Displaying publications 81 - 100 of 180 in total

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  1. Bhoo-Pathy N, Verkooijen HM, Taib NA, Hartman M, Yip CH
    Br J Surg, 2011 Nov;98(11):1566-72.
    PMID: 21858791 DOI: 10.1002/bjs.7650
    Advanced breast cancer is common in less affluent parts of Asia. The impact of breast surgery on survival of women presenting with metastatic breast cancer in this setting was investigated.
  2. Bhoo-Pathy NT, Inaida S, Tanaka S, Taib NA, Yip CH, Saad M, et al.
    Cancer Epidemiol, 2017 06;48:56-61.
    PMID: 28371729 DOI: 10.1016/j.canep.2017.03.007
    BACKGROUND: The benefit of adjuvant chemotherapy in women with T1N0M0 breast cancers is unclear. While gene expression-based prognostic assays may aid management of women with early estrogen receptor (ER) positive tumors, therapeutic decision-making in women with early stage ER negative tumors remains fraught with difficulties. We investigated the association between adjuvant chemotherapy and overall survival in women with T1N0M0, hormone receptor negative breast cancers.

    METHOD: All newly diagnosed breast cancer patients with node-negative and hormone receptor negative tumors measuring≤2cm at the University Malaya Medical Centre (Malaysia) from 1993 to 2013 were included. Mortality of patients with and without adjuvant chemotherapy were compared and adjusted for possible confounders using propensity score.

    RESULTS: Of 6732 breast cancer patients, 341 (5.1%) had small (≤2cm), node-negative and hormone receptor negative tumors at diagnosis. Among them, only 214 (62.8%) received adjuvant chemotherapy. Five-year overall survival was 88.1% (95% confidence interval (CI): 82.0%-94.2%) for patients receiving chemotherapy and 89.6% (95% CI: 85.1%-94.1%) for patients without chemotherapy. Chemotherapy was not associated with survival following adjustment for age, ethnicity, tumor size, tumor grade, HER2 status, lympho-vascular invasion, type of surgery and radiotherapy administration. However, chemotherapy was associated with a significant survival advantage (adjusted hazard ratio: 0.35, 95%CI: 0.14-0.91) in a subgroup of women with high-grade tumors.

    CONCLUSION: Adjuvant chemotherapy does not appear to be associated with a survival benefit in women with T1N0M0, hormone receptor negative breast cancer except in those with high-grade tumors.

  3. Balakrishnan N, Teo SH, Sinnadurai S, Bhoo Pathy NT, See MH, Taib NA, et al.
    World J Surg, 2017 11;41(11):2735-2745.
    PMID: 28653143 DOI: 10.1007/s00268-017-4081-9
    BACKGROUND: Reproductive factors are associated with risk of breast cancer, but the association with breast cancer survival is less well known. Previous studies have reported conflicting results on the association between time since last childbirth and breast cancer survival. We determined the association between time since last childbirth (LCB) and survival of women with premenopausal and postmenopausal breast cancers in Malaysia.

    METHOD: A historical cohort of 986 premenopausal, and 1123 postmenopausal, parous breast cancer patients diagnosed from 2001 to 2012 in University Malaya Medical Centre were included in the analyses. Time since LCB was categorized into quintiles. Multivariable Cox regression was used to determine whether time since LCB was associated with survival following breast cancer, adjusting for demographic, tumor, and treatment characteristics.

    RESULTS: Premenopausal breast cancer patients with the most recent childbirth (LCB quintile 1) were younger, more likely to present with unfavorable prognostic profiles and had the lowest 5-year overall survival (OS) (66.9; 95% CI 60.2-73.6%), compared to women with longer duration since LCB (quintile 2 thru 5). In univariable analysis, time since LCB was inversely associated with risk of mortality and the hazard ratio for LCB quintile 2, 3, 4, and 5 versus quintile 1 were 0.53 (95% CI 0.36-0.77), 0.49 (95% CI 0.33-0.75), 0.61 (95% CI 0.43-0.85), and 0.64 (95% CI 0.44-0.93), respectively; P trend = 0.016. However, this association was attenuated substantially following adjustment for age at diagnosis and other prognostic factors. Similarly, postmenopausal breast cancer patients with the most recent childbirth were also more likely to present with unfavorable disease profiles. Compared to postmenopausal breast cancer patients in LCB quintile 1, patients in quintile 5 had a higher risk of mortality. This association was not significant following multivariable adjustment.

    CONCLUSION: Time since LCB is not independently associated with survival in premenopausal or postmenopausal breast cancers. The apparent increase in risks of mortality in premenopausal breast cancer patients with a recent childbirth, and postmenopausal patients with longer duration since LCB, appear to be largely explained by their age at diagnosis.

  4. Ng PS, Wen WX, Fadlullah MZ, Yoon SY, Lee SY, Thong MK, et al.
    Clin Genet, 2016 10;90(4):315-23.
    PMID: 26757417 DOI: 10.1111/cge.12735
    Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.
  5. Hasmad HN, Sivanandan K, Lee V, Yip CH, Mohd Taib NA, Teo SH
    Clin Genet, 2015 Apr;87(4):392-4.
    PMID: 25066186 DOI: 10.1111/cge.12451
  6. Choong LP, Taib NA, Rampal S, Saad M, Bustam AZ, Yip CH
    Asian Pac J Cancer Prev, 2010;11(5):1409-16.
    PMID: 21198302
    BACKGROUND: Locoregional recurrence after mastectomy for breast cancer may predict distant recurrence and mortality. This study examined the pattern and rates of post-mastectomy locoregional recurrence (PMLRR), survival outcome and prognostic factors for isolated PMLRR (ILR) in a breast cancer cohort in University of Malaya Medical Center (UMMC).

    METHODS: We studied 522 patients who underwent mastectomy between 1998 and 2002 and followed them up until 2008. We defined PMLRR as recurrence to the axilla, supraclavicular nodes and or chest wall. ILR was defined as PMLRR occurring as an isolated event. Prognostic factors for locoregional recurrence were determined using the Cox proportional hazards regression model.

    RESULTS: The overall PMLRR rate was 16.4%. ILR developed in 42 of 522 patients (8.0%). Within this subgroup, 25 (59.5%) remained disease free after treatment while 17 (40.5%) suffered disease progression. Univariate analyses identified race, age, size, stage, margin involvement, lymph node involvement, grade, lymphovascular invasion and ER status as probable prognostic factors for ILR. Cox regression resulted in only stage III disease and margin involvement as independent prognostic factors. The hazard of ILR was 2.5 times higher when the margins were involved compared to when they were clear (aHRR 2.5; 95% CI 1.3 to 5.0). Similarly, compared with stage I those with Stage II (aHRR 2.1; 95%CI 0.6 to 6.8) and stage III (aHRR 4.6; 95%CI 1.4 to 15.9) had worse prognosis for ILR.

    CONCLUSION: Margin involvement and stage III disease were identified to be independent prognostic factors for ILR. Close follow-up of high risk patients and prompt treatment of locoregional recurrence were recommended.

  7. Subramaniam S, Kong YC, Chinna K, Kimman M, Ho YZ, Saat N, et al.
    Psychooncology, 2018 09;27(9):2172-2179.
    PMID: 29856903 DOI: 10.1002/pon.4787
    OBJECTIVES: Quality of life and psychological well-being are important patient-centered outcomes, which are useful in evaluation of cancer care delivery. However, evidence from low-income and middle-income countries remains scarce. We assessed health-related quality of life (HRQoL) and prevalence of psychological distress (anxiety or depression), as well as their predictors, among cancer survivors in a middle-income setting.

    METHODS: Through the Association of Southeast Asian Nations Costs in Oncology study, 1490 newly diagnosed cancer patients were followed-up in Malaysia for 1 year. Health-related quality of life was assessed by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EuroQol-5 (EQ-5D) dimension questionnaires at baseline, 3 and 12 months. Psychological distress was assessed by using Hospital Anxiety and Depression Scale. Data were modeled by using general linear and logistic regressions analyses.

    RESULTS: One year after diagnosis, the mean EORTC QLQ-C30 Global Health score of the cancer survivors remained low at 53.0 over 100 (SD 21.4). Fifty-four percent of survivors reported at least moderate levels of anxiety, while 27% had at least moderate levels of depression. Late stage at diagnosis was the strongest predictor of low HRQoL. Increasing age, being married, high-income status, hospital type, presence of comorbidities, and chemotherapy administration were also associated with worse HRQoL. The significant predictors of psychological distress were cancer stage and hospital type.

    CONCLUSION: Cancer survivors in this middle-income setting have persistently impaired HRQoL and high levels of psychological distress. Development of a holistic cancer survivorship program addressing wider aspects of well-being is urgently needed in our settings.

  8. Taib N, Yip Ch, Ranganathan S, Moosa F, Mun K
    Biomed Imaging Interv J, 2006 Jul;2(3):e30.
    PMID: 21614243 MyJurnal DOI: 10.2349/biij.2.3.e30
    Angiosarcoma of the breast is an extremely rare condition. This case illustrates the use of embolisation as a modality of treatment for primary breast angiosarcoma. No other case has been reported on the use of embolisation for this disorder.
  9. Bhoo Pathy N, Uiterwaal CS, Taib NA, Verkooijen HM, Yip CH
    J Clin Epidemiol, 2012 May;65(5):568-71.
    PMID: 22269329 DOI: 10.1016/j.jclinepi.2011.09.013
    Many recent studies investigated the prognostic value of new biomarkers in breast cancer using data from cancer registries. Some of these studies were conducted using only patients for whom biomarker status was available (or tested). Using human epidermal growth factor receptor 2 (HER2) as an example, we determined whether testing for a recently introduced biomarker was associated with the outcome of women with breast cancer.
  10. Naidu R, Har YC, Taib NA
    Pathol. Int., 2010 Sep;60(9):614-20.
    PMID: 20712647 DOI: 10.1111/j.1440-1827.2010.02568.x
    The aim of the present study was to evaluate the association between the Glyoxalase I (GLOI) Ala111Glu polymorphism and breast cancer risk among the major Malaysian ethnic groups, the Malays, Chinese and Indians, as well as clinico-pathological characteristics of these patients. Genotyping of GLOI gene was performed on blood samples obtained from 387 patients and 252 normal healthy women who had no history of any malignancy using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype and allele frequencies of GLOI polymorphism were not significantly different between the patients and normal individuals among the Malays (P= 0.721, 0.402), Chinese (P= 0.208, 0.079) and Indians (P= 0.612, 0.349), respectively. The Malay, Chinese and Indian women who were Glu/Glu homozygotes (P= 0.419, 0.093, 0.367), Ala/Glu heterozygotes (P= 0.648, 0.182, 0.402) and carriers of Glu allele (P= 0.402, 0.079, 0.349), respectively, were not associated with breast cancer risk. The Glu allele genotype was significantly associated with absence of progesterone receptor (P= 0.036). Thus, the polymorphic variant of the GLOI gene might not be a useful genetic marker to identify Malaysian Malay, Chinese or Indian women who could be at greater risk of developing breast cancer.

    Study site: Universiti Malaya Medical Centre (UMMC)
  11. Yip CH, Evans DG, Agarwal G, Buccimazza I, Kwong A, Morant R, et al.
    World J Surg, 2019 05;43(5):1264-1270.
    PMID: 30610270 DOI: 10.1007/s00268-018-04897-6
    Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5-10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90-95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.
  12. Ho PJ, Khng AJ, Loh HW, Ho WK, Yip CH, Mohd-Taib NA, et al.
    Genome Med, 2021 Dec 02;13(1):185.
    PMID: 34857041 DOI: 10.1186/s13073-021-00978-9
    BACKGROUND: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent.

    METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease.

    RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]).

    CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

  13. 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 

  14. Michailidou K, Beesley J, Lindstrom S, Canisius S, Dennis J, Lush MJ, et al.
    Nat Genet, 2015 Apr;47(4):373-80.
    PMID: 25751625 DOI: 10.1038/ng.3242
    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.
  15. Naidu R, Yip CH, Taib NA
    Med Oncol, 2012 Jun;29(2):411-7.
    PMID: 21301999 DOI: 10.1007/s12032-011-9837-8
    The purpose of the present study was to evaluate the association between TCF7L2 rs12255372(G/T) or rs7903146(C/T) polymorphism and breast cancer risk, and clinico-pathologic characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. The allele (P = 0.033) frequency of rs7903146 (T) polymorphism was significantly higher in the cancer patients than normal individuals. No significant association was demonstrated between CT (OR(adj) = 1.386; 95% CI, 0.985-1.949) or TT (OR(adj) = 1.579; 95% CI, 0.869-2.870) genotype and breast cancer risk. However, women who were carriers of T allele (OR(adj) = 1.316; 95% CI, 1.022-1.695) or T allele genotype (OR(adj) = 1.419; 95% CI, 1.027-1.960) showed significant increased risk of breast cancer. Women who were GT heterozygotes (OR(adj) = 1.329; 95% CI, 0.948-1.862) or TT homozygotes (OR(adj) = 1.574; 95% CI, 0.829-2.987), and carriers of T allele genotype (OR(adj) = 1.365; 95% CI, 0.989-1.883) or T allele (OR(adj) = 1.284; 95% CI, 0.995-1.657) were not associated with breast cancer risk. The rs7903146(T) allele genotype was significantly associated with nodal involvement (P = 0.003) but rs12255372 (T) allele genotype was not associated with the clinico-pathologic characteristics. In conclusion, our findings suggest that rs7903146 (T) variant may elevate the risk of breast cancer, thus could be a potential candidate for breast cancer susceptibility. The variant may also increase the metastatic potential of the tumor.
  16. Naidu R, Har YC, Taib NA
    APMIS, 2011 Jul;119(7):460-7.
    PMID: 21635553 DOI: 10.1111/j.1600-0463.2011.02753.x
    In the present study, we evaluated the association between the TP53BP1 Glu353Asp and T-885G polymorphisms and breast cancer risk as well as with the clinicopathological characteristics of the patients. Genotyping of these polymorphisms was performed on 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy using PCR-RFLP method in a hospital-based Malaysian population. Breast cancer risk was not observed among women who were heterozygous (OR(adj) = 0.887; 95% CI, 0.632-1.245) or homozygous (OR(adj) = 1.083; 95% CI, 0.595-1.969) for Asp allele, and those carriers of Asp allele (OR(adj) = 0.979; 95% CI, 0.771-1.243). Similarly, women who were TG heterozygotes (OR(adj) = 1.181; 95% CI, 0.842-1.658) or GG homozygotes (OR(adj) = 1.362; 95% CI, 0.746-2.486) and carriers of G allele (OR(adj) = 1.147; 95% CI, 0.903-1.458) were not associated with increased risk of breast cancer. Asp allele genotype was significantly associated with ER negativity (p = 0.0015) and poorly differentiated tumours (p = 0.008), but G allele genotype was not associated with the clinicopathological characteristics. In conclusion, Glu353Asp and T-885G polymorphic variants might not have an influence on breast cancer risk, thus might not be potential candidates for cancer susceptibility. Glu353Asp variant might be associated with tumour aggressiveness as defined by its association with ER negativity and poorly differentiated tumours.
  17. Yoon SY, Thong MK, Taib NA, Yip CH, Teo SH
    Fam Cancer, 2011 Jun;10(2):199-205.
    PMID: 21318382 DOI: 10.1007/s10689-011-9420-7
    Genetic counseling (GC) and genetic testing are vital risk management strategies in hereditary breast and ovarian cancer (HBOC) syndromes. Hitherto, cancer genetic testing amongst Asians has been described only in developed and high-income Asian countries. We studied the uptake and acceptance of GC and genetic testing services to Asian BRCA carriers in a middle-income country. A total of 363 patients were tested by full sequencing and large rearrangement analysis of both BRCA1 and BRCA2 genes in the Malaysian Breast Cancer (MyBrCa) Genetic Study. Of these, 49 index patients (13.5%) were found to carry deleterious mutations. GC pre- and post- result disclosures were provided and these groups of patients and their families were studied. GC and genetic testing were accepted by 82% of Malaysian patients at high risk for HBOC syndromes. However, risk assessment was limited by large, geographically dispersed, often polygamous or polyandrous families, and the lack of complete cancer registry. Cultural taboos about cancer diagnoses, social marginalization and lack of regulatory control of genetic discrimination were significant concerns. Only 78% of index patients informed their families of their risks and 11% of relatives came forward when offered free counseling and testing. Even when GC and genetic testing are provided at no cost, there remain significant societal and regulatory barriers to effective cancer genetic services in this underserved Asian population. Families believe there is a need for regulatory protection against genetic discrimination. Further studies are needed in the area of increasing awareness about the potential benefits of GC and genetic testing in Asians.
  18. Park J, Choi JY, Choi J, Chung S, Song N, Park SK, et al.
    Cancers (Basel), 2021 May 14;13(10).
    PMID: 34069208 DOI: 10.3390/cancers13102370
    In this study we aim to examine gene-environment interactions (GxEs) between genes involved with estrogen metabolism and environmental factors related to estrogen exposure. GxE analyses were conducted with 1970 Korean breast cancer cases and 2052 controls in the case-control study, the Seoul Breast Cancer Study (SEBCS). A total of 11,555 SNPs from the 137 candidate genes were included in the GxE analyses with eight established environmental factors. A replication test was conducted by using an independent population from the Breast Cancer Association Consortium (BCAC), with 62,485 Europeans and 9047 Asians. The GxE tests were performed by using two-step methods in GxEScan software. Two interactions were found in the SEBCS. The first interaction was shown between rs13035764 of NCOA1 and age at menarche in the GE|2df model (p-2df = 1.2 × 10-3). The age at menarche before 14 years old was associated with the high risk of breast cancer, and the risk was higher when subjects had homozygous minor allele G. The second GxE was shown between rs851998 near ESR1 and height in the GE|2df model (p-2df = 1.1 × 10-4). Height taller than 160 cm was associated with a high risk of breast cancer, and the risk increased when the minor allele was added. The findings were not replicated in the BCAC. These results would suggest specificity in Koreans for breast cancer risk.
  19. Baxter JS, Johnson N, Tomczyk K, Gillespie A, Maguire S, Brough R, et al.
    Am J Hum Genet, 2021 Jul 01;108(7):1190-1203.
    PMID: 34146516 DOI: 10.1016/j.ajhg.2021.05.013
    A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3. We identified putative regulatory elements that enhanced cell-type-specific transcription from the IGFBP5 promoter at both signals (30- to 40-fold increased expression by the putative regulatory element at signal 2, 2- to 3-fold by the putative regulatory element at signal 3). We further identified one of the five credible causal variants at signal 2, a 1.4 kb deletion (esv3594306), as the likely causal variant; the deletion allele of this variant was associated with an average additional increase in IGFBP5 expression of 1.3-fold (MCF-7) and 2.2-fold (T-47D). We propose a model in which the deletion allele of esv3594306 juxtaposes two transcription factor binding regions (annotated by estrogen receptor alpha ChIP-seq peaks) to generate a single extended regulatory element. This regulatory element increases cell-type-specific expression of the tumor suppressor gene IGFBP5 and, thereby, reduces risk of estrogen receptor-positive breast cancer (odds ratio = 0.77, 95% CI 0.74-0.81, p = 3.1 × 10-31).
  20. Mollica MA, Mayer DK, Oeffinger KC, Kim Y, Buckenmaier SS, Sivaram S, et al.
    JCO Glob Oncol, 2020 09;6:1394-1411.
    PMID: 32955943 DOI: 10.1200/GO.20.00180
    PURPOSE: The purpose of this study was to describe follow-up care for breast and colorectal cancer survivors in countries with varying levels of resources and highlight challenges regarding posttreatment survivorship care.

    METHODS: We surveyed one key stakeholder from each of 27 countries with expertise in survivorship care on questions including the components/structure of follow-up care, delivery of treatment summaries and survivorship care plans, and involvement of primary care in survivorship. Descriptive analyses were performed to characterize results across countries and variations between the WHO income categories (low, middle, high). We also performed a qualitative content analysis of narratives related to survivorship care challenges to identify major themes.

    RESULTS: Seven low- or /lower-middle-income countries (LIC/LMIC), seven upper-middle-income countries (UMIC), and 13 high-income countries (HICs) were included in this study. Results indicate that 44.4% of countries with a National Cancer Control Plan currently address survivorship care. Additional findings indicate that HICs use guidelines more often than those in LICs/LMICs and UMICs. There was great variation among countries regardless of income level. Common challenges include issues with workforce, communication and care coordination, distance/transportation issues, psychosocial support, and lack of focus on follow-up care.

    CONCLUSION: This information can guide researchers, providers, and policy makers in efforts to improve the quality of survivorship care on a national and global basis. As the number of cancer survivors increases globally, countries will need to prioritize their long-term needs. Future efforts should focus on efforts to bridge oncology and primary care, building international partnerships, and implementation of guidelines.

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