Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction

EFEKTIVITAS PENGAWASAN UNIT KERJA ANTI FRAUD PADA BANK MUAMALAT INDONESIA

Perkembangan perbankan syari‟ah di Indonesia demikian pesat yang ditandai dengan berdirinya Bank Muamalat Indonesia. Perkembangan ini berimplikasi pada besarnya tantangan perbankan syari‟ah di Indonesia terutama dalam mempertahankan identitasnya sebagai perusahaan yang bergerak berlandaskan prinsip-prinsip syari‟ah. Sejak berdirinya perbankan syariah,berbagai kontroversi muncul dari masyarakat, masalah yang paling banyak disorot adalah pelekatan label syariah pada institusi keuangan Islam yang masih dianggap belum layak. Keraguan masyarakat tersebut seolah terjawab dengan munculnya kasus yang cukup menggemparkan yakni kasus fraud (tindak kecurangan) yang terjadi di lembaga syariah. Bank Muamalat Indonesia merupakan bank syari‟ah pertama yang muncul dengan gagasan bank murni syari‟ah. Akan tetapi, bank Muamalat Indonesia juga tak luput dari kasus fraud yang dilakukan oleh karyawan bank tersebut. Berdasarkan Laporan Tahunan BMI menyebutkan bahwa telah terjadi peningkatan kasus fraud dari tahun sebelumnya yang berjumlah 18 kasus menjadi 82 kasus pada tahun 2016. Padahal perusahaan yang menggunakan identitas syariah seharusnya dapat lebih meminimalisir bahkan meniadakan resiko terjadinya kasus fraud dengan adanya internal control perusahaan. Dari latar belakang tersebut, peneliti berusaha mendalami peran pengawasan Unit Kerja Anti Fraud dalam fraud preventive pada Bank Muamalat Indonesia. Penelitian ini merupakan penelitin pustaka yang bersifat deskriptif analisis dengan pendekatan kualitatif. Adapun sumber bahan hukum primer yang dipakai yaitu berdasarkan Laporan Tahunan Bank Muamalat Indonesia Tahun 2016. Sedangkan sumber bahan hukum sekunder berupa buku-buku, jurnal,karya ilmiah, artikel, terkait dengan strategi anti fraud perbankan syariah. Dari hasil penelitian dikemukakan bahwa peningkatan kasus fraud yang terjadi pada Bank Muamalat Indonesia disebabkan kurang efektifnya pengawasan Unit Kerja Anti Fraud. Hal ini dikarenakan kegiatan yang dilakukan selama tahun 2016 belum menujukkan adanya usaha preventif terhadap kasus fraud. Sedangkan pencegahan merupakan pilar penting dalam keefektivan sebuah pengawasan. Tujuan perusahaan dalam mencegah fraud dapat tercapai, jika fungsi pengawasan dilakukan sebelum terjadinya penyimpangan-penyimpangan sehingga lebih bersifat mencegah (prefentive control). Oleh karena itu, keefektivan pengawasan Unit Kerja Anti Fraud diharapkan dapat meminimalisir tindak kecurangan demi mewujudkan perusahaan yang patuh terhadap ketentuan syariah sesuai dengan identitas perusahaan. vii Usaha pencegahan terjadinya kasus pada Bank Muamalat Indonesia diharapkan dapat menjadi bukti terlaksananya tatakelola perusahaan (Good Corporate Governance) pada Bank Syari‟ah dengan baik. Hal ini berdasarkan dalam dalam perbankan syariah dikenal adanya prinsip-prinsip syariah yang mendukung bagi terlaksananya prinsip GCG yakni keharusan bagi subjek hukum termasuk bank untuk menerapkan prinsip kejujuran (shiddiq), edukasi kepada masyarakat (tabligh), kepercayaan (amanah), dan pengelolaan secara profesional (fathanah)

Differential burden of rare and common variants on tumor characteristics, survival, and mode of detection in breast cancer

Genetic variants that increase breast cancer risk can be rare or common. This study tests whether the genetic risk stratification of breast cancer by rare and common variants in established loci can discriminate tumors with different biology, patient survival, and mode of detection. Multinomial logistic regression tested associations between genetic risk load [protein-truncating variant (PTV) carriership in 31 breast cancer predisposition genes—or polygenic risk score (PRS) using 162 single-nucleotide polymorphisms], tumor characteristics, and mode of detection (OR). Ten-year breast cancer–specific survival (HR) was estimated using Cox regression models. In this unselected cohort of 5,099 patients with breast cancer diagnosed in Sweden between 2001 and 2008, PTV carriers (n = 597) were younger and associated with more aggressive tumor phenotypes (ER-negative, large size, high grade, high proliferation, luminal B, and basal-like subtype) and worse outcome (HR, 1.65; 1.16–2.36) than noncarriers. After excluding 92 BRCA1/2 carriers, PTV carriership remained associated with high grade and worse survival (HR, 1.76; 1.21–2.56). In 5,007 BRCA1/2 noncarriers, higher PRS was associated with less aggressive tumor characteristics (ER-positive, PR-positive, small size, low grade, low proliferation, and luminal A subtype). Among patients with low mammographic density (Significance: These findings offer the potential to improve screening practices for breast cancer by providing a deeper understanding of how risk variants affect disease progression and mode of detection

Differential burden of rare and common variants on tumor characteristics, survival, and mode of detection in breast cancer

Genetic variants that increase breast cancer risk can be rare or common. This study tests whether the genetic risk stratification of breast cancer by rare and common variants in established loci can discriminate tumors with different biology, patient survival, and mode of detection. Multinomial logistic regression tested associations between genetic risk load [protein-truncating variant (PTV) carriership in 31 breast cancer predisposition genes—or polygenic risk score (PRS) using 162 single-nucleotide polymorphisms], tumor characteristics, and mode of detection (OR). Ten-year breast cancer–specific survival (HR) was estimated using Cox regression models. In this unselected cohort of 5,099 patients with breast cancer diagnosed in Sweden between 2001 and 2008, PTV carriers (n = 597) were younger and associated with more aggressive tumor phenotypes (ER-negative, large size, high grade, high proliferation, luminal B, and basal-like subtype) and worse outcome (HR, 1.65; 1.16–2.36) than noncarriers. After excluding 92 BRCA1/2 carriers, PTV carriership remained associated with high grade and worse survival (HR, 1.76; 1.21–2.56). In 5,007 BRCA1/2 noncarriers, higher PRS was associated with less aggressive tumor characteristics (ER-positive, PR-positive, small size, low grade, low proliferation, and luminal A subtype). Among patients with low mammographic density (<25%), non-BRCA1/2 PTV carriers were more often interval than screen-detected breast cancer (OR, 1.89; 1.12–3.21) than noncarriers. In contrast, higher PRS was associated with lower risk of interval compared with screen-detected cancer (OR, 0.77; 0.64–0.93) in women with low mammographic density. These findings suggest that rare and common breast cancer susceptibility loci are differentially associated with tumor characteristics, survival, and mode of detection. Significance: These findings offer the potential to improve screening practices for breast cancer by providing a deeper understanding of how risk variants affect disease progression and mode of detection

Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort

Breast cancer patients with BRCA1/2‐driven tumors may benefit from targeted therapy. It is not clear whether current BRCA screening guidelines are effective at identifying these patients. The purpose of our study was to evaluate the prevalence of inherited BRCA1/2 pathogenic variants in a large, clinically representative breast cancer cohort and to estimate the proportion of BRCA1/2 carriers not detected by selectively screening individuals with the highest probability of being carriers according to current clinical guidelines. The study included 5,122 unselected Swedish breast cancer patients diagnosed from 2001 to 2008. Target sequence enrichment (48.48 Fluidigm Access Arrays) and sequencing were performed (Illumina Hi‐Seq 2,500 instrument, v4 chemistry). Differences in patient and tumor characteristics of BRCA1/2 carriers who were already identified as part of clinical BRCA1/2 testing routines and additional BRCA1/2 carriers found by sequencing the entire study population were compared using logistic regression models. Ninety‐two of 5,099 patients with valid variant calls were identified as BRCA1/2 carriers by screening all study participants (1.8%). Only 416 study participants (8.2%) were screened as part of clinical practice, but this identified 35 out of 92 carriers (38.0%). Clinically identified carriers were younger, less likely postmenopausal and more likely to be associated with familiar ovarian cancer compared to the additional carriers identified by screening all patients. More BRCA2 (34/42, 81.0%) than BRCA1 carriers (23/50, 46%) were missed by clinical screening. In conclusion, BRCA1/2 mutation prevalence in unselected breast cancer patients was 1.8%. Six in ten BRCA carriers were not detected by selective clinical screening of individuals

Prevalence of BRCA1 and BRCA2 pathogenic variants in a large, unselected breast cancer cohort

Breast cancer patients with BRCA1/2‐driven tumors may benefit from targeted therapy. It is not clear whether current BRCA screening guidelines are effective at identifying these patients. The purpose of our study was to evaluate the prevalence of inherited BRCA1/2 pathogenic variants in a large, clinically representative breast cancer cohort and to estimate the proportion of BRCA1/2 carriers not detected by selectively screening individuals with the highest probability of being carriers according to current clinical guidelines. The study included 5,122 unselected Swedish breast cancer patients diagnosed from 2001 to 2008. Target sequence enrichment (48.48 Fluidigm Access Arrays) and sequencing were performed (Illumina Hi‐Seq 2,500 instrument, v4 chemistry). Differences in patient and tumor characteristics of BRCA1/2 carriers who were already identified as part of clinical BRCA1/2 testing routines and additional BRCA1/2 carriers found by sequencing the entire study population were compared using logistic regression models. Ninety‐two of 5,099 patients with valid variant calls were identified as BRCA1/2 carriers by screening all study participants (1.8%). Only 416 study participants (8.2%) were screened as part of clinical practice, but this identified 35 out of 92 carriers (38.0%). Clinically identified carriers were younger, less likely postmenopausal and more likely to be associated with familiar ovarian cancer compared to the additional carriers identified by screening all patients. More BRCA2 (34/42, 81.0%) than BRCA1 carriers (23/50, 46%) were missed by clinical screening. In conclusion, BRCA1/2 mutation prevalence in unselected breast cancer patients was 1.8%. Six in ten BRCA carriers were not detected by selective clinical screening of individuals