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1.
Kari Hemminki Kristina Sundquist Jan Sundquist Asta Försti Vaclav Liska Akseli Hemminki Xinjun Li 《International journal of cancer. Journal international du cancer》2023,152(6):1107-1114
Many environmental risk factors for hepatobiliary cancers are known but whether they are associated with specific cancer types is unclear. We present here a novel approach of assessing standardized incidence ratios (SIRs) of previously diagnosed comorbidities for hepatocellular carcinoma (HCC), gallbladder cancer (GBC), cholangiocarcinoma (CCA) and ampullary cancer. The 13 comorbidities included alcohol and nonalcohol related liver disease, chronic obstructive pulmonary disease, gallstone disease, viral and other kinds of hepatitis, infection of bile ducts, hepatic and other autoimmune diseases, obesity and diabetes. Patients were identified from the Swedish Inpatient Register from 1987 to 2018, and their cancers were followed from 1997 onwards. SIRs for HCC were 80 to 100 in men and women diagnosed with hepatitis C virus and they were also >10 in patients diagnosed with hepatitis B virus, other kind of hepatitis, hepatic autoimmune disease and nonalcohol related liver disease. Many of these risks, as well as alcohol related liver disease, were either specific to HCC or were shared with intrahepatic CCA. For GBC, CCA and ampullary cancer infection of bile ducts was the main risk factor. Gallstone disease, nonhepatic autoimmune diseases and diabetes were associated with all hepatobiliary cancers. The limitations of the study include inability to cover some rare risk factors and limited follow-up time. Many of the considered comorbidities are characterized by chronic inflammation and/or overt immune disturbance in autoimmune diseases. The results suggest that local chronic inflammation and a related immune disturbance is the carcinogenic trigger for all these cancers. 相似文献
2.
Kari Hemminki MD PhD Kristina Sundquist MD PhD Jan Sundquist MD PhD Asta Försti PhD Vaclav Liska MD PhD Akseli Hemminki MD PhD Xinjun Li MD PhD 《Cancer》2023,129(8):1227-1236
Background
Autoimmune diseases are associated with many cancers but there is a lack of population-based studies with different autoimmune diseases that have a long follow-up. This is also true of hepatobiliary cancers, which include hepatocellular cancer (HCC) and rarer entities of gallbladder cancer (GBC), intra- and extrahepatic cholangiocarcinoma (iCCA and eCCA), and ampullary cancer.Methods
Diagnostic data on 43 autoimmune diseases were collected from the Swedish Inpatient Register from 1987 to 2018, and cancer data were derived from the national cancer registry from 1997 onward. Relative risks were expressed as standardized incidence ratios (SIRs).Results
In a population of 13.6 million, 1.1 million autoimmune diseases were diagnosed and subsequent hepatobiliary cancer was diagnosed in 3191 patients (17.2% of cancers). SIRs for HCC were 2.73 (men) and 2.86 (women), 3.74/1.96 for iCCA, 2.65/1.37 for GBC, 2.38/1.64 for eCCA, and 1.80/1.85 for ampullary cancer. Significant associations between autoimmune disease and HCC were observed for 13 autoimmune diseases, with the highest risks being for autoimmune hepatitis (48.92/73.53, men/women) and primary biliary cirrhosis (38.03/54.48). GBC was increased after six autoimmune diseases, with high SIRs for ulcerative colitis (12.22/3.24) and men with Crohn disease (9.16). These autoimmune diseases were also associated with a high risk of iCCA, which had seven other associations, and eCCA, which had five other associations. Ampullary cancer occurrence was increased after four autoimmune diseases.Conclusion
An autoimmune disease is a common precursor condition for hepatobiliary cancers. This calls for careful control of autoimmune disease symptoms in each patient and encouragement to practice a healthy lifestyle. 相似文献3.
Subhayan Chattopadhyay Guoqiao Zheng Amit Sud Kristina Sundquist Jan Sundquist Asta Försti Richard Houlston Akseli Hemminki Kari Hemminki 《International journal of cancer. Journal international du cancer》2020,146(4):970-976
Second primary cancers (SPCs) account for an increasing proportion of all cancer diagnoses and family history of cancer may be a risk factor for SPCs. Using the Swedish Family-Cancer Database on non-Hodgkin lymphoma (NHL), we assessed the influence of family history on risk of SPCs and of SPCs on survival. NHL patients were identified from the years 1958 to 2015 and generalized Poisson models were used to calculate relative risks (RRs) for SPCs and familial SPCs. Among 14,393 NHL patients, a total of 1,866 (13.0%) were diagnosed with SPC. Familial risk of nine particular cancers was associated with risks of these cancers as SPCs, with twofold to fivefold increase in RRs. At the end of a 25-year follow-up period, the survival probability for persons with SPC was only 20% of that for patients without SPC; the hazard ratio for SPC was 1.59 (95% CI: 1.46–1.72). Survival could be predicted by the prognostic groups based on first cancers and HRs increase systematically with worse prognosis yielding a trend of p = 4.6 × 10−5. SPCs had deleterious consequences for survival in NHL patients. Family history was associated with increasing numbers of SPCs. Prevention of SPCs and their early detection is an important target in the overall strategy to improve survival in NHL patients. Counseling for avoidance of risk factors and targeted screening based on family history are feasible steps in risk reduction. 相似文献
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5.
Bleomycin‐induced chromosomal damage and shortening of telomeres in peripheral blood lymphocytes of incident cancer patients 下载免费PDF全文
Michal Kroupa Zdenka Polivkova Sivaramakrishna Rachakonda Michaela Schneiderova Sona Vodenkova Tomas Buchler Katerina Jiraskova Marketa Urbanova Ludmila Vodickova Kari Hemminki Rajiv Kumar Pavel Vodicka 《Genes, chromosomes & cancer》2018,57(2):61-69
Disruption of genomic integrity due to deficient DNA repair capacity and telomere shortening constitute hallmarks of malignant diseases. Incomplete or deficient repair of DNA double‐strand breaks (DSB) is manifested by chromosomal aberrations and their frequency reflects inter‐individual differences of response to exposure to mutagenic compounds. In this study, we investigated chromosomal integrity in peripheral blood lymphocytes (PBL) from newly diagnosed cancer patients, including 47 breast (BC) and 44 colorectal cancer (CRC) patients and 90 matched healthy controls. Mutagen sensitivity was evaluated by measuring chromatid breaks (CTAs) induced by bleomycin and supplemented by the chemiluminescent measurement of γ‐H2AX phosphorylation in 19 cancer patients (11 BC, 8 CRC). Relative telomere length (RTL) was determined in 22 BC, 32 CRC, and 64 controls. We observed statistically significant increased level of CTAs (P = .03) and increased percentage of aberrant cells (ACs) with CTAs (P = .05) in CRC patients compared with controls after bleomycin treatment. No differences were observed between BC cases and corresponding controls. CRC and BC patients with shorter RTL (below median) exhibited significantly higher amount of ACs (P = .02), CTAs (P = .02), and cells with high frequency of CTAs (≥12 CTAs/PBL; P = .03) after bleomycin treatment. No such associations were observed in healthy controls. γ‐H2AX phosphorylation after bleomycin treatment in PBL did not differ between CRC and BC patients. Our results suggest that altered DSB repair measured by sensitivity towards mutagen in PBL occurs particularly in CRC carcinogenesis. Irrespective of cancer type, telomere shortening may be associated with a decreased capacity to repair DSB. 相似文献
6.
7.
Xiangdong Liu Kari Hemminki Asta Försti Kristina Sundquist Jan Sundquist Jianguang Ji 《International journal of cancer. Journal international du cancer》2015,137(4):903-910
Epidemiological studies indicate that risks of certain cancers are increased in individuals hospitalized for type 2 diabetes mellitus (T2DM), which may not be representative of the entire population of T2DM patients as most of them are treated in primary health cares. To examine the subsequent cancer risk in individuals with T2DM from hospitals and primary health cares, and in their siblings and spouses, standardized incidence ratios (SIRs) were used to assess systematically risks of 35 cancer sites/types in individuals with T2DM using a nationwide Swedish database covering the period 1964 through 2010. Increased SIRs were recorded for 24 cancer sites/types in individuals with T2DM. The highest SIRs were for pancreatic cancer and liver cancer (2.98 and 2.43, respectively). A decreased SIR was noted for prostate cancer. Five cancers showed increased SIRs during the whole follow‐up period: colon, liver, pancreatic, endometrial and kidney cancers. T2DM patients in inpatient, outpatient and primary health care showed similar risk patterns. The overall SIRs for cancer in the siblings and spouses of individuals with T2DM were 0.97 and 1.01, respectively. The insulin users showed an overall increased risk of cancer. This study showed increased risks of 24 cancers in individuals with T2DM, but not in their siblings or spouses, suggesting that the profound metabolic disturbances of the underlying disease may explain the observed increases. Further studies examining the endogenous and exogenous factors underlying these associations are needed. 相似文献
8.
Yasmeen Niazi Hauke Thomsen Bozena Smolkova Ludmila Vodickova Sona Vodenkova Michal Kroupa Veronika Vymetalkova Alena Kazimirova Magdalena Barancokova Katarina Volkovova Marta Staruchova Per Hoffmann Markus M. Nöthen Maria Dušinská Ludovit Musak Pavel Vodicka Kari Hemminki Asta Försti 《Environmental and molecular mutagenesis》2019,60(1):17-28
Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10−5 in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. Environ. Mol. Mutagen. 60:17–28, 2019. © 2018 Wiley Periodicals, Inc. 相似文献
9.
Effective single chain antibody (scFv) concentrations in vivo via adenoviral vector mediated expression of secretory scFv 总被引:7,自引:0,他引:7
Arafat WO Gómez-Navarro J Buchsbaum DJ Xiang J Wang M Casado E Barker SD Mahasreshti PJ Haisma HJ Barnes MN Siegal GP Alvarez RD Hemminki A Nettelbeck DM Curiel DT 《Gene therapy》2002,9(4):256-262
Single chain antibodies (scFv) represent powerful interventional agents for the achievement of targeted therapeutics. The practical utility of these agents have been limited, however, by difficulties related to production of recombinant scFv and the achievement of effective and sustained levels of scFv in situ. To circumvent these limitations, we have developed an approach to express scFv in vivo. An anti-erbB2 scFv was engineered for secretion by eukaryotic cells. The secreted scFv could bind to its target and specifically suppress cell growth of erbB2-positive cells in vitro. Adenoviral vectors expressing the cDNA for the secretory scFv likewise could induce target cells to produce an anti-tumor anti-erbB2 scFv. In vivo gene transfer via the anti-erbB2 scFv encoding adenovirus also showed anti-tumor effects. Thus, by virtue of engineering a secreted version of the anti-tumor anti-erbB-2 scFv, and in vivo expression via adenoviral vector, effective concentrations of scFv were achieved. In vivo gene transfer clearly represents a powerful means to realize effective scFv-based approaches. This method will likely have applicability for a range of disorders amenable to targeted therapeutic approaches. 相似文献
10.
Kari Hemminki Xinjun Li Asta F?rsti Jan Sundquist Kristina Sundquist 《BMC public health》2012,12(1):1-7