identification of individuals at higher risk of cancer and the development of new therapies. Approximately 10-20% of the genetic testing for BRCA1 and BRCA2 leads to the identification of variants of uncertain significance (VUS), with higher proportions in Asians. We investigated the functional significance of 7 BRCA1 and 25 BRCA2 variants in a multi-ethnic Asian cohort using a case-control approach.

    METHODS: The MassARRAY genotyping was conducted in 1,394 Chinese, 406 Malay and 310 Indian breast cancer cases and 1,071 Chinese, 167 Malay and 255 Indian healthy controls. The association of individual variant with breast cancer risk was analyzed using logistic regression model adjusted for ethnicity, age and family history.

    RESULTS: Our study confirmed BRCA2 p.Ile3412Val is presented in >2% of unaffected women and is likely benign, and BRCA2 p.Ala1996Thr which is predicted to be likely pathogenic by in-silico models is presented in 2% of healthy Indian women suggesting that it may not be associated with breast cancer risk. Single-variant analysis suggests that BRCA1 p.Arg762Ser may be associated with breast cancer risk (OR = 7.4; 95% CI, 0.9-62.3; p = 0.06).

    CONCLUSIONS: Our study shows that BRCA2 p.Ile3412Val and p.Ala1996Thr are likely benign and highlights the need for population-specific studies to determine the likely functional significance of population-specific variants. Our study also suggests that BRCA1 p.Arg762Ser may be associated with increased risk of breast cancer but other methods or larger studies are required to determine a more precise estimate of breast cancer risk.

  8. Lee DS, Meiser B, Mariapun S, Hassan T, Yip CH, Mohd Taib NA, et al.
    J Genet Couns, 2021 Jun;30(3):720-729.
    PMID: 33245177 DOI: 10.1002/jgc4.1360
    The vast majority of studies assessing communication of BRCA1/2 results with relatives and family uptake of BRCA1/2 testing have been conducted in Western societies, and a dearth of studies have been conducted in Asia among relatives of diverse carriers of pathogenic BRCA1/2 germline variants. This study aimed to present rates of BRCA1/2 result disclosure by probands and probands' motivators and barriers of family communication and predictive testing uptake among eligible relatives. It also examined patterns of disclosure and testing uptake among different types of relatives. Eighty-seven carriers with either breast or ovarian cancer, who had previously been found to be carriers of a pathogenic variant in BRCA1/2, were interviewed over the phone using a semi-structured interview guide. Fifty-six percent of patients were Chinese, 21% were Indian, and 23% were Malay. It was found that 62.0% of eligible first- and second-degree relatives were informed by the proband about the testing result and that 11.5% of eligible first- and second-degree relatives had genetic testing. First-degree relatives were more likely to have been informed and tested compared to second-degree relatives, as were sisters compared to brothers. The low rates of family communication and testing uptake documented in this study suggest that interventions should focus on encouraging probands to inform male and second-degree relatives and targeting such relatives to increase informed decisions and accessibility to testing. Promotion strategies should be culturally sensitive to optimize outcomes.
  9. Wen WX, Soo JS, Kwan PY, Hong E, Khang TF, Mariapun S, et al.
    Breast Cancer Res, 2016 05 27;18(1):56.
    PMID: 27233495 DOI: 10.1186/s13058-016-0717-1
    BACKGROUND: APOBEC3B is a cytosine deaminase implicated in immune response to viral infection, cancer predisposition and carcinogenesis. Germline APOBEC3B deletion is more common in East Asian women and confers a modest risk to breast cancer in both East Asian and Caucasian women. Analysis of tumour samples from women of European descent has shown that germline APOBEC3B deletion is associated with an increased propensity to develop somatic mutations and with an enrichment for immune response-related gene sets. However, this has not been examined in Asian tumour samples, where population differences in genetic and dietary factors may have an impact on the immune system.

    METHODS: In this study, we determined the prevalence of germline APOBEC3B deletion and its association with breast cancer risk in a cross-sectional hospital-based Asian multi-ethnic cohort of 1451 cases and 1442 controls from Malaysia. We compared gene expression profiles of breast cancers arising from APOBEC3B deletion carriers and non-carriers using microarray analyses. Finally, we characterised the overall abundance of tumour-infiltrating immune cells in breast cancers from TCGA and METABRIC using ESTIMATE and relative frequency of 22 immune cell subsets in breast cancers from METABRIC using CIBERSORT.

    RESULTS: The minor allelic frequency of APOBEC3B deletion was estimated to be 0.35, 0.42 and 0.16 in female populations of Chinese, Malay and Indian descent, respectively, and that germline APOBEC3B deletion was associated with breast cancer risk with odds ratios of 1.23 (95 % CI: [1.05, 1.44]) for one-copy deletion and 1.38 (95 % CI: [1.10, 1.74]) for two-copy deletion compared to women with no deletion. Germline APOBEC3B deletion was not associated with any clinicopathologic features or the expression of any APOBEC family members but was associated with immune response-related gene sets (FDR q values 

  10. Rajaram N, Mariapun S, Eriksson M, Tapia J, Kwan PY, Ho WK, et al.
    Breast Cancer Res Treat, 2017 01;161(2):353-362.
    PMID: 27864652 DOI: 10.1007/s10549-016-4054-y
    PURPOSE: Mammographic density is a measurable and modifiable biomarker that is strongly and independently associated with breast cancer risk. Paradoxically, although Asian women have lower risk of breast cancer, studies of minority Asian women in predominantly Caucasian populations have found that Asian women have higher percent density. In this cross-sectional study, we compared the distribution of mammographic density for a matched cohort of Asian women from Malaysia and Caucasian women from Sweden, and determined if variations in mammographic density could be attributed to population differences in breast cancer risk factors.

    METHODS: Volumetric mammographic density was compared for 1501 Malaysian and 4501 Swedish healthy women, matched on age and body mass index. We used multivariable log-linear regression to determine the risk factors associated with mammographic density and mediation analysis to identify factors that account for differences in mammographic density between the two cohorts.

    RESULTS: Compared to Caucasian women, percent density was 2.0% higher among Asian women (p 

  11. Kang P, Mariapun S, Phuah SY, Lim LS, Liu J, Yoon SY, et al.
    Breast Cancer Res Treat, 2010 Nov;124(2):579-84.
    PMID: 20617377 DOI: 10.1007/s10549-010-1018-5
    Early studies of genetic predisposition due to the BRCA1 and BRCA2 genes have focused largely on sequence alterations, but it has now emerged that 4-28% of inherited mutations in the BRCA genes may be due to large genomic rearrangements of these genes. However, to date, there have been relatively few studies of large genomic rearrangements in Asian populations. We have conducted a full sequencing and large genomic rearrangement analysis (using Multiplex Ligation-dependent Probe Amplification, MLPA) of 324 breast cancer patients who were selected from a multi-ethnic hospital-based cohort on the basis of age of onset of breast cancer and/or family history. Three unrelated individuals were found to have large genomic rearrangements: 2 in BRCA1 and 1 in BRCA2, which accounts for 2/24 (8%) of the total mutations detected in BRCA1 and 1/23 (4%) of the mutations in BRCA2 detected in this cohort. Notably, the family history of the individuals with these mutations is largely unremarkable suggesting that family history alone is a poor predictor of mutation status in Asian families. In conclusion, this study in a multi-ethnic (Malay, Chinese, Indian) cohort suggests that large genomic rearrangements are present at a low frequency but should nonetheless be included in the routine testing for BRCA1 and BRCA2.
  12. Yoon SYY, Ahmad Bashah NS, Wong SW, Mariapun S, Padmanabhan H, Hassan T, et al.
    Ann Oncol, 2018 Nov;29 Suppl 9:ix176.
    PMID: 32177935 DOI: 10.1093/annonc/mdy483.004
  13. Padmanabhan H, Mariapun S, Lee SY, Hassan NT, Lee DS, Meiser B, et al.
    J Genet Couns, 2023 Feb;32(1):43-56.
    PMID: 35913122 DOI: 10.1002/jgc4.1619
    Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost-effective cancer control even in low- and middle-income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short- and long-term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1-month and 2-year post-disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2-year post-result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post-result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture-specific genetic counseling strategies.
  14. Mariapun S, Ho WK, Eriksson M, Tai MC, Mohd Taib NA, Yip CH, et al.
    Breast Cancer Res Treat, 2023 Sep;201(2):237-245.
    PMID: 37338730 DOI: 10.1007/s10549-023-06984-2
    PURPOSE: Mammographic density (MD), after accounting for age and body mass index (BMI), is a strong heritable risk factor for breast cancer. Genome-wide association studies (GWAS) have identified 64 SNPs in 55 independent loci associated with MD in women of European ancestry. Their associations with MD in Asian women, however, are largely unknown.

    METHOD: Using linear regression adjusting for age, BMI, and ancestry-informative principal components, we evaluated the associations of previously reported MD-associated SNPs with MD in a multi-ethnic cohort of Asian ancestry. Area and volumetric mammographic densities were determined using STRATUS (N = 2450) and Volpara™ (N = 2257). We also assessed the associations of these SNPs with breast cancer risk in an Asian population of 14,570 cases and 80,870 controls.

    RESULTS: Of the 61 SNPs available in our data, 21 were associated with MD at a nominal threshold of P value  0.05, 29 variants showed consistent directions of association as those previously reported. We found that nine of the 21 MD-associated SNPs in this study were also associated with breast cancer risk in Asian women (P 

  15. Tan MM, Ho WK, Yoon SY, Mariapun S, Hasan SN, Lee DS, et al.
    PLoS One, 2018;13(9):e0203469.
    PMID: 30216346 DOI: 10.1371/journal.pone.0203469
    BACKGROUND: Breast cancer risk factors have been examined extensively in Western setting and more developed Asian cities/countries. However, there are limited data on developing Asian countries. The purpose of this study was to examine breast cancer risk factors and the change of selected risk factors across birth cohorts in Malaysian women.

    METHODS: An unmatched hospital based case-control study was conducted from October 2002 to December 2016 in Selangor, Malaysia. A total of 3,683 cases and 3,980 controls were included in this study. Unconditional logistic regressions, adjusted for potential confounding factors, were conducted. The breast cancer risk factors were compared across four birth cohorts by ethnicity.

    RESULTS: Ever breastfed, longer breastfeeding duration, a higher soymilk and soy product intake, and a higher level of physical activity were associated with lower risk of breast cancer. Chinese had the lowest breastfeeding rate, shortest breastfeeding duration, lowest parity and highest age of first full term pregnancy.

    CONCLUSIONS: Our study shows that breastfeeding, soy intake and physical activity are modifiable risk factors for breast cancer. With the increasing incidence of breast cancer there is an urgent need to educate the women about lifestyle intervention they can take to reduce their breast cancer risk.

  16. Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, et al.
    J Med Genet, 2018 02;55(2):97-103.
    PMID: 28993434 DOI: 10.1136/jmedgenet-2017-104947
    BACKGROUND: Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls.

    METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing.

    RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing.

    CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.

  17. Dench E, Bond-Smith D, Darcey E, Lee G, Aung YK, Chan A, et al.
    BMJ Open, 2019 Dec 31;9(12):e031041.
    PMID: 31892647 DOI: 10.1136/bmjopen-2019-031041
    INTRODUCTION: For women of the same age and body mass index, increased mammographic density is one of the strongest predictors of breast cancer risk. There are multiple methods of measuring mammographic density and other features in a mammogram that could potentially be used in a screening setting to identify and target women at high risk of developing breast cancer. However, it is unclear which measurement method provides the strongest predictor of breast cancer risk.

    METHODS AND ANALYSIS: The measurement challenge has been established as an international resource to offer a common set of anonymised mammogram images for measurement and analysis. To date, full field digital mammogram images and core data from 1650 cases and 1929 controls from five countries have been collated. The measurement challenge is an ongoing collaboration and we are continuing to expand the resource to include additional image sets across different populations (from contributors) and to compare additional measurement methods (by challengers). The intended use of the measurement challenge resource is for refinement and validation of new and existing mammographic measurement methods. The measurement challenge resource provides a standardised dataset of mammographic images and core data that enables investigators to directly compare methods of measuring mammographic density or other mammographic features in case/control sets of both raw and processed images, for the purposes of the comparing their predictions of breast cancer risk.

    ETHICS AND DISSEMINATION: Challengers and contributors are required to enter a Research Collaboration Agreement with the University of Melbourne prior to participation in the measurement challenge. The Challenge database of collated data and images are stored in a secure data repository at the University of Melbourne. Ethics approval for the measurement challenge is held at University of Melbourne (HREC ID 0931343.3).

  18. Cai Q, Zhang B, Sung H, Low SK, Kweon SS, Lu W, et al.
    Nat Genet, 2014 Aug;46(8):886-90.
    PMID: 25038754 DOI: 10.1038/ng.3041
    In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified 3 genetic loci newly associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene; P=8.82×10(-9)), rs10474352 at 5q14.3 (near the ARRDC3 gene; P=1.67×10(-9)) and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene; P=4.25×10(-8)). We replicated these associations in 16,003 cases and 41,335 controls of European ancestry (P=0.030, 0.004 and 0.010, respectively). Data from the ENCODE Project suggest that variants rs4951011 and rs10474352 might be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.
  19. Jia G, Ping J, Shu X, Yang Y, Cai Q, Kweon SS, et al.
    Am J Hum Genet, 2022 Dec 01;109(12):2185-2195.
    PMID: 36356581 DOI: 10.1016/j.ajhg.2022.10.011
    By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome- and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were associated with breast cancer risk at a p 
  20. Burton A, Byrnes G, Stone J, Tamimi RM, Heine J, Vachon C, et al.
    Breast Cancer Res, 2016 12 19;18(1):130.
    PMID: 27993168
    BACKGROUND: Inter-women and intra-women comparisons of mammographic density (MD) are needed in research, clinical and screening applications; however, MD measurements are influenced by mammography modality (screen film/digital) and digital image format (raw/processed). We aimed to examine differences in MD assessed on these image types.

    METHODS: We obtained 1294 pairs of images saved in both raw and processed formats from Hologic and General Electric (GE) direct digital systems and a Fuji computed radiography (CR) system, and 128 screen-film and processed CR-digital pairs from consecutive screening rounds. Four readers performed Cumulus-based MD measurements (n = 3441), with each image pair read by the same reader. Multi-level models of square-root percent MD were fitted, with a random intercept for woman, to estimate processed-raw MD differences.

    RESULTS: Breast area did not differ in processed images compared with that in raw images, but the percent MD was higher, due to a larger dense area (median 28.5 and 25.4 cm2 respectively, mean √dense area difference 0.44 cm (95% CI: 0.36, 0.52)). This difference in √dense area was significant for direct digital systems (Hologic 0.50 cm (95% CI: 0.39, 0.61), GE 0.56 cm (95% CI: 0.42, 0.69)) but not for Fuji CR (0.06 cm (95% CI: -0.10, 0.23)). Additionally, within each system, reader-specific differences varied in magnitude and direction (p 

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