Displaying publications 1 - 20 of 31 in total

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  1. Yoon KH, Kim JS, Park JY, Park SY, Kiat RYD, Kim SG
    Orthop J Sports Med, 2021 Feb;9(2):2325967120985153.
    PMID: 33709007 DOI: 10.1177/2325967120985153
    Background: There is currently no consensus on the optimal placement of the tibial tunnel for remnant-preserving posterior cruciate ligament (PCL) reconstruction.

    Purpose/Hypothesis: The purpose of this study was to compare the clinical and radiologic outcomes of remnant-preserving PCL reconstruction using anatomic versus low tibial tunnels. We hypothesized that the outcomes of low tibial tunnel placement would be superior to those of anatomic tibial tunnel placement at the 2-year follow-up after remnant-preserving PCL reconstruction.

    Study Design: Cohort study; Level of evidence, 3.

    Methods: We retrospectively reviewed the data for patients who underwent remnant-preserving PCL reconstruction between March 2011 and January 2018 with a minimum follow-up of 2 years (N = 63). On the basis of the tibial tunnel position on postoperative computed tomography, the patients were divided into those with anatomic placement (group A; n = 31) and those with low tunnel placement (group L; n = 32). Clinical scores (International Knee Documentation Committee subjective score, Lysholm score, and Tegner activity level), range of motion, complications, and stability test outcomes at follow-up were compared between the 2 groups. Graft signal on 1-year follow-up magnetic resonance imaging scans was compared between 22 patients in group A and 17 patients in group L.

    Results: There were no significant differences between groups regarding clinical scores or incidence of complications, no between-group differences in posterior drawer test results, and no side-to-side difference on Telos stress radiographs (5.2 ± 2.9 mm in group A vs 5.1 ± 2.8 mm in group L; P = .900). Postoperative 1-year follow-up magnetic resonance imaging scans showed excellent graft healing in both groups, with no significant difference between them.

    Conclusion: The clinical and radiologic outcomes and complication rate were comparable between anatomic tunnel placement and low tibial tunnel placement at 2-year follow-up after remnant-preserving PCL reconstruction. The findings of this study suggest that both tibial tunnel positions are clinically feasible for remnant-preserving PCL reconstruction.

  2. Yoon KH, Lee HW, Park SY, Yeak RDK, Kim JS, Park JY
    Am J Sports Med, 2020 08;48(10):2370-2375.
    PMID: 32692971 DOI: 10.1177/0363546520938771
    BACKGROUND: The purpose of this study was to evaluate the clinical score and stability after meniscal allograft transplantation (MAT) after a previous anterior cruciate ligament (ACL) reconstruction.

    HYPOTHESIS: Medial MAT would improve anteroposterior stability, and lateral MAT would improve rotational stability.

    STUDY DESIGN: Cohort study; Level of evidence, 3.

    METHOD: We retrospectively investigated 31 cases of MAT after a previous total or nearly total meniscectomy and ACL reconstruction between November 2008 and June 2017. Cases were divided into medial (16 cases) and lateral (15 cases) MAT groups. The patients were assessed preoperatively and at the 2-year follow-up.

    RESULTS: In the medial MAT group, the International Knee Documentation Committee, Lysholm, Lysholm instability, and Tegner scores improved significantly at the 2-year follow-up, and there were also significant improvements in the anterior drawer, Lachman, and pivot-shift tests. In the lateral MAT group, the Lysholm and Tegner scores improved significantly at the 2-year follow-up, as had the anterior drawer and Lachman tests but not the pivot-shift test. The medial MAT group showed significant improvement in side-to-side difference on Telos stress radiographs, from 6.5 mm (preoperatively) to 3.6 mm (2-year follow-up) (P = .001), while the lateral MAT group showed no significant change. There was no progression of arthritis in either group.

    CONCLUSION: Medial MAT improved not only anteroposterior stability but also rotational stability in the meniscus-deficient ACL-reconstructed knee. Lateral MAT showed improvements in the anterior drawer and Lachman tests but not in the pivot-shift test or side-to-side difference on Telos stress radiographs in meniscus-deficient ACL-reconstructed knees. Instability and pain are indications for MAT in meniscus-deficient ACL-reconstructed knees.

  3. Yoon KH, Kim JS, Park JY, Park SY, Kiat RYD, Kim SG
    Knee Surg Sports Traumatol Arthrosc, 2021 Jun;29(6):1936-1943.
    PMID: 32914218 DOI: 10.1007/s00167-020-06266-0
    PURPOSE: To compare clinical and radiological outcomes and failure rates between anatomical and high femoral tunnels in remnant-preserving single-bundle posterior cruciate ligament (PCL) reconstruction.

    METHODS: 63 patients who underwent remnant-preserving single-bundle PCL reconstruction between 2011 and 2018 with a minimum 2-year follow-up were retrospectively reviewed. Patients were divided into two groups according to the femoral tunnel position: group A (33 patients with anatomical femoral tunnel) and group H (30 patients with high femoral tunnels). The femoral tunnel was positioned at the center (group A) or upper margin (group H) of the remnant anterolateral bundle. The position of the femoral tunnel was evaluated using the grid method on three-dimensional computed tomography. Clinical and radiological outcomes and failure rates were compared between the groups at the 2-year follow-up.

    RESULTS: The position of the femoral tunnel was significantly high in group H than in group A (87.4% ± 4.2% versus 76.1% ± 3.7%, p 

  4. Park S, Park JY, Song Y, How SH, Jung KS, Respiratory Infections Assembly of the APSR
    Respirology, 2019 Jun;24(6):590-597.
    PMID: 30985968 DOI: 10.1111/resp.13558
    In past decades, we have seen several epidemics of respiratory infections from newly emerging viruses, most of which originated in animals. These emerging infections, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and the pandemic influenza A(H1N1) and avian influenza (AI) viruses, have seriously threatened global health and the economy. In particular, MERS-CoV and AI A(H7N9) are still causing infections in several areas, and some clustering of cases of A(H5N1) and A(H7N9) may imply future possible pandemics. Additionally, given the inappropriate use of antibiotics and international travel, the spread of carbapenem-resistant Gram-negative bacteria is also a significant concern. These infections with epidemic or pandemic potential present a persistent threat to public health and a huge burden on healthcare services in the Asia-Pacific region. Therefore, to enable efficient infection prevention and control, more effective international surveillance and collaboration systems, in the context of the 'One Health' approach, are necessary.
  5. Corduff N, Chao YY, Lam SC, Lim J, Lim TS, Lohia K, et al.
    J Clin Aesthet Dermatol, 2020 Apr;13(4):23-34.
    PMID: 33144908
    OBJECTIVE: A group of established aesthetic physicians sought to develop treatment guidelines for assessing Asian face morphologies that reflect accurate and current beauty standards across Asia. DESIGN: Physicians completed surveys, debated, and voted on their clinical strategies and developed an alternative simplified visual tool of assessment (SVAT) that discerns between country variations in genetic and ideal morphotypes. SETTING: Electronic and paper surveys were followed by consensus debates and voting. PARTICIPANTS: Established aesthetic physicians practicing regularly on Asian patients. MEAUSUREMENTS: A clinically applicable SVAT was developed, which considered facial index, mid-face projection, upper and lower face shape, submalar contour, nose length and dorsal height, eye shape and brow shape, proportion of lips-to-lower face and ratio of upper-to-lower lip, and chin shape. RESULTS: For facial shape change, physicians always assessed the horizontal thirds, facial symmetry, and lip-chin complex profile, and also analyzed overall face shapes and Ogee curves. Criteria for creating oval-shaped faces was also defined and included treating indications, such as loss of angularity and bilateral masseter muscle hypertrophy, narrow jawlines, and longer and wider foreheads. Critical differences and similarities in country-specific aesthetic preferences, treatment requests, and considerations or strategies were uncovered, including the inadequacy of assessing overall peripheral facial shapes. CONCLUSION: This consensus establishes the assessment and treatment criteria for achieving ideal shapes for Asian patients. Specific descriptors are affected by variations; therefore, we present the visual criteria for Asian facial morphotypes. We hope that physicians new to treating Asian patients can use this clinical information to improve their practice.
  6. Goldie K, Kerscher M, Fabi SG, Hirano C, Landau M, Lim TS, et al.
    PMID: 34163203 DOI: 10.2147/CCID.S309374
    Introduction: Skin quality is an important component of human attractiveness. To date, there are no standardized criteria for good skin quality. To establish a consensus for good skin quality parameters and measurement and treatment options, a virtual skin quality advisory board consisting of a global panel of highly experienced aesthetic dermatologists/aesthetic physicians was convened.

    Methods: A total of 10 dermatologists/aesthetic physicians served on the advisory board. A modified version of the Delphi method was used to arrive at consensus. Members accessed an online platform to review statements on skin quality criteria from their peers, including treatment and measurement options, and voted to indicate whether they agreed or disagreed. Statements that did not have agreement were modified and the members voted again. Consensus was defined as: strong consensus = greater than 95% agreement; consensus = 75% to 95% agreement; majority consent = 50% to 75% agreement; no consensus = less than 50% agreement.

    Results: There was strong consensus that good skin quality is defined as healthy, youthful in appearance (appearing younger than a person's chronological age), undamaged skin and that skin quality can be described across all ethnicities by four emergent perceptual categories (EPCs): skin tone evenness, skin surface evenness, skin firmness, and skin glow. The EPCs can be affected by multiple tissue layers (ie, skin surface quality can stem from and be impacted by deep structures or tissues). This means that topical approaches may not be sufficient. Instead, improving skin quality EPCs can require a multilayer treatment strategy.

    Conclusion: This global advisory board established strong consensus that skin quality can be described by four EPCs, which can help clinicians determine the appropriate treatment option(s) and the tissue or skin layer(s) to address. Skin quality is important to human health and wellbeing and patients' perception for the need for aesthetic treatment.

  7. Park JY, Lin F, Suwanchinda A, Wanitphakdeedecha R, Yu J, Lim TS, et al.
    J Clin Aesthet Dermatol, 2021 May;14(5):E70-E79.
    PMID: 34188753
    BACKGROUND: Noninvasive facial-rejuvenation devices, such as nonablative radiofrequency (RF) and laser-assisted technology, are increasingly replacing higher-risk surgeries for face and body skin laxity. OBJECTIVE: We sought to review published information on noninvasive energy device safety and efficacy in aesthetic skin tightening, compare these with our experiences in Asian patients, and disseminate a consensus for optimizing microfocused ultrasound with visualization (MFU-V) in Asian patients. METHODS: A broad, nonexhaustive, nonsystematic literature search of published studies indexed in PubMed was performed to compare selected energy technologies to MFU-V for noninvasive face and body skin tightening, in particular, among Asian patients. This was supplemented with internal documents to provide evidence and support arguments if no peer-reviewed data were available. RESULTS: We highlighted the differences between devices and platforms and identified factors requiring attention and caution. Due to the increase in new devices lacking strong supporting clinical evidence of both safety and efficacy in Asia, it is necessary to convene physicians with substantial experience in MFU-V and devise a consensus on Asian patient selection, treatment planning, and customization. CONCLUSION: Many platforms duplicate or claim similar technologies, efficacy, or safety without significant peer-reviewed scientific or clinical evidence. We showed that MFU-V satisfies this clinical imperative. Further, the patented DeepSEE® technology allows users to noninvasively "see" through the skin to ensure treatment precision, facilitate optimal skin lifting and tightening, and enhance patient comfort and safety. Therefore, we believe that MFU-V is the gold standard for nonsurgical lifting and skin tightening.
  8. Song Z, Zhang W, Jiang Q, Deng L, Du L, Mou W, et al.
    Int J Surg, 2023 Dec 01;109(12):3848-3860.
    PMID: 37988414 DOI: 10.1097/JS9.0000000000000862
    BACKGROUND: The early detection of high-grade prostate cancer (HGPCa) is of great importance. However, the current detection strategies result in a high rate of negative biopsies and high medical costs. In this study, the authors aimed to establish an Asian Prostate Cancer Artificial intelligence (APCA) score with no extra cost other than routine health check-ups to predict the risk of HGPCa.

    PATIENTS AND METHODS: A total of 7476 patients with routine health check-up data who underwent prostate biopsies from January 2008 to December 2021 in eight referral centres in Asia were screened. After data pre-processing and cleaning, 5037 patients and 117 features were analyzed. Seven AI-based algorithms were tested for feature selection and seven AI-based algorithms were tested for classification, with the best combination applied for model construction. The APAC score was established in the CH cohort and validated in a multi-centre cohort and in each validation cohort to evaluate its generalizability in different Asian regions. The performance of the models was evaluated using area under the receiver operating characteristic curve (ROC), calibration plot, and decision curve analyses.

    RESULTS: Eighteen features were involved in the APCA score predicting HGPCa, with some of these markers not previously used in prostate cancer diagnosis. The area under the curve (AUC) was 0.76 (95% CI:0.74-0.78) in the multi-centre validation cohort and the increment of AUC (APCA vs. PSA) was 0.16 (95% CI:0.13-0.20). The calibration plots yielded a high degree of coherence and the decision curve analysis yielded a higher net clinical benefit. Applying the APCA score could reduce unnecessary biopsies by 20.2% and 38.4%, at the risk of missing 5.0% and 10.0% of HGPCa cases in the multi-centre validation cohort, respectively.

    CONCLUSIONS: The APCA score based on routine health check-ups could reduce unnecessary prostate biopsies without additional examinations in Asian populations. Further prospective population-based studies are warranted to confirm these results.

  9. Park JY, Ngan HY, Park W, Cao Z, Wu X, Ju W, et al.
    J Gynecol Oncol, 2015 Jan;26(1):68-74.
    PMID: 25609163 DOI: 10.3802/jgo.2015.26.1.68
    The Asian Society of Gynecologic Oncology International Workshop 2014 on gynecologic oncology was held in Asan Medical Center, Seoul, Korea on the 23rd to 24th August 2014. A total of 179 participants from 17 countries participated in the workshop, and the up-to-date findings on the management of gynecologic cancers were presented and discussed. This meeting focused on the new trends in the management of cervical cancer, fertility-sparing management of gynecologic cancers, surgical management of gynecologic cancers, and recent advances in translational research on gynecologic cancers.
  10. Salmon C, Song L, Muir K, UKGPCS Collaborators, Pashayan N, Dunning AM, et al.
    Eur J Epidemiol, 2021 Sep;36(9):913-925.
    PMID: 34275018 DOI: 10.1007/s10654-021-00781-1
    While being in a committed relationship is associated with a better prostate cancer prognosis, little is known about how marital status relates to its incidence. Social support provided by marriage/relationship could promote a healthy lifestyle and an increased healthcare seeking behavior. We investigated the association between marital status and prostate cancer risk using data from the PRACTICAL Consortium. Pooled analyses were conducted combining 12 case-control studies based on histologically-confirmed incident prostate cancers and controls with information on marital status prior to diagnosis/interview. Marital status was categorized as married/partner, separated/divorced, single, or widowed. Tumours with Gleason scores ≥ 8 defined high-grade cancers, and low-grade otherwise. NCI-SEER's summary stages (local, regional, distant) indicated the extent of the cancer. Logistic regression was used to derive odds ratios (ORs) and 95% confidence intervals (CI) for the association between marital status and prostate cancer risk, adjusting for potential confounders. Overall, 14,760 cases and 12,019 controls contributed to analyses. Compared to men who were married/with a partner, widowed men had an OR of 1.19 (95% CI 1.03-1.35) of prostate cancer, with little difference between low- and high-grade tumours. Risk estimates among widowers were 1.14 (95% CI 0.97-1.34) for local, 1.53 (95% CI 1.22-1.92) for regional, and 1.56 (95% CI 1.05-2.32) for distant stage tumours. Single men had elevated risks of high-grade cancers. Our findings highlight elevated risks of incident prostate cancer among widowers, more often characterized by tumours that had spread beyond the prostate at the time of diagnosis. Social support interventions and closer medical follow-up in this sub-population are warranted.
  11. Butt J, Jenab M, Pawlita M, Tjønneland A, Kyrø C, Boutron-Ruault MC, et al.
    Cancer Epidemiol Biomarkers Prev, 2020 Jul;29(7):1475-1481.
    PMID: 32332031 DOI: 10.1158/1055-9965.EPI-19-1545
    BACKGROUND: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing H. pylori and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    METHODS: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer.

    RESULTS: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99-1.82), the latter being nonstatistically significant only in the fully adjusted model.

    CONCLUSIONS: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer.

    IMPACT: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence.

  12. Huang J, Zagai U, Hallmans G, Nyrén O, Engstrand L, Stolzenberg-Solomon R, et al.
    Int J Cancer, 2017 Apr 15;140(8):1727-1735.
    PMID: 28032715 DOI: 10.1002/ijc.30590
    The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction 
  13. Kim DS, Yoon YI, Kim BK, Choudhury A, Kulkarni A, Park JY, et al.
    Hepatol Int, 2024 Apr;18(2):299-383.
    PMID: 38416312 DOI: 10.1007/s12072-023-10629-3
    Liver transplantation is a highly complex and challenging field of clinical practice. Although it was originally developed in western countries, it has been further advanced in Asian countries through the use of living donor liver transplantation. This method of transplantation is the only available option in many countries in the Asia-Pacific region due to the lack of deceased organ donation. As a result of this clinical situation, there is a growing need for guidelines that are specific to the Asia-Pacific region. These guidelines provide comprehensive recommendations for evidence-based management throughout the entire process of liver transplantation, covering both deceased and living donor liver transplantation. In addition, the development of these guidelines has been a collaborative effort between medical professionals from various countries in the region. This has allowed for the inclusion of diverse perspectives and experiences, leading to a more comprehensive and effective set of guidelines.
  14. Matejcic M, Saunders EJ, Dadaev T, Brook MN, Wang K, Sheng X, et al.
    Nat Commun, 2019 01 17;10(1):382.
    PMID: 30655571 DOI: 10.1038/s41467-019-08293-z
    The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.
  15. Brandão A, Paulo P, Maia S, Pinheiro M, Peixoto A, Cardoso M, et al.
    Cancers (Basel), 2020 Nov 04;12(11).
    PMID: 33158149 DOI: 10.3390/cancers12113254
    The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
  16. Huynh-Le MP, Karunamuni R, Fan CC, Asona L, Thompson WK, Martinez ME, et al.
    Prostate Cancer Prostatic Dis, 2022 Apr;25(4):755-761.
    PMID: 35152271 DOI: 10.1038/s41391-022-00497-7
    BACKGROUND: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.

    METHODS: In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.

    RESULTS: The final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.

    CONCLUSIONS: We demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.

  17. Matejcic M, Saunders EJ, Dadaev T, Brook MN, Wang K, Sheng X, et al.
    Nat Commun, 2018 Nov 05;9(1):4616.
    PMID: 30397198 DOI: 10.1038/s41467-018-06863-1
    Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p 
  18. Karunamuni RA, Huynh-Le MP, Fan CC, Thompson W, Eeles RA, Kote-Jarai Z, et al.
    Prostate Cancer Prostatic Dis, 2021 Jun;24(2):532-541.
    PMID: 33420416 DOI: 10.1038/s41391-020-00311-2
    BACKGROUND: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).

    MATERIALS AND METHOD: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.

    RESULTS: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.

    CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

  19. Adams CD, Richmond R, Ferreira DLS, Spiller W, Tan V, Zheng J, et al.
    Cancer Epidemiol Biomarkers Prev, 2019 Jan;28(1):208-216.
    PMID: 30352818 DOI: 10.1158/1055-9965.EPI-18-0079
    BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

    METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

    RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.

    CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.

    IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

  20. Huynh-Le MP, Fan CC, Karunamuni R, Thompson WK, Martinez ME, Eeles RA, et al.
    Nat Commun, 2021 02 23;12(1):1236.
    PMID: 33623038 DOI: 10.1038/s41467-021-21287-0
    Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p 
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