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- Conti, David, V, et al.
(author)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Journal article (peer-reviewed)abstract
- 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. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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- Wang, Anqi, et al.
(author)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Journal article (peer-reviewed)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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- Awungafac, G, et al.
(author)
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Household food insecurity and its association with self-reported male perpetration of intimate partner violence: a survey of two districts in central and western Uganda
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:3, s. e045427-
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Journal article (peer-reviewed)abstract
- This study aimed to determine the lifetime prevalence of male-perpetrated intimate partner violence (IPV), and to assess the association with food insecurity, sociodemographic factors and health risk behaviours in Uganda in the year preceding COVID-19-associated lockdowns.DesignPopulation-based, cross-sectional household survey.SettingUrban, semiurban and rural communities of the Wakiso and Hoima districts in Uganda.ParticipantsA total of N=2014 males aged 13–80 years participated in the survey. The current study included males who reported having ever been in a sexual union and responded to the IPV questions (N=1314).MeasuresData were collected face-to-face from May 2018 to July 2019 using an interviewer-mediated questionnaire. Lifetime IPV perpetration was measured as ‘no physical and/or sexual IPV’, ‘physical’ versus ‘sexual violence only’, and ‘physical and sexual violence’. Past-year food insecurity was measured through the Food Insecurity Experience Scale and categorised into ‘none’, ‘low’ and ‘high’. Multinomial logistic regression was used to determine the crude and adjusted relative risk ratios (aRRRs) of IPV perpetration in relation to self-reported food insecurity, adjusting for sociodemographic and health risk behaviours.ResultsThe prevalence of self-reported lifetime IPV perpetration was 14.6% for physical and 6.5% for sexual violence, while 5.3% reported to have perpetrated both physical and sexual IPV. Most (75.7%) males reported no food insecurity, followed by low (20.7%) and high (3.6%) food insecurity. In adjusted models, food insecurity was associated with increased risk of having perpetrated both physical and sexual violence (aRRR=2.57, 95% CI 1.52 to 4.32). IPV perpetration was also independently associated with having had more than one lifetime sexual partner and drinking alcohol, but not with education level or religion.ConclusionThis study suggests that food insecurity is associated with male IPV perpetration, and more efforts are needed to prevent and mitigate the expected worsening of this situation as a result of the COVID-19 pandemic.
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- Huynh-Le, MP, et al.
(author)
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Polygenic hazard score is associated with prostate cancer in multi-ethnic populations
- 2021
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1236-
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Journal article (peer-reviewed)abstract
- 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 < 10−180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.
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