The association between hepatic viral infections and cancers: a cross-sectional study in the Taiwan adult population.

BACKGROUND: Hepatitis B (HBV) and hepatitis C (HCV) viruses are diseases of global public health concern and are associated with liver cancer. Recent studies have revealed associations between hepatic viral infections and extrahepatic cancers. This study aimed to explore the associations between hepatitis B and C viruses and cancer at baseline in the Taiwan Biobank database while controlling for a wide range of confounding variables. METHODS: In a cross-sectional study of adults aged > 20 years, we compared the distribution of demographic factors, lifestyle, and comorbidities between viral and nonviral hepatic groups using the chi-square test. Univariate and multivariate logistic regressions were performed to observe the associations between hepatitis B and C viral infections and cancers by estimating the odds ratio (OR) and 95% confidence interval (CI). Multivariate regression analysis was adjusted for sociodemographic factors, lifestyle, and comorbidities. RESULTS: From the database, 2955 participants were identified as having HCV infection, 15,305 as having HBV infection, and 140,108 as the nonviral group. HBV infection was associated with an increased likelihood of liver cancer (adjusted OR (aOR) = 6.60, 95% CI = 3.21-13.57, P < 0.001) and ovarian cancer (aOR = 4.63, 95% CI = 1.98-10.83, P = 0.001). HCV infection was observed to increase the likelihood of liver cancer (aOR = 4.90, 95% CI = 1.37-17.53, P = 0.015), ovarian cancer (aOR = 8.50, 95% CI = 1.78-40.69, P = 0.007), and kidney cancer (aOR = 12.89, 95% CI = 2.41-69.01, P = 0.003). CONCLUSION: Our findings suggest that hepatic viral infections are associated with intra- and extrahepatic cancers. However, being cross-sectional, causal inferences cannot be made. A recall-by-genotype study is recommended to further investigate the causality of these associations.

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.

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

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% for detecting CIN2+ (95% confidence interval [CI]: 15-21) and a specificity of 96% (95% CI: 92-98), for slot-blot, sensitivity was 28.9% (95% CI: 23.3-35.1) and specificity was 72% (95% CI: 66.6-77.0) for detecting CIN2+, and for multiplex HPV serology assay based on a glutathione S-transferase, sensitivity was 16% (95% CI: 8.45-28.6) and specificity was 98% (95% CI: 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.

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.

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.

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.

Cumulative risks of colorectal cancer in Han Chinese patients with Lynch syndrome in Taiwan.

Patients with Lynch syndrome have a high risk of colorectal cancer (CRC). In this study, we estimated the age- and sex-specific cumulative risks of CRC in Han Chinese patients with Lynch syndrome caused by the pathogenic germline mutations in MLH1 or MSH2 in Taiwan. Based on 321 mutation carriers and 419 non-mutation carriers from 75 pedigrees collected in an Amsterdam criteria family registry in Taiwan, the age- and sex-specific cumulative risks of CRC in male carriers of mutation in MLH1 and MSH2 at the age of 70 years were 60.3% (95% confidence interval (CI) = 31.1%-89.9%) and 76.7% (95% CI = 37.2%-99.0%), respectively. For females, the cumulative risks of CRC at the age of 70 were estimated to be 30.6% (95% CI = 14.3%-57.7%) and 49.3% (95% CI = 21.9%-84.5%) in the carriers of MLH1 and MSH2 germline mutations, respectively. In conclusion, the cumulative risks of CRC at the age of 70 in the Han Chinese patients is higher in mutation carriers than non-mutation carriers and male mutation carriers have a higher cumulative risk of developing CRC than the female mutation carriers.

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.

HLA-DRB1 alleles and cervical cancer: A meta-analysis of 36 case-control studies.

BACKGROUND: Human leukocyte antigens (HLA) are encoded by closely linked genetic loci, and are important in cervical carcinogenesis. The association between HLA-DRB1 alleles with cervical cancer has been studied extensively, but results reported thus far have been inconsistent. Hence, we performed a meta-analysis to precisely assess this association. METHODS: A literature search was conducted in various online databases to identify suitable articles. Case-control studies investigating the association between HLA-DRB1 alleles and cervical cancer were included in this study. Fixed and random-effect models were used to calculate the pooled odds ratio (OR) and 95% confidence intervals (CIs). RESULTS: A total of 6645 cases and 9095 controls from 36 case-control studies were included. Of the 13 HLA-DRB1 family alleles, DRB1*09 (OR = 1.30) and DRB1 *15 (OR = 1.60) were associated with cervical cancer risk, whilst DRB1*13 (OR = 0.66) exerted a protective effect. Among the 44 HLA-DRB1 specific alleles, DRB1*04:01 (OR = 1.25), DRB1*10:01 (OR = 1.45), DRB1*11:01 (OR = 1.32), DRB1*15:01 (OR = 1.21) and DRB1*15:02 (OR = 1.55) were associated with an increased risk of cervical cancer. However, DRB1*04:06 (OR = 0.52), DRB1*12:02 (OR = 0.61), DRB1*13:01 (OR = 0.62), DRB1*13:02 (OR = 0.57), and DRB1*14:04 (OR = 0.37) were associated with a decreased risk of cervical cancer. Subgroup analysis also revealed that HLA-DRB1 alleles are associated with cervical cancer in Asian, Caucasian, Hispanic or Latin American and black sub-Saharan Africa populations. CONCLUSION: Our meta-analysis revealed that multiple HLA-DRB1 alleles are associated with cervical cancer in women of diverse ancestry populations.

Association of TP53 rs1042522 with cervical cancer in the sub-Saharan African population: a meta-analysis.

OBJECTIVE: TP53 plays a crucial role in preventing cancer development. Previous studies in sub-Saharan Africa (SSA) reported inconclusive findings for the association of the TP53 rs1042522 C > G variant with cervical cancer. We therefore performed a meta-analysis to summarise this association in the SSA population. METHODS: Online databases were searched to identify suitable articles according to the PRISMA guidelines. We included studies published in English or French that provided the sample sizes and genotype counts for both cases and controls and evaluated the association between TP53 rs1042522 and cervical cancer in the SSA population. A fixed-effect model was used to calculate the pooled odds ratio (OR) and 95% confidence intervals (95% CIs). RESULTS: A total of 699 cervical cancer cases and 1008 controls from eight studies in SSA were included in this meta-analysis. Women harbouring the variant G allele of the TP53 rs1042522 were at increased risk of cervical cancer in allelic (G vs. C; OR = 1.30, 95% Cl = 1.12-1.50), homozygous (GG vs. CC; OR = 1.62, 95% CI = 1.20-2.19) and recessive (GG vs. CG + GG; OR = 1.74, 95% CI = 1.34-2.25) genetic models. However, the dominant genetic model (CG + GG vs. CC; OR = 1.20, 95% CI = 0.96-1.48) was not significantly associated with cervical cancer. CONCLUSIONS: Our meta-analysis revealed that harbouring variant G allele of TP53 rs1042522 is associated with cervical cancer risk in the SSA population.

OBJECTIF: Le TP53 joue un rôle crucial dans la prévention du développement du cancer. Des études antérieures en Afrique subsaharienne (ASS) ont rapporté des résultats non concluants pour l'association de la variante TP53 rs1042522 C>G avec le cancer du col de l'utérus. Nous avons donc réalisé une méta-analyse pour résumer cette association dans la population SSA. MÉTHODES: Les bases de données en ligne ont été recherchées pour identifier les articles appropriés selon les directives PRISMA. Nous avons inclus des études publiées en anglais ou en français qui ont fourni la taille des échantillons et le nombre de génotypes pour les cas et les témoins et évalué l'association entre TP53 rs1042522 et le cancer du col de l'utérus dans la population SSA. Un modèle à effet fixe a été utilisé pour calculer le rapport de cotes combiné (OR) et les intervalles de confiance à 95% (IC95%). RÉSULTATS: Un total de 699 cas de cancer du col utérin et 1008 témoins de huit études en ASS ont été inclus dans cette méta-analyse. Les femmes hébergeant l'allèle variant G du TP53 rs1042522 présentaient un risque accru de cancer du col de l'utérus chez les modèles génétiques alléliques (G vs C; OR = 1,30, IC95%: 1,12-1,50), homozygotes (GG vs CC; OR = 1,62, IC95%: 1,20-2,19) et récessifs (GG vs.CG + GG; OR = 1,74, IC95%: 1,34-2,25). Cependant, le modèle génétique dominant (CG + GG vs CC; OR = 1,20, IC95%: 0,96-1,48) n'était pas significativement associé au cancer du col utérin. CONCLUSIONS: Notre méta-analyse a révélé que l'hébergement de l'allèle variant G de TP53 rs1042522 est associé au risque de cancer du col de l'utérus dans la population SSA.

Association of chronic hepatitis B virus infection with age-related macular degeneration.

PURPOSE: To study the association between chronic hepatitis B virus (HBV) and age-related macular degeneration (AMD). METHODS: Data used in this retrospective, frequency-matched cohort study were acquired from the Longitudinal Health Insurance Database 2000, which includes medical claims and registration files for 1 000 000 enrolees in the Taiwan National Health Insurance programme. The HBV cohort contained 17 796 patients who received a diagnosis of chronic HBV infection between January 1, 2000 and December 31, 2012. The non-HBV cohort contained 71 184 participants who were frequency-matched by age, sex and year of index date for comparison. Participants were followed until the end of 2013, and those who developed AMD during the study period were identified. A Cox proportional hazards regression model was used to compare the risk of AMD between cohorts. RESULTS: The incidence of any type of AMD in all participants was 3.88 per 1000 person-years (PY; 2.27 per 1000 PY in the HBV cohort; 1.61 per 1000 PY in the non-HBV cohort). Compared with the non-HBV cohort, the adjusted hazard ratio (HR) for any type of AMD in the HBV cohort was 1.41 [95% confidence interval (CI) 1.23-1.63; p < 0.001]. This significant positive association was stronger among patients who exhibited disease progression from nonexudative to exudative AMD (adjusted HR = 1.74, 95% CI: 1.01-2.99). CONCLUSION: Our results suggest that patients with chronic HBV infection in Taiwan have a significantly elevated risk of developing any type of AMD and that HBV infection may accelerate the progression of AMD.

EGFR, SMAD7, and TGFBR2 Polymorphisms Are Associated with Colorectal Cancer in Patients with Lynch Syndrome.

BACKGROUND/AIM: Epidermal growth factor receptor (EGFR), mothers against decapentaplegic homolog 7 (SMAD7) and transforming growth factor betta (TGFB) are crucial for colorectal cancer (CRC) tumorigenesis. This study investigated whether polymorphisms in EGFR, SMAD7, and TGFB are associated with CRC risk in patients with Lynch syndrome. MATERIALS AND METHODS: Genotyping was performed using Sequenom iPLEX MassArray. Association between genetic polymorphisms and CRC was assessed using a weighted Cox proportional hazard model. RESULTS: Patients carrying the AA genotype of EGFR rs2227983 had a significantly higher CRC risk than those carrying the G allele (HR=2.55, 95% CI=1.25-5.17). The dominant model of SMAD7 rs12953717 (CT + TT genotypes) significantly increased CRC risk (HR=2.17, 95% CI=1.12-4.16) when compared to the wild-type CC genotype. Similarly, the GG genotype of TGFBR2 rs6785358 significantly increased the risk of CRC (HR=21.1, 95% CI=5.06-88.1) compared to the AA genotype. CONCLUSION: EGFR, SMAD7, and TGFBR2 are associated with CRC risk in patients with Lynch syndrome.

Polymorphisms of xenobiotic-metabolizing genes and colorectal cancer risk in patients with lynch syndrome: A retrospective cohort study in Taiwan.

Cytochrome P450 (CYP), glutathione-S-transferase (GST), and N-acetyltransferase (NAT) are crucial for metabolism and clearance of xenobiotics. This study investigated whether CYP, GST, and NAT single nucleotide polymorphisms (SNPs) are associated with colorectal cancer (CRC) in patients with Lynch syndrome. The interaction between these SNPs and cigarette smoking or meat consumption was also explored. We identified 270 patients with Lynch syndrome from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence interval (CIs). The GSTA1 rs3957356 TT (HR = 5.36, 95% CI = 2.39-12.0) and CYP1B1 rs1056836 CC (HR = 7.24, 95% CI = 3.51-14.9) were significantly associated with CRC risk when compared to wild-type CC and GG genotypes, respectively. However, the CYP1A1 rs4646903 CC genotype significantly reduced the risk of CRC (HR = 0.33, 95% CI = 0.12-0.89) when compared to TT genotype. Moreover, significant interactions were observed between NAT1 acetylation and CYP1B1 rs1056827 and meat consumption.Our results suggest that xenobiotic-metabolizing SNPs are not only associated with CRC risk in patients with Lynch syndrome in Taiwan but also interact with meat consumption to modify the disease risk. Environ. Mol. Mutagen. 59:69-78, 2018. © 2017 Wiley Periodicals, Inc.

TP53 Polymorphisms and Colorectal Cancer Risk in Patients with Lynch Syndrome in Taiwan: A Retrospective Cohort Study.

BACKGROUND AND AIM: TP53 encodes p53, which has a crucial role in modulating genes that regulate defense against cancer development. This study investigated whether TP53 polymorphisms are associated with colorectal cancer (CRC) in patients with Lynch syndrome and whether TP53 interacts with lifestyle factors to modify CRC risk. METHODS: We identified 260 MLH1 and MSH2 germline mutation carriers from the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A weighted Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association of TP53 polymorphisms with CRC development. RESULTS: The carriers of the variant C allele of rs1042522 were associated with a decreased CRC risk (GC genotype: HR = 0.35, 95% CI = 0.14-0.86; CC genotype: HR = 0.28, 95% CI = 0.13-0.57). In addition, the dominant model of rs1042522 was associated with a decreased CRC risk (HR = 0.32, 95% CI = 0.15-0.67). The CRC risk was decreased in carriers with the CT and TT genotypes of rs12947788 (HR = 0.20, 95% CI = 0.08-0.46 and HR = 0.25, 95% CI = 0.09-0.65, respectively). Moreover, the dominant model of rs12947788 was significantly associated with a decreased CRC risk (HR = 0.21, 95% CI = 0.09-0.46). A haplotype analysis indicated that compared with the most common GC haplotype, the CT haplotype was associated with a decreased CRC risk (HR = 0.26, 95% CI = 0.11-0.59). However, no significant interaction was observed between TP53 polymorphisms and lifestyle factors. CONCLUSION: The study results revealed that the rs1042522 genotype with the C allele and the rs12947788 genotype with the T allele in TP53 were associated with a decreased CRC risk in patients with Lynch syndrome in Taiwan.

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

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.

Risk Factors Associated with Colorectal Cancer in a Subset of Patients with Mutations in MLH1 and MSH2 in Taiwan Fulfilling the Amsterdam II Criteria for Lynch Syndrome.

BACKGROUND AND AIM: Lynch syndrome, caused by germline mutations in mismatch repair genes, is a predisposing factor for colorectal cancer (CRC). This retrospective cohort study investigated the risk factors associated with the development of CRC in patients with MLH1 and MSH2 germline mutations. METHODS: In total, 301 MLH1 and MSH2 germline mutation carriers were identified from the Amsterdam criteria family registry provided by the Taiwan Hereditary Nonpolyposis Colorectal Cancer Consortium. A Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between the risk factors and CRC development. A robust sandwich covariance estimation model was used to evaluate family dependence. RESULTS: Among the total cohort, subjects of the Hakka ethnicity exhibited an increased CRC risk (HR = 1.62, 95% CI = 1.09-2.34); however, those who performed regular physical activity exhibited a decreased CRC risk (HR = 0.62, 95% CI = 0.41-0.88). The CRC risk was enhanced in MLH1 germline mutation carriers, with corresponding HRs of 1.72 (95% CI = 1.16-2.55) and 0.54 (95% CI = 0.34-0.83) among subjects of the Hakka ethnicity and those who performed regular physical activity, respectively. In addition, the total cohort with a manual occupation had a 1.56 times higher CRC risk (95% CI = 1.07-2.27) than did that with a skilled occupation. Moreover, MSH2 germline mutation carriers with blood group type B exhibited an increased risk of CRC development (HR = 2.64, 95% CI = 1.06-6.58) compared with those with blood group type O. CONCLUSION: The present study revealed that Hakka ethnicity, manual occupation, and blood group type B were associated with an increased CRC risk, whereas regular physical activity was associated with a decreased CRC risk in MLH1 and MSH2 germline mutation carriers.