Chronic hepatitis infection is associated with extrahepatic cancer development: a nationwide population-based study in Taiwan

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the major causes of chronic hepatitis infection (CHI). This longitudinal cohort study investigated the association of CHI with hepatic and extrahepatic cancer development in Taiwan. Methods: Patients with HBV infection and HCV infection were identified from the Taiwan National Health Insurance Research Database. A Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) for determining the association between CHI and cancer development. Results: The patients with HBV infection exhibited an increased risk of colorectal cancer (HR: 1.36, 95 % CI: 1.09–1.70), liver cancer (HR: 21.47, 95 % CI: 18.0–25.6), gallbladder and extrahepatic bile duct cancer (HR: 2.05, 95 % CI: 1.07–3.91), pancreatic cancer (HR: 2.61, 95 % CI: 1.47–4.61), kidney cancer (HR: 1.72, 95 % CI: 1.10–2.68), ovarian cancer (HR: 2.31, 95 % CI: 1.21–4.39), and non-Hodgkin’s lymphoma (HR: 2.10, 95 % CI: 1.25–3.52). The patients with HCV infection exhibited an increased risk of liver cancer (HR: 25.10, 95 % CI: 20.9–30.2), gallbladder and extrahepatic bile duct cancer (HR: 2.60, 95 % CI: 1.42–4.73), ovarian cancer (HR: 5.15, 95 % CI: 1.98–13.4), and non-Hodgkin’s lymphoma (HR: 2.30, 95 % CI: 1.34–3.96). Conclusion: The present population-based study revealed that in addition to its association with primary liver cancer, CHI is associated with an increased risk of extrahepatic cancer

Non-communicable diseases pandemic and precision medicine: Is Africa ready?

Non-communicable diseases (NCDs) kill more than 41 million people every year, accounting for 71% of all deaths globally. The prevalence of NCDs is estimated to be higher than that of infectious diseases in Africa by 2030. Precision medicine may help with early identification of cases, resulting in timely prevention and improvement in the efficacy of treatments. However, Africa has been lagging behind in genetic research, a key component of the precision medicine initiative. A number of genomic research initiatives which could lead to translational genomics are emerging on the African continent which includes the Non-communicable Diseases Genetic Heritage Study (NCDGHS) and the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network. These offer a promise that precision medicine can be applied in African countries. This review evaluates the advances of genetic studies for cancer, hypertension, type 2 diabetes and body mass index (BMI) in Africa

Hepatitis B infection is causally associated with extrahepatic cancers: A Mendelian randomization study.

BACKGROUND: Evidence from observational studies suggests that chronic hepatitis B virus (HBV) infection is associated with extrahepatic cancers. However, the causal association between chronic HBV infection and extrahepatic cancers remains to be determined. METHODS: We performed two-sample Mendelian randomization (MR) to investigate whether chronic HBV infection is causally associated with extrahepatic cancers. We identified four independent genetic variants strongly associated (P-value < 5 × 10-8) with the exposure, chronic HBV infection in 1371 cases and 2938 controls of East Asian ancestry in Korea, which were used as instrumental variables. Genome-wide association summary level data for outcome variables, that included cancer of the biliary tract, cervix, colorectum, endometrium, esophagus, gastric, hepatocellular carcinoma, lung, ovary and pancreas were obtained from Biobank Japan. FINDINGS: Using the multivariable inverse variance weighted method, we found genetic liability to chronic HBV infection causally associated with extrahepatic cancers including cervical cancer (odds ratio [OR] = 1.57, 95% confidence interval [CI] = 1.29-1.91, P-value = 0.0001) and gastric cancer (OR = 1.12, 95% CI = 1.05-1.19, P-value = 0.0001). Moreover, chronic HBV infection (OR = 1.20, 95% CI = 1.07-1.34, P-value = 0.0021) was causally associated with hepatocellular carcinoma, supporting a well-established association between chronic HBV infection and hepatocellular carcinoma. INTERPRETATION: Our MR analysis revealed that chronic HBV infection is causally associated with extrahepatic cancers including cervical and gastric cancers. FUNDING: None

Genetic loci implicated in meta-analysis of body shape in Africans.

BACKGROUND AND AIMS: Obesity is one of the leading causes of non-communicable diseases (NCD). Thus, NCD risk varies in obese individuals based on the location of their fat depots; while subcutaneous adiposity is protective, visceral adiposity increases NCD risk. Although, previously anthropometric traits have been used to quantify body shape in low-income settings, there is no consensus on how it should be assessed. Hence, there is a growing interest to evaluate body shape derived from the principal component analysis (PCA) of anthropometric traits; however, this is yet to be explored in individuals of African ancestry whose body shape is different from those of Europeans. We set out to capture body shape in its multidimensional structure and examine the association between genetic variants and body shape in individuals of African ancestry. METHOD AND RESULTS: We performed a genome-wide association study (GWAS) for body shape derived from PCA analysis of anthropometric traits in the Ugandan General Population Cohort (GPC, n = 6407) and the South African Zulu Cohort (SZC, n = 2595), followed by a GWAS meta-analysis to assess the genetic variants associated with body shape. We identified variants in FGF12, GRM8, TLX1NB and TRAP1 to be associated with body shape. These genes were different from the genes been associated with BMI, height, weight, WC and waist-hip ration in continental Africans. Notably, we also observed that a standard deviation change in body shape was associated with an increase in blood pressure and blood lipids. CONCLUSION: Variants associated with body shape, as a composite variable might be different for those of individual anthropometric traits. Larger studies are required to further explore these phenomena

HPV types 16/18 L1 E6 and E7 proteins seropositivity and cervical cancer risk in HIV-positive and HIV-negative black South African women

BACKGROUND: In populations with high rates of human immunodeficiency virus (HIV)-coinfection, the nature of the relationship between human papillomavirus (HPV)-16 and -18 (L1, E6 and E7) antibodies and cervical cancer is still uncertain. We measured the association between seropositivity to HPV (L1, E6 and E7) proteins and cervical cancer among black South African women with and without HIV co-infection. METHODS: We used questionnaire data and serum collected from consecutively recruited patients with a newly diagnosed cancer from the Johannesburg Cancer Study from 1346 cervical cancer cases and 2532 controls (diagnosed with other non-infection related cancers). Seropositivity to HPV proteins was measured using a multiplex serological assay based on recombinant glutathione S-transferase (GST) fusion proteins. We measured associations between their presence and cervical cancer using unconditional logistic regression models and evaluated the sensitivity and specificity of these HPV biomarkers. RESULTS: Among controls, HIV-negative women from rural areas compared to urban had significantly higher HPV seroprevalence, HPV16 E7 (8.6% vs 3.7%) and HPV18 E7 (7.9% vs 2.0%). HPV16 E6 and E7 antibodies were positively associated with cervical cancer in HIV-positive (Adjusted Odds Ratio (AOR) = 33; 95% CI 10-107) and HIV-negative women (AOR = 97; 95% CI 46-203). In HIV-positive women, HPV E6/E7 antibodies had low sensitivity (43.0%) and high specificity (90.6%) for cervical cancer detection. In HIV-negative women, HPV E6/E7 antibodies sensitivity was 70.6% and specificity was 89.7%. CONCLUSIONS: Our data show that HPV (L1, especially E6 and E7) antibody positivity is associated with cervical cancer in both HIV-positive and HIV-negative women. Nonetheless, being HIV-positive plays an important role in the development of cervical cancer

Ranking lifestyle risk factors for cervical cancer among black women : A case-control study from Johannesburg, South Africa

BACKGROUND: Aside from human papillomavirus (HPV), the role of other risk factors in cervical cancer such as age, education, parity, sexual partners, smoking and human immunodeficiency virus (HIV) have been described but never ranked in order of priority. We evaluated the contribution of several known lifestyle co-risk factors for cervical cancer among black South African women. METHODS: We used participant data from the Johannesburg Cancer Study, a case-control study of women recruited mainly at Charlotte Maxeke Johannesburg Academic Hospital between 1995 and 2016. A total of 3,450 women in the study had invasive cervical cancers, 95% of which were squamous cell carcinoma. Controls were 5,709 women with cancers unrelated to exposures of interest. Unconditional logistic regression models were used to calculate adjusted odds ratios (ORadj) and 95% confidence intervals (CI). We ranked these risk factors by their population attributable fractions (PAF), which take the local prevalence of exposure among the cases and risk into account. RESULTS: Cervical cancer in decreasing order of priority was associated with (1) being HIV positive (ORadj = 2.83, 95% CI = 2.53-3.14, PAF = 17.6%), (2) lower educational attainment (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 16.2%), (3) higher parity (3+ children vs 2-1 children (ORadj = 1.25, 95% CI = 1.07-1.46, PAF = 12.6%), (4) hormonal contraceptive use (ORadj = 1.48, 95% CI = 1.24-1.77, PAF = 8.9%), (5) heavy alcohol consumption (ORadj = 1.44, 95% CI = 1.15-1.81, PAF = 5.6%), (6) current smoking (ORadj = 1.64, 95% CI = 1.41-1.91, PAF = 5.1%), and (7) rural residence (ORadj = 1.60, 95% CI = 1.44-1.77, PAF = 4.4%). CONCLUNSION: This rank order of risks could be used to target educational messaging and appropriate interventions for cervical cancer prevention in South African women

Usefulness of high-risk HPV early oncoprotein (E6 and E7) serological markers in the detection of cervical cancer : A systematic review and meta-analysis

Abstract We reviewed the literature on the importance of selected anti-high-risk human papillomavirus (HR-HPV) antibodies (namely, 16/18 and early oncoproteins E6 and E7) as potential serological markers for early detection of individuals at high risk of cervical cancer. We searched for studies in PubMed and Embase databases published from 2010 to 2020 on antibodies against HR-HPV E6 and E7 early proteins and cervical cancer. Pooled sensitivity and specificity for HPV16 and HPV18 antibodies were calculated using a bivariate hierarchical random-effects model. A total of 69 articles were identified; we included three studies with 1550 participants. For the three HPV16/18 E6 and E7 antibody tests, enzyme-linked immunosorbent assay-based assays had a sensitivity of 18+ (95CI]: 15–21) and a specificity of 9695 92–98), for slot-blot, sensitivity was 28.995 23.3–35.1) and specificity was 7295 66.6–77.0) for detecting CIN2+, and for multiplex HPV serology assay based on a glutathione S-transferase, sensitivity was 1695 8.45–28.6) and specificity was 9895 97–99) for detecting invasive cervical cancer. HR-HPV16/18 E6 and E7 serological markers showed high specificity, but sensitivity was suboptimal for the detection of cervical cancer in either population screening settings or as point-of-care screening tests

Multi-trait discovery and fine-mapping of lipid loci in 125,000 individuals of African ancestry.

Most genome-wide association studies (GWAS) for lipid traits focus on the separate analysis of lipid traits. Moreover, there are limited GWASs evaluating the genetic variants associated with multiple lipid traits in African ancestry. To further identify and localize loci with pleiotropic effects on lipid traits, we conducted a genome-wide meta-analysis, multi-trait analysis of GWAS (MTAG), and multi-trait fine-mapping (flashfm) in 125,000 individuals of African ancestry. Our meta-analysis and MTAG identified four and 14 novel loci associated with lipid traits, respectively. flashfm yielded an 18% mean reduction in the 99% credible set size compared to single-trait fine-mapping with JAM. Moreover, we identified more genetic variants with a posterior probability of causality >0.9 with flashfm than with JAM. In conclusion, we identified additional novel loci associated with lipid traits, and flashfm reduced the 99% credible set size to identify causal genetic variants associated with multiple lipid traits in African ancestry