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Hamidi Sofiani V, Ebrahimian Shiadeh A, Tabarraei A, Nikoo HR, Sadeghi F, Kamrani G, Yahyapour Y, Moradi A. Association of G12D mutation in the KRAS gene with HPV and EBV in gastrointestinal cancer tissues. J Int Med Res 2024; 52:3000605241302302. [PMID: 39673361 PMCID: PMC11645758 DOI: 10.1177/03000605241302302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 11/07/2024] [Indexed: 12/16/2024] Open
Abstract
OBJECTIVE This study aimed to explore the potential relationship between viral infections and gastrointestinal (GI) malignancies, focusing on the presence of KRAS G12D mutations. Specifically, we investigated the association of viral agents, including human papillomavirus (HPV) and Epstein-Barr virus (EBV), with KRAS G12D mutations in GI cancers to better understand their combined role in cancer development. METHODS This cross-sectional study comprised 92 patients diagnosed with GI cancer and 100 healthy individuals in the control group. All samples were examined to detect the KRAS G12D gene mutation and the existence of HPV and EBV using real-time polymerase chain reaction assays. RESULTS HPV and EBV DNA were detected in 5.4% and 51.4% of gastric cancer samples and in 7.3% and 49.1% of colorectal cancer samples, respectively. Analysis of KRAS G12D in plasma samples revealed heterozygous mutations in 54% of patients with gastric cancer and 35% of patients with colorectal tumors. Among EBV-positive colorectal cancer samples, 1.8% were wild-type, while 47.2% exhibited heterozygous mutations. Among HPV-positive colorectal cancer patients, 1.8% exhibited wild-type KRAS, 5.4% had heterozygous mutations, and 3.2% had homozygous mutations. CONCLUSION This study detected a significant correlation between the presence of viral agents and KRAS G12D mutations.
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Affiliation(s)
- Vahideh Hamidi Sofiani
- Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Arefeh Ebrahimian Shiadeh
- Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Alijan Tabarraei
- Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Hadi Razavi Nikoo
- Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Farzin Sadeghi
- Department of Medical Microbiology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Ghodsieh Kamrani
- Department of Pathology, School of Medicine, Faculty of Medicine and Clinical Research Development Center, Babol University of Medical Sciences, Babol, Iran
| | - Yousef Yahyapour
- Department of Medical Microbiology, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Abdolvahab Moradi
- Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
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Pan PH, Luo CW, Ting WC, Shiu BH, Huang JY, Tsai SCS, Lin FCF. Impact of Ascending HPV Infection on Colorectal Cancer Risk: Evidence from a Nationwide Study. Microorganisms 2024; 12:1746. [PMID: 39338421 PMCID: PMC11434182 DOI: 10.3390/microorganisms12091746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 08/16/2024] [Accepted: 08/20/2024] [Indexed: 09/30/2024] Open
Abstract
Colorectal cancer (CRC) is a prevalent and escalating health issue in Taiwan. This nationwide study delves into the relationship between Human Papillomavirus (HPV) infection and CRC risk, employing population datasets from 2007 to 2017. Cox regression analyses revealed a statistically significant hazard ratio (HR) of 1.73 (95% CI: 1.63-1.83) for CRC in HPV-positive patients, indicating a considerably elevated risk compared to non-infected individuals. Further, stratification by sex showed males with HPV have a higher CRC risk (HR = 1.49, 95% CI: 1.40-1.58) compared to females. Age-related analysis uncovered a progressive increase in CRC risk with advancing age (HR = 34.69 for over 80 years). The study of specific CRC subtypes showed varying risks: HR = 1.74 for the colon, HR = 1.64 for the rectum, and a notably higher HR = 4.72 for the anus. Comorbid conditions such as hypertension (HR = 1.26), diabetes mellitus (HR = 1.32), and abnormal liver function (HR = 1.18) also correlate with significantly increased CRC risks. These findings suggest that HPV is a significant risk factor for CRC, with disparities in risk based on anatomical location, demographic characteristics, and comorbidities, highlighting the need for intervention strategies and targeted prevention.
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Affiliation(s)
- Pin-Ho Pan
- Division of Pediatric Gastroenterology, Department of Pediatrics, Tungs' Taichung MetroHarbor Hospital, Taichung 43503, Taiwan
- Department of Post-Baccalaureate Medicine, National Chung Hsing University, Taichung 402202, Taiwan
| | - Ci-Wen Luo
- Department of Medical Research, Tungs' Taichung MetroHarbor Hospital, Taichung 43503, Taiwan
| | - Wen-Chien Ting
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Bei-Hao Shiu
- Division of Colorectal Surgery, Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Jing-Yang Huang
- Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Stella Chin-Shaw Tsai
- Department of Post-Baccalaureate Medicine, National Chung Hsing University, Taichung 402202, Taiwan
- Superintendent Office, Tungs' Taichung MetroHarbor Hospital, Taichung 43503, Taiwan
- College of Life Sciences, National Chung Hsing University, Taichung 402202, Taiwan
| | - Frank Cheau-Feng Lin
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
- Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
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Nagata M, Miyagi K, Hernandez BY, Kuwada SK. Multiethnic Trends in Early Onset Colorectal Cancer. Cancers (Basel) 2024; 16:398. [PMID: 38254887 PMCID: PMC10814620 DOI: 10.3390/cancers16020398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Revised: 01/09/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Current characteristics of early onset colorectal cancer (EOCRC) in the United States have been mainly studied in Whites, African Americans, and Hispanics, but little is known in regard to EOCRC in Asians and Native Hawaiians in the US. EOCRC was examined in Hawaii's multiethnic population. Data from the Hawaii Tumor Registry was used to analyze colorectal cancer (CRC) cases diagnosed in Hawaii from 2000-2019 by subsite, age, gender, ethnicity, and stage. Ethnicity analyses were limited to 3524 CRC cases, diagnosed between 2015-2019. Average annual 5-year age-adjusted incidence and mortality rates, average annual percent change over time, and 5-year survival were evaluated. Group comparisons utilized Chi-square and binomial proportion tests. Overall CRC incidence and mortality declined and were more pronounced for colon than rectal/rectosigmoid junction cancers. Colon cancer incidence rates significantly increased 1.46-fold for cases diagnosed under 45 years of age and rectal/rectosigmoid cancers significantly increased 1.54-fold for cases 45-54 years of age. CRC incidence increased sharply for females aged 45-54 years from 2000-2009 to 2010-2019, and increases in colon and rectal/rectosigmoid cancer among individuals aged 45-54 were higher for females. Among both sexes, the increase in rectal/rectosigmoid cancer incidence for individuals under 55 years was highest for stage I cancers. Overall, the mean (SD) age of CRC diagnosis was 5-10 years earlier for Native Hawaiians (60.6 [13.3] years) compared with Japanese, Chinese, Filipinos, Whites, and Other Asians (p < 0.001). Native Hawaiians constituted a greater proportion of CRC diagnosed under age 55 years and, conversely, a smaller proportion of cases 55 years and older compared with Japanese, Chinese, Filipinos, Whites, and Other Asians. Native Hawaiians had a significantly higher CRC-related mortality rate (14.5 per 100,000 [95% CI: 12.4, 16.8]) compared with Japanese (10.7 per 100,000 [95% CI: 9.3, 12.3]) and a significantly lower CRC survival rate (62.2% [95% CI: 59.1, 65.2]) compared with Japanese (71.9% [95% CI: 69.9, 73.8]), Filipinos (71.9% [95% CI: 69.2, 74.4]), Chinese (70.2% [95% CI: 65.5, 74.4]), Whites (69.3% [95% CI: 67.1, 71.4]), and Other Asians (71.7% [95% CI: 66.2, 76.5]). In our diverse US population, Native Hawaiians contribute disproportionately to EOCRC and present 5-10 years earlier than Whites, Japanese, Chinese, and Filipinos. EOCRCs are increasing faster in females than males in Hawaii, which differs from trends in the general US population. Emerging ethnic disparities in EOCRC in the US speak to the need for studies on targeted interventions and ethnic-specific risk factors for EOCRC.
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Affiliation(s)
- Michelle Nagata
- Population Sciences in the Pacific Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA; (K.M.); (B.Y.H.)
| | - Kohei Miyagi
- Population Sciences in the Pacific Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA; (K.M.); (B.Y.H.)
| | - Brenda Y. Hernandez
- Population Sciences in the Pacific Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA; (K.M.); (B.Y.H.)
| | - Scott K. Kuwada
- Cancer Biology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI 96813, USA;
- Department of Medicine, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI 96813, USA
- Gastroenterology, The Queen’s Medical Center, 550 South Beretania Street, Honolulu, HI 96813, USA
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Jian C, Jing Z, Yinhang W, Jinlong D, Yuefen P, Quan Q, Shuwen H. Colorectal cancer and gut viruses: a visualized analysis based on CiteSpace knowledge graph. Front Microbiol 2023; 14:1239818. [PMID: 37928670 PMCID: PMC10622771 DOI: 10.3389/fmicb.2023.1239818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 10/03/2023] [Indexed: 11/07/2023] Open
Abstract
Background Gut microbiome is a complex community of microbes present in the human gut and plays an important role in the occurrence and progression of colorectal cancer (CRC). However, the relationship between virus and CRC has not been fully understood. Objective To explore the hot spots and research trends in the field of CRC and virus. Methods By using the bibliometric analysis tool CiteSpace and based on the articles of the Web of Science Core Collection (WoSCC) database, the country, institution, highly cited literature, keywords and so on were visually analyzed. Results A total of 356 research articles on CRC from 2001 to 2023 were thoroughly analyzed. The USA and China have made the largest contribution in the field of virus and CRC. The Helmholtz Association published the most papers. There were relatively few cooperations among institutions from different countries. The results of keyword cluster analysis proved that the literature on the relationship between human cytomegalovirus (CMV) and CRC was the most widely studied aspect in this field. "Gut microbiota," "inflammatory bowel disease," "hepatitis b virus," and "human papillomavirus infection" are the current research hotspots; "oncolytic virus," "apoptosis," and "gut microbiome" are the recent research frontiers and should be paid closer attention. Conclusion By using CiteSpace bibliometric software, the visual analysis reflected the research trends and hot topics of virus and CRC. In addition, the prevalence and mechanism of specific virus on CRC were also reviewed, which provides valuable references for future CRC research.
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Affiliation(s)
- Chu Jian
- Fifth School of Clinical Medicine of Zhejiang Chinese Medical University (Huzhou Central Hospital), Huzhou, China
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer, Huzhou, China
| | - Zhuang Jing
- Fifth School of Clinical Medicine of Zhejiang Chinese Medical University (Huzhou Central Hospital), Huzhou, China
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer, Huzhou, China
| | - Wu Yinhang
- Fifth School of Clinical Medicine of Zhejiang Chinese Medical University (Huzhou Central Hospital), Huzhou, China
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer, Huzhou, China
| | - Duan Jinlong
- Huzhou Hospital of Traditional Chinese Medicine, Huzhou, China
| | - Pan Yuefen
- Fifth School of Clinical Medicine of Zhejiang Chinese Medical University (Huzhou Central Hospital), Huzhou, China
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer, Huzhou, China
| | - Qi Quan
- Fifth School of Clinical Medicine of Zhejiang Chinese Medical University (Huzhou Central Hospital), Huzhou, China
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer, Huzhou, China
| | - Han Shuwen
- Fifth School of Clinical Medicine of Zhejiang Chinese Medical University (Huzhou Central Hospital), Huzhou, China
- Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, China
- Key Laboratory of Multiomics Research and Clinical Transformation of Digestive Cancer, Huzhou, China
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Khan I, Harshithkumar R, More A, Mukherjee A. Human Papilloma Virus: An Unraveled Enigma of Universal Burden of Malignancies. Pathogens 2023; 12:pathogens12040564. [PMID: 37111450 PMCID: PMC10146077 DOI: 10.3390/pathogens12040564] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 03/28/2023] [Accepted: 04/04/2023] [Indexed: 04/29/2023] Open
Abstract
HPV, or Human Papilloma Virus, has been the primary causative agent of genital warts and cervical cancer worldwide. It is a sexually transmitted infection mainly affecting women of reproductive age group, also infecting men and high-risk group individuals globally, resulting in high mortality. In recent years, HPV has also been found to be the major culprit behind anogenital cancers in both gender and oropharyngeal and colorectal cancers. Few studies have reported the incidence of HPV in breast cancers as well. For a few decades, the burden of HPV-associated malignancies has been increasing at an alarming rate due to a lack of adequate awareness, famine vaccine coverage and hesitancy. The effectiveness of currently available vaccines has been limited to prophylactic efficacy and does not prevent malignancies associated with post-exposure persistent infection. This review focuses on the current burden of HPV-associated malignancies, their causes and strategies to combat the growing prevalence of the cancers. With the advent of new technologies associated with treatment pertaining to therapeutic interventions and employing effective vaccine coverage, the burden of this disease may be reduced in the population.
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Affiliation(s)
- Ishrat Khan
- Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, India
| | - R Harshithkumar
- Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, India
| | - Ashwini More
- Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, India
| | - Anupam Mukherjee
- Division of Virology, ICMR-National AIDS Research Institute, Pune 411026, India
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6
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Network analysis of long non-coding RNA expression profiles in common warts. Heliyon 2022; 8:e11790. [DOI: 10.1016/j.heliyon.2022.e11790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 04/15/2022] [Accepted: 11/14/2022] [Indexed: 11/20/2022] Open
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Hsu CH, Lin YJ, Chen YC, Liu IL, You SL, Hu JM, Lin TC, Chang PK, Chen CY, Chou YC, Sun CA. Human Papillomavirus and Risk of Colorectal Cancer: An Analysis of Nationwide Claims Data. Medicina (B Aires) 2022; 58:medicina58101461. [PMID: 36295621 PMCID: PMC9610003 DOI: 10.3390/medicina58101461] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 10/04/2022] [Accepted: 10/10/2022] [Indexed: 01/24/2023] Open
Abstract
Background and Objectives: Although human papillomavirus (HPV) is a major etiology of cervical and anogenital cancers, whether it is associated with colorectal carcinogenesis is yet undetermined. Materials and Methods: The longitudinal association of HPV infection with colorectal cancer (CRC) was evaluated using 2000-2013 data from a nationwide Taiwanese claims database. In this retrospective cohort study, 358 patients with primary HPV diagnoses (HPV-infected cohort) and 1432 patients without such a diagnosis (HPV-uninfected cohort) were recruited between 2000 and 2006. Both cohorts were followed up to identify CRC incidences from 2006 to 2013. Hazard ratios (HRs) and their 95% confidence intervals (CIs) derived from Cox proportional hazards models were used to estimate the association between HPV and CRC risk. Results: The HPV-infected cohort had a significantly higher cumulative incidence of CRC than the HPV-uninfected cohort. The presence of HPV was associated with an increased risk of CRC (adjusted HR, 1.63; 95% CI, 1.02-3.62). Furthermore, the significant HPV-CRC risk association was evident in both sexes. Conclusions: This population-based cohort study reveals longitudinal evidence that HPV is associated with an increased risk of CRC. Further studies are required to verify the role of HPV in colorectal carcinogenesis.
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Affiliation(s)
- Chih-Hsiung Hsu
- School of Public Health, National Defense Medical Center, Taipei City 114, Taiwan
| | - Yu-Jyun Lin
- School of Public Health, National Defense Medical Center, Taipei City 114, Taiwan
| | - Yong-Chen Chen
- Department of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
- Data Science Center, College of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
| | - I-Lan Liu
- School of Public Health, National Defense Medical Center, Taipei City 114, Taiwan
| | - San-Lin You
- Department of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
- Data Science Center, College of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
| | - Je-Ming Hu
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City 114, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114, Taiwan
| | - Tzu-Chiao Lin
- Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114, Taiwan
| | - Pi-Kai Chang
- Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City 114, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114, Taiwan
| | - Chao-Yang Chen
- Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114, Taiwan
| | - Yu-Ching Chou
- School of Public Health, National Defense Medical Center, Taipei City 114, Taiwan
- Correspondence: (Y.-C.C.); (C.-A.S.)
| | - Chien-An Sun
- Data Science Center, College of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
- Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
- Correspondence: (Y.-C.C.); (C.-A.S.)
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Cordeiro Silva AT, Santos N, Bezerra Tocantins P, Bernardes Leão-Cordeiro J, Ataides F, Rosa Marques LO. The human papillomavirus in colorectal cancer. JOURNAL OF MEDICAL SCIENCES 2022. [DOI: 10.4103/jmedsci.jmedsci_194_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Marongiu L, Allgayer H. Viruses in colorectal cancer. Mol Oncol 2021; 16:1423-1450. [PMID: 34514694 PMCID: PMC8978519 DOI: 10.1002/1878-0261.13100] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 07/15/2021] [Accepted: 09/10/2021] [Indexed: 12/23/2022] Open
Abstract
Increasing evidence suggests that microorganisms might represent at least highly interesting cofactors in colorectal cancer (CRC) oncogenesis and progression. Still, associated mechanisms, specifically in colonocytes and their microenvironmental interactions, are still poorly understood. Although, currently, at least seven viruses are being recognized as human carcinogens, only three of these – Epstein–Barr virus (EBV), human papillomavirus (HPV) and John Cunningham virus (JCV) – have been described, with varying levels of evidence, in CRC. In addition, cytomegalovirus (CMV) has been associated with CRC in some publications, albeit not being a fully acknowledged oncovirus. Moreover, recent microbiome studies set increasing grounds for new hypotheses on bacteriophages as interesting additional modulators in CRC carcinogenesis and progression. The present Review summarizes how particular groups of viruses, including bacteriophages, affect cells and the cellular and microbial microenvironment, thereby putatively contributing to foster CRC. This could be achieved, for example, by promoting several processes – such as DNA damage, chromosomal instability, or molecular aspects of cell proliferation, CRC progression and metastasis – not necessarily by direct infection of epithelial cells only, but also by interaction with the microenvironment of infected cells. In this context, there are striking common features of EBV, CMV, HPV and JCV that are able to promote oncogenesis, in terms of establishing latent infections and affecting p53‐/pRb‐driven, epithelial–mesenchymal transition (EMT)‐/EGFR‐associated and especially Wnt/β‐catenin‐driven pathways. We speculate that, at least in part, such viral impacts on particular pathways might be reflected in lasting (e.g. mutational or further genomic) fingerprints of viruses in cells. Also, the complex interplay between several species within the intestinal microbiome, involving a direct or indirect impact on colorectal and microenvironmental cells but also between, for example, phages and bacterial and viral pathogens, and further novel species certainly might, in part, explain ongoing difficulties to establish unequivocal monocausal links between specific viral infections and CRC.
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Affiliation(s)
- Luigi Marongiu
- Department of Experimental Surgery - Cancer Metastasis, Medical Faculty Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany
| | - Heike Allgayer
- Department of Experimental Surgery - Cancer Metastasis, Medical Faculty Mannheim, Ruprecht-Karls-University of Heidelberg, Mannheim, Germany
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PICANÇO-JUNIOR OM, THEODORO TR, ALBUQUERQUE PJDBS, PINHEIRO RN, WAISBERG J. PRESENÇA DO PAPILOMAVIRUS HUMANO TIPO 16 E EXPRESSÃO GÊNICA DA PROTEÍNA P16INK4A E ONCOPROTEÍNA E7 NO CARCINOMA COLORRETAL. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2021; 34:e1637. [PMID: 35107499 PMCID: PMC8846486 DOI: 10.1590/0102-672020210002e1637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 08/30/2021] [Indexed: 12/24/2022]
Abstract
Human papillomavirus (HPV) is the agent of the most prevalent sexually
transmitted diseases in the world associated with cervix and anal canal cancer.
The action of HPV on colorectal carcinogenesis is not yet established.
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11
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Prevalence of human papilloma virus and Epstein–Barr virus in tumorous and adjacent tissues of colorectal cancer in Iran. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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12
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Dalla Libera LS, de Siqueira T, Santos IL, Porto Ramos JE, Milhomen AX, de Alencar RDCG, Rabelo Santos SH, dos Santos Carneiro MA, Figueiredo Alves RR, Saddi VA. Detection of Human papillomavirus and the role of p16INK4a in colorectal carcinomas. PLoS One 2020; 15:e0235065. [PMID: 32584870 PMCID: PMC7316293 DOI: 10.1371/journal.pone.0235065] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 06/08/2020] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION Human papillomavirus (HPV) infection is associated with the development of anogenital and head and neck cancers. In recent years a potential role of HPV in colorectal cancer (CRC) has been suggested. OBJECTIVE To investigate the presence of HPV in colorectal carcinomas and to study the role of p16INK4a as a marker of transcriptionally active HPV infection. In addition, to investigate the correlation between these findings and the CRC prognostic factors. METHODS Case control study with 92 cases of colorectal cancers, 75 controls of normal tissue adjacent to the tumor, and 30 controls of precursor lesions, including polyps and colorectal adenomas. Paraffinized samples were used, HPV detection and genotyping were performed by PCR and reverse hybridization by using the INNO LIPA kit, with SPF10 plus primers. The expression of the p16INK4a protein was investigated using immunohistochemistry. Data analysis was performed using descriptive, univariate statistics and survival curves were calculated by using the Kaplan Meier and log-rank method. RESULTS HPV was detected in 13% of the cases and the most prevalent genotype was HPV 16. HPV DNA was not detected in either control groups. The high expression of p16INK4a was observed in 30% of the cases, but it was not associated to the presence of HPV. The overall survival was 53.3% and was influenced by prognostic factors such as later stage, lymph node and distant metastasis. CONCLUSIONS Based on these results, HPV is unlikely to be involved in colorectal carcinogenesis and p16INK4a expression is not a relevant marker of transcriptionally active HPV infection in CRC.
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Affiliation(s)
- Larisse Silva Dalla Libera
- Universidade Federal de Goiás (UFG), Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Faculdade de Medicina (FM) e Instituto de Patologia Tropical e Saúde Pública (IPTSP), Goiânia, GO, Brasil
| | - Thalita de Siqueira
- Pontifícia Universidade Católica de Goiás (PUC/GO), Programa de Pós-Graduação em Ciências Ambientais e Saúde (MCAS) e Escola de Ciências Médicas, Farmacêuticas e Biomédicas (ECMFB), Goiânia, GO, Brasil
| | - Igor Lopes Santos
- Pontifícia Universidade Católica de Goiás (PUC/GO), Programa de Pós-Graduação em Ciências Ambientais e Saúde (MCAS) e Escola de Ciências Médicas, Farmacêuticas e Biomédicas (ECMFB), Goiânia, GO, Brasil
| | - Jéssica Enocencio Porto Ramos
- Pontifícia Universidade Católica de Goiás (PUC/GO), Programa de Pós-Graduação em Ciências Ambientais e Saúde (MCAS) e Escola de Ciências Médicas, Farmacêuticas e Biomédicas (ECMFB), Goiânia, GO, Brasil
| | - Amanda Xavier Milhomen
- Pontifícia Universidade Católica de Goiás (PUC/GO), Programa de Pós-Graduação em Ciências Ambientais e Saúde (MCAS) e Escola de Ciências Médicas, Farmacêuticas e Biomédicas (ECMFB), Goiânia, GO, Brasil
| | | | - Silvia Helena Rabelo Santos
- Universidade Federal de Goiás (UFG), Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Faculdade de Medicina (FM) e Instituto de Patologia Tropical e Saúde Pública (IPTSP), Goiânia, GO, Brasil
| | - Megmar Aparecida dos Santos Carneiro
- Universidade Federal de Goiás (UFG), Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Faculdade de Medicina (FM) e Instituto de Patologia Tropical e Saúde Pública (IPTSP), Goiânia, GO, Brasil
| | - Rosane Ribeiro Figueiredo Alves
- Universidade Federal de Goiás (UFG), Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Faculdade de Medicina (FM) e Instituto de Patologia Tropical e Saúde Pública (IPTSP), Goiânia, GO, Brasil
| | - Vera Aparecida Saddi
- Universidade Federal de Goiás (UFG), Programa de Pós-Graduação em Ciências da Saúde (PPGCS), Faculdade de Medicina (FM) e Instituto de Patologia Tropical e Saúde Pública (IPTSP), Goiânia, GO, Brasil
- Pontifícia Universidade Católica de Goiás (PUC/GO), Programa de Pós-Graduação em Ciências Ambientais e Saúde (MCAS) e Escola de Ciências Médicas, Farmacêuticas e Biomédicas (ECMFB), Goiânia, GO, Brasil
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13
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Malki MI, Gupta I, Fernandes Q, Aboulkassim T, Yasmeen A, Vranic S, Al Moustafa AE, Al-Thawadi HA. Co-presence of Epstein-Barr virus and high-risk human papillomaviruses in Syrian colorectal cancer samples. Hum Vaccin Immunother 2020; 16:2403-2407. [PMID: 32186955 DOI: 10.1080/21645515.2020.1726680] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
We recently performed two studies exploring the presence of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs) types 16, 18, 31, 33 and 35 in human colorectal cancers from the Syrian population. Herein, we report that EBV and high-risk HPVs are co-present in colorectal cancers from Syria. We reveal that 17 (~17%) of 102 cancer samples are positive for both EBV and high-risk HPVs and their co-presence is associated with high/intermediate grade invasive carcinomas. These data suggest that EBV and high-risk HPVs are co-present in human colorectal cancers where they might cooperate on the initiation and/or progression of these cancers. Thus, we believe that future studies are necessary to confirm the co-presence of these oncoviruses and their cooperative role in human colorectal carcinogenesis.
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Affiliation(s)
| | - Ishita Gupta
- College of Medicine, QU Health, Qatar University , Doha, Qatar.,Biomedical Research Centre, Qatar University , Doha, Qatar
| | - Queenie Fernandes
- College of Medicine, QU Health, Qatar University , Doha, Qatar.,Biomedical Research Centre, Qatar University , Doha, Qatar
| | - Tahar Aboulkassim
- Segal Cancer Centre, Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital , Montreal, Quebec, Canada
| | - Amber Yasmeen
- Segal Cancer Centre, Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital , Montreal, Quebec, Canada
| | - Semir Vranic
- College of Medicine, QU Health, Qatar University , Doha, Qatar
| | - Ala-Eddin Al Moustafa
- College of Medicine, QU Health, Qatar University , Doha, Qatar.,Biomedical Research Centre, Qatar University , Doha, Qatar
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14
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Martins SF, Mariano V, Rodrigues M, Longatto-Filho A. Human papillomavirus (HPV) 16 infection is not detected in rectal carcinoma. Infect Agent Cancer 2020; 15:17. [PMID: 32165915 PMCID: PMC7059378 DOI: 10.1186/s13027-020-00281-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Accepted: 02/19/2020] [Indexed: 12/18/2022] Open
Abstract
Introduction Persistence of human papillomavirus (HPV) infections is associated with squamous cell carcinomas of different human anatomic sites. Several studies have suggested a potential role for HPV infection, particularly HPV16 genotype, in rectal cancer carcinogenesis.. The aim of this study was to assess the frequency of oncogenic HPV 16 viral DNA sequences in rectal carcinomas cases retrieved from the pathology archive of Braga Hospital, North Portuga. Methods TaqMan-based type-specific real-time PCR for HPV 16 was performed using primers and probe targeting HPV16 E7 region. Results Most of the rectal cancer patients (88.5%, n = 206 patients), were symptomatic at diagnosis. The majority of the lesions (55.3%, n = 129) presented malignancies of polypoid/vegetant phenotype. 26.8% (n = 63) had synchronic metastasis at diagnosis. 26.2% (n = 61) patients had clinical indication for neoadjuvant therapy. Most patients with rectal cancer were stage IV (19.7% patients), followed by stage IIA (19.3%) and stage I (18.5%). All cases of the present series tested negative for HPV16. Conclusion The total of negative tests for HPV 16 infection is a robust argument to support the assumption that HPV 16 infection, despite of previous evidences, is not involved in rectal cancer carcinogenesis and progression.
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Affiliation(s)
- Sandra F Martins
- 1Life and Health Science Research Institute (ICVS), School of Health Sciences, School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Braga, Portugal.,Coloproctology Unit, Braga Hospital, Braga, Portugal
| | - Vânia Mariano
- Molecular Oncology Research Center, Barretos, São Paulo, Brazil
| | | | - Adhemar Longatto-Filho
- 1Life and Health Science Research Institute (ICVS), School of Health Sciences, School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Braga, Portugal.,Molecular Oncology Research Center, Barretos, São Paulo, Brazil.,5Laboratory of Medical Investigation (LIM) 14, Faculty of Medicine, University of Sao Paulo, Sao Paulo, Brazil
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15
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Mjelle R, Sjursen W, Thommesen L, Sætrom P, Hofsli E. Small RNA expression from viruses, bacteria and human miRNAs in colon cancer tissue and its association with microsatellite instability and tumor location. BMC Cancer 2019; 19:161. [PMID: 30786859 PMCID: PMC6381638 DOI: 10.1186/s12885-019-5330-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 01/29/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND MicroRNAs (miRNA) and other small RNAs are frequently dysregulated in cancer and are promising biomarkers for colon cancer. Here we profile human, virus and bacteria small RNAs in normal and tumor tissue from early stage colon cancer and correlate the expression with clinical parameters. METHODS Small RNAs from colon cancer tissue and adjacent normal mucosa of 48 patients were sequenced using Illumina high-throughput sequencing. Clinical parameters were correlated with the small RNA expression data using linear models. We performed a meta-analysis by comparing publicly available small RNA sequencing datasets with our original sequencing data to confirm the main findings. RESULTS We identified 331 differentially expressed miRNAs between tumor and normal samples. We found that the major changes in miRNA expression between left and right colon are due to miRNAs located within the Hox-developmental genes, including miR-10b, miR-196b and miR-615. Further, we identified new miRNAs associated with microsatellite instability (MSI), including miR-335, miR-26 and miR-625. We performed a meta-analysis on all publicly available miRNA-seq datasets and identified 117 common miRNAs that were differentially expressed between tumor and normal tissue. The miRNAs miR-135b and miR-31 were the most significant upregulated miRNA in tumor across all datasets. The miRNA miR-133a was the most strongly downregulated miRNA in our dataset and also showed consistent downregulation in the other datasets. The miRNAs associated with MSI and tumor location in our data showed similar changes in the other datasets. Finally, we show that small RNAs from Epstein-Barr virus and Fusobacterium nucleatum are differentially expressed between tumor and normal adjacent tissue. CONCLUSIONS Small RNA profiling in colon cancer tissue revealed novel RNAs associated with MSI and tumor location. We show that Fusobacterium nucleatum are detectable at the RNA-level in colon tissue, and that both Fusobacterium nucleatum and Epstein-Barr virus separate tumor and normal tissue.
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Affiliation(s)
- Robin Mjelle
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Erling Skjalgssons gt 1, 7030, Trondheim, Norway.
| | - Wenche Sjursen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Erling Skjalgssons gt 1, 7030, Trondheim, Norway.,Department of Medical Genetics, St Olavs Hospital, Trondheim Norway, Erling Skjalgssons gt 1, 7030, Trondheim, Norway
| | - Liv Thommesen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Erling Skjalgssons gt 1, 7030, Trondheim, Norway.,Department of Biomedical Laboratory Science, Norwegian University of Science and Technology, NTNU, 7491, Trondheim, Norway
| | - Pål Sætrom
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Erling Skjalgssons gt 1, 7030, Trondheim, Norway.,Department of Computer and Information Science, Norwegian University of Science and Technology, NTNU, Sem Sælandsvei 9, 7491, Trondheim, Norway.,Bioinformatics core facility-BioCore, Norwegian University of Science and Technology, NTNU, 7491, Trondheim, Norway.,K.G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, NTNU, 7491, Trondheim, Norway
| | - Eva Hofsli
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Erling Skjalgssons gt 1, 7030, Trondheim, Norway.,The Cancer Clinic, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
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16
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Mirzaei H, Goudarzi H, Eslami G, Faghihloo E. Role of viruses in gastrointestinal cancer. J Cell Physiol 2017; 233:4000-4014. [PMID: 28926109 DOI: 10.1002/jcp.26194] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 09/08/2017] [Indexed: 12/22/2022]
Abstract
Gastrointestinal cancers are a global public health problem, which represent a vast majority of all cancer-caused deaths in both men and women. On the other hand, viral pathogens have been long implicated as etiological factors in the onset of certain human cancers, including gastrointestinal tumors. In this regard, Human Papilloma Virus (HPV), Epstein-Barr Virus (EBV), and John Cunningham Virus (JCV) have been more strongly suggested to be involved in gastrointestinal carcinogenesis; so that, the association of HPV with oropharyngeal and anal cancers and also the association of EBV with gastric cancer have been etiologically confirmed by epidemiological and experimental investigations. Although, the association of other viruses is less evident, but may rely on co-factors for their oncogenic roles. Therefore, to improve the prevention and treatment of these classes of cancer, their association with viral agents as potential risk factors should be investigated with care. In this respect, the present review has focused on the existing literature on the subject of viral involvement in gastrointestinal tumorgenesis, by covering and discussing various gastrointestinal cancers, corresponding viral agents and their oncogenic aspects and then summarizing evidences either supporting or rejecting a causal role of these pathogens in gastrointestinal malignancies.
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Affiliation(s)
- Habibollah Mirzaei
- Department of Virology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hossein Goudarzi
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gita Eslami
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ebrahim Faghihloo
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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17
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Bucchi D, Stracci F, Buonora N, Masanotti G. Human papillomavirus and gastrointestinal cancer: A review. World J Gastroenterol 2016; 22:7415-7430. [PMID: 27672265 PMCID: PMC5011658 DOI: 10.3748/wjg.v22.i33.7415] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 06/29/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention.
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18
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High Prevalence of Human Papillomavirus in Colorectal Cancer in Hispanics: A Case-Control Study. Gastroenterol Res Pract 2016; 2016:7896716. [PMID: 26904111 PMCID: PMC4745930 DOI: 10.1155/2016/7896716] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 10/11/2015] [Indexed: 01/16/2023] Open
Abstract
The role of Human Papillomavirus (HPV) in colorectal carcinogenesis remains elusive. Based on the high incidence of HPV-associated malignancies among Puerto Rican Hispanics, this study aimed to assess the prevalence of HPV infection and viral integration in colorectal tissues in order to evaluate its putative role in colorectal cancer (CRC). In this case-control study, the prevalence of HPV infection in CRC (cases n = 45) and normal colon mucosa from cancer-free subjects (controls n = 36) was assessed by a nested PCR strategy. HPV-16 genotyping was performed in HPV-positive tissues and the physical status of the HPV-16 genome was determined by E2 detection. HPV was detected in 19 of 45 (42.2%) CRC cases (mean age 61.1 ± 10.7 years, 24 males) and in 1 of 36 (2.8%) controls (mean age 60.9 ± 9.6 years, 24 males) with an OR = 25.58 (95% CI 3.21 to 203.49). HPV-16 was detected in 63.2% of the HPV-positive colorectal tumors; genome integration was observed in all HPV-16 positive cases. This is the first report showing the high prevalence of HPV infections in Caribbean Hispanic colorectal tumors. Despite evidence of HPV integration into the host genome, further mechanistic analysis examining HPV oncoprotein expression and the putative role of these oncoproteins in colorectal carcinogenesis is warranted.
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19
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Chen H, Chen XZ, Waterboer T, Castro FA, Brenner H. Viral infections and colorectal cancer: a systematic review of epidemiological studies. Int J Cancer 2015; 137:12-24. [PMID: 25186851 DOI: 10.1002/ijc.29180] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2014] [Revised: 07/30/2014] [Accepted: 08/26/2014] [Indexed: 12/25/2022]
Abstract
Numerous studies have found the presence of viral DNA in colorectal tumor tissues. However, whether viral infections contribute to the risk of colorectal cancer (CRC) is still under debate. We aimed to provide an overview of published epidemiological studies on the association between viral infections and CRC. A systematic literature search was performed in PubMed to find relevant studies published until 8 May 2014. Information collected included study population, sample type, laboratory method and prevalence of viral infection in cancer or precancer patients and controls. We found 41 studies that fulfilled the selection criteria, all of which had cross-sectional or case-control designs, and most of which were of small to moderate size. Viral infections included human papillomaviruses (HPV), human polyomaviruses, human herpesviruses, human bocavirus and Inoue-Melnick virus. Inconsistent results were observed across studies. Many studies reported higher viral DNA prevalence in tumor tissues than in normal noncancerous tissues either in the same patients or in CRC-free controls. However, potential contamination or temporal sequence of the infection and cancer development were often unclear. Seroprevalence studies assessing antibody titers indicative of viral infections did not find statistically significant differences between CRC cases and healthy controls. Overall published evidence on the role of viral infections in CRC etiology remains limited. Given the potential importance of viral infections and their implication for prevention, there is a strong need for large, methodologically rigorous epidemiological studies.
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Affiliation(s)
- Hongda Chen
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
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20
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Downregulation of external death receptor genes FAS and DR5 in colorectal cancer samples positive for human papillomavirus infection. Pathol Res Pract 2015; 211:444-8. [DOI: 10.1016/j.prp.2015.02.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 02/05/2015] [Accepted: 02/05/2015] [Indexed: 01/07/2023]
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21
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Lorenzon L, Mazzetta F, Pilozzi E, Uggeri G, Torrisi MR, Ferri M, Ziparo V, French D. Human papillomavirus does not have a causal role in colorectal carcinogenesis. World J Gastroenterol 2015; 21:342-350. [PMID: 25574110 PMCID: PMC4284354 DOI: 10.3748/wjg.v21.i1.342] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2014] [Revised: 06/24/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the presence of human papillomavirus (HPV) DNA along with the integration, the quantification and the expression of the HPV16 in colorectal cancers.
METHODS: A prospective series of colorectal tumors were genotyped for HPV DNA. The clinical and pathological variables of the HPV-positive tumors were compared to those of HPV-negative samples. The integration status of HPV16 was evaluated by calculating E2/E6 ng ratios. HPV16-positive tumors were also evaluated for (1) E2, E4, E5, E6 and E7 viral gene ng quantification; (2) relative quantification compared to W12 cells; and (3) viral E2, E4, E5, E6 and E7 mRNA transcripts by real-time polymerase chain reaction.
RESULTS: HPV infection was detected in 16.9% of all tumors examined, and HPV16 was the most frequent type detected (63.6% of positive tissues). Notably, the clinical and pathological features of HPV-positive colorectal cancers were not significantly different than those of HPV-negative cancers (χ2 and t-test for all clinical and pathological features of HPV-positive vs HPV-negative colorectal cancers: p ns). HPV16 DNA was present exclusively in episomal form, and the HPV16 E2, E4, E5, E6 and E7 genes were detected in trace nanogram quantities. Furthermore, the HPV16 genes ranged from 10-3 to 10-9 compared to W12 cells at an episomal stage. Although the extractions were validated by housekeeping gene expression, all the HPV16 positive tissues were transcriptionally inactive for the E2, E4, E5, E6 and E7 mRNAs.
CONCLUSION: Based on our results, HPV is unlikely involved in colorectal carcinogenesis.
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22
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Involvement of potassium channels in the progression of cancer to a more malignant phenotype. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2014; 1848:2477-92. [PMID: 25517985 DOI: 10.1016/j.bbamem.2014.12.008] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Revised: 12/01/2014] [Accepted: 12/08/2014] [Indexed: 12/22/2022]
Abstract
Potassium channels are a diverse group of pore-forming transmembrane proteins that selectively facilitate potassium flow through an electrochemical gradient. They participate in the control of the membrane potential and cell excitability in addition to different cell functions such as cell volume regulation, proliferation, cell migration, angiogenesis as well as apoptosis. Because these physiological processes are essential for the correct cell function, K+ channels have been associated with a growing number of diseases including cancer. In fact, different K+ channel families such as the voltage-gated K+ channels, the ether à-go-go K+ channels, the two pore domain K+ channels and the Ca2+-activated K+ channels have been associated to tumor biology. Potassium channels have a role in neoplastic cell-cycle progression and their expression has been found abnormal in many types of tumors and cancer cells. In addition, the expression and activity of specific K+ channels have shown a significant correlation with the tumor malignancy grade. The aim of this overview is to summarize published data on K+ channels that exhibit oncogenic properties and have been linked to a more malignant cancer phenotype. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.
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23
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Tanzi E, Bianchi S, Frati ER, Amicizia D, Martinelli M, Bragazzi NL, Brisigotti MP, Colzani D, Fasoli E, Zehender G, Panatto D, Gasparini R. Human papillomavirus detection in paraffin-embedded colorectal cancer tissues. J Gen Virol 2014; 96:206-209. [PMID: 25296558 DOI: 10.1099/vir.0.070672-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.
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Affiliation(s)
- Elisabetta Tanzi
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Silvia Bianchi
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Elena R Frati
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Daniela Amicizia
- Department of Health Sciences, University of Genoa, Genoa, Italy
| | - Marianna Martinelli
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | | | - Maria Pia Brisigotti
- Pathological Anatomy and Histology Unit, IRCCS AOU San Martino-IST, Genoa, Italy
| | - Daniela Colzani
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Ester Fasoli
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Gianguglielmo Zehender
- Department of Biomedical and Clinical Sciences 'L. Sacco', University of Milan, Milan, Italy
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Jalilvand S, Shoja Z, Hamkar R. Human Papillomavirus Burden in Different Cancers in Iran: a Systematic Assessment. Asian Pac J Cancer Prev 2014; 15:7029-35. [DOI: 10.7314/apjcp.2014.15.17.7029] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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25
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Engels EA, Wacholder S, Katki HA, Chaturvedi AK. Tumor-based case-control studies of infection and cancer: muddling the when and where of molecular epidemiology. Cancer Epidemiol Biomarkers Prev 2014; 23:1959-64. [PMID: 25063520 DOI: 10.1158/1055-9965.epi-14-0282] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
We describe the "tumor-based case-control" study as a type of epidemiologic study used to evaluate associations between infectious agents and cancer. These studies assess exposure using diseased tissues from affected individuals (i.e., evaluating tumor tissue for cancer cases), but they must utilize nondiseased tissues to assess control subjects, who do not have the disease of interest. This approach can lead to exposure misclassification in two ways. First, concerning the "when" of exposure assessment, retrospective assessment of tissues may not accurately measure exposure at the key earlier time point (i.e., during the etiologic window). Second, concerning the "where" of exposure assessment, use of different tissues in cases and controls can have different accuracy for detecting the exposure (i.e., differential exposure misclassification). We present an example concerning the association of human papillomavirus with various cancers, where tumor-based case-control studies likely overestimate risk associated with infection. In another example, we illustrate how tumor-based case-control studies of Helicobacter pylori and gastric cancer underestimate risk. Tumor-based case-control studies can demonstrate infection within tumor cells, providing qualitative information about disease etiology. However, measures of association calculated in tumor-based case-control studies are prone to over- or underestimating the relationship between infections and subsequent cancer risk.
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Affiliation(s)
- Eric A Engels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
| | - Sholom Wacholder
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Hormuzd A Katki
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
| | - Anil K Chaturvedi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland
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27
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Baandrup L, Thomsen LT, Olesen TB, Andersen KK, Norrild B, Kjaer SK. The prevalence of human papillomavirus in colorectal adenomas and adenocarcinomas: a systematic review and meta-analysis. Eur J Cancer 2014; 50:1446-61. [PMID: 24560489 DOI: 10.1016/j.ejca.2014.01.019] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Revised: 01/20/2014] [Accepted: 01/25/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association. METHODS The pooled HPV prevalence was estimated using a random effects model and the I(2) statistic was used to describe the amount of heterogeneity. Potential sources of heterogeneity were evaluated by meta-regression and stratified analyses. For the studies on adenocarcinomas including control tissue, random effects estimates of odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS Thirty-seven studies were included. Among the 2630 adenocarcinomas, the pooled HPV prevalence was 11.2% (95% CI, 4.9-19.6%) with substantial between-study heterogeneity (I(2)=97.2%). The HPV prevalence varied by geographical region with highest prevalence in South America (45.1%, 95% CI, 21.9-69.4%), Asia (39.2%, 95% CI, 20.3-60.0%) and the Middle East (32.2%, 95% CI, 1.1-79.3%), and by detection method with the highest HPV prevalence in PCR-based studies. In the eight case-control studies, the pooled HPV prevalence was 36.8% (95% CI, 21.3-53.8%) in adenocarcinomas and 1.6% (95% CI, 0.0-9.6%) in controls giving an OR of 6.0 (95% CI, 2.0-17.9%) for the association between HPV and colorectal cancer. Among the 415 adenomas, the pooled HPV prevalence was 5.1% (95% CI, 0.0-17.8%; I(2)=93.7%). CONCLUSIONS HPV may be associated with a subset of colorectal cancers. Future large-scale multicenter case-control studies with data on risk factors such as lifestyle and sexual behaviour are needed.
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Affiliation(s)
- Louise Baandrup
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark
| | - Louise T Thomsen
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark
| | - Tina Bech Olesen
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark
| | - Klaus Kaae Andersen
- Unit of Statistics, Bioinformatics and Registry, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark
| | - Bodil Norrild
- Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark
| | - Susanne K Kjaer
- Unit of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Strandboulevarden 49, 2100 Copenhagen, Denmark; Gynaecologic Clinic, Juliane Marie Center, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark.
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Damin DC, Ziegelmann PK, Damin AP. Human papillomavirus infection and colorectal cancer risk: a meta-analysis. Colorectal Dis 2013; 15:e420-8. [PMID: 23895733 DOI: 10.1111/codi.12257] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2012] [Accepted: 12/21/2012] [Indexed: 12/12/2022]
Abstract
AIM Human papillomavirus (HPV) infection is associated with cervical cancer, but whether it is involved in colorectal carcinogenesis is controversial. We conducted a meta-analysis to evaluate the association between HPV and colorectal adenocarcinoma. METHOD A search of the MEDLINE database was performed using the MESH terms 'HPV', 'human papillomavirus', and 'colon cancer', 'rectal cancer', 'colorectal cancer'. The prevalence of HPV infection in colorectal cancer was estimated by pooling data from 16 studies (involving 1436 patients) published up to July 2012, taking into consideration methodological heterogeneity between studies. The association of HPV with colorectal cancer risk was estimated from case-control studies. RESULTS The HPV overall prevalence was 31.9% (95% CI: 19.3-47.9). It was lowest in Europe (14.1%, 95% CI: 4.9-34.1) and highest in South America (60.8%, 95% CI: 42.7-76.4). Eight studies presented the results of HPV typing in 302 HPV-positive colorectal carcinomas. HPV 18 was the virus more frequently found in colorectal cancer cases from Asia (73.34%, 95% CI: 44.9-90.7) and Europe (47.3%, 95% CI: 34.5-60.4). In contrast, HPV 16 was more prevalent in colorectal tumours from South America (58.3%, 95% CI: 45.5-69.9). The analysis of five case-control studies showed an increase in colorectal carcinoma risk with HPV positivity (OR = 10.04; 95% CI: 3.7-27.5). CONCLUSION The results provide quantitative evidence for an association between HPV infection and colorectal cancer risk.
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Affiliation(s)
- D C Damin
- Department of Surgery, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
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Burnett-Hartman AN, Feng Q, Popov V, Kalidindi A, Newcomb PA. Human papillomavirus DNA is rarely detected in colorectal carcinomas and not associated with microsatellite instability: the Seattle colon cancer family registry. Cancer Epidemiol Biomarkers Prev 2012; 22:317-9. [PMID: 23250932 DOI: 10.1158/1055-9965.epi-12-1170] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Persistent infection with oncogenic human papillomavirus (HPV) types-16 and -18 is an established cause of cervical and other cancers. Some studies report detection of oncogenic HPV DNA in colorectal carcinomas, with prevalence estimates as high as 84%. However, other studies report detecting no HPV DNA in colorectal tumors. METHODS To evaluate the prevalence of HPV in colorectal cancer subsets, we conducted a case-case comparison study. This study included 555 cases of incident colorectal cancer from the Seattle Colon Cancer Family Registry (CCFR), ages 20 to 74 years and diagnosed between 1998 and 2002. Standardized interviews were used to elicit demographics and risk factor data. Tumor DNA was assayed for HPV-16 and -18 DNA using real-time PCR. Microsatellite instability (MSI) status was assessed using a standard 10-marker panel and confirmed with immunohistochemical staining. Prevalence estimates were calculated for the overall sample, and stratified by patient and tumor characteristics. Fisher exact test was used to compare prevalence between strata. RESULTS HPV-16 DNA was detected in 2% of colorectal tumors, but no HPV-18 DNA was detected. HPV-16 prevalence did not vary between cases according to sex, age, race, smoking-status, or MSI-status (P > 0.05). HPV-16 prevalence in rectal carcinomas was 5% compared with 1% in colon carcinomas (P = 0.03). CONCLUSIONS Among a large sample of colorectal carcinomas, prevalence of HPV-16 and -18 was very low. Prior studies detecting high HPV prevalence in colorectal carcinomas are likely the result of contamination from the anal canal or clinical processing. IMPACT HPV is unlikely to play a large role in colorectal carcinogenesis.
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Owens G, Martin-Hirsch P, Gajjar K. Persistent severe dysplasia of colonic neovagina: a case report. Eur J Obstet Gynecol Reprod Biol 2012; 166:111-2. [PMID: 23072927 DOI: 10.1016/j.ejogrb.2012.09.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Revised: 08/12/2012] [Accepted: 09/19/2012] [Indexed: 11/29/2022]
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Burnett-Hartman AN, Newcomb PA, Schwartz SM, Bostick RM, Pawlita M, Waterboer T, Potter JD. No association between antibodies to sexually transmitted infections and colorectal hyperplastic polyps in men: Minnesota Cancer Prevention Research Unit Polyp Study. Cancer Epidemiol Biomarkers Prev 2012; 21:1599-601. [PMID: 22736792 DOI: 10.1158/1055-9965.epi-12-0651] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Oncogenic human papillomaviruses (HPV) are sexually transmitted and linked to several epithelial malignancies, but an association between HPV and colorectal neoplasia is not established. Previously, we reported a three-fold increase in the odds of colorectal hyperplastic polyps associated with oncogenic HPV seropositivity in men but detected no HPV DNA in colorectal tissues from these same men. METHODS To test the reproducibility of our prior HPV antibody results and to explore the hypothesis that colorectal hyperplastic polyps may be associated with sexual behavior in men, we conducted a case-control study of hyperplastic polyps and antibodies to eight oncogenic HPV types (including 16 and 18), Herpes simplex virus-2 (HSV-2), and hepatitis C virus (HCV). Study participants were men, ages 30-74 years, enrolled in the Minnesota Cancer Prevention Research Unit Polyp Study who had an index colonoscopy from 1991 to 1994, and received a diagnosis of hyperplastic polyps (n = 97) or were polyp-free (n = 184). Plasma was assessed for antibodies to the eight oncogenic HPV types, HSV-2, and HCV using a bead-based multiplex assay. RESULTS The adjusted ORs for the association between hyperplastic polyps and seropositivity to oncogenic HPV (all eight types combined) was 0.84 [95% confidence interval (CI), 0.44-1.58; for HSV-2, OR, 0.98, 95% CI, 0.48-1.99; and for HCV, OR, 0.61; 95% CI, 0.11-3.26]. CONCLUSIONS Our study suggested no association between colorectal hyperplastic polyps and antibodies to specific sexually transmitted infections (STI) in men. IMPACT Factors associated with STIs are unlikely to play a role in the etiology of colorectal hyperplastic polyps in men.
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Blomberg M, Friis S, Munk C, Bautz A, Kjaer SK. Genital warts and risk of cancer: a Danish study of nearly 50 000 patients with genital warts. J Infect Dis 2012; 205:1544-53. [PMID: 22427679 DOI: 10.1093/infdis/jis228] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND We conducted a large national cohort study to examine the risk of cancer among men and women with genital warts (GW). METHODS By use of the Danish National Patient Register, we identified 16,155 men and 32,933 women who received a diagnosis of GW during 1978-2008. Standardized incidence ratios (SIRs) were computed as estimates of the relative risk of specific cancers or sites. RESULTS A diagnosis of GW was strongly related to anal (SIR for men, 21.5; SIR for women, 7.8), vulvar (SIR, 14.8), vaginal (SIR, 5.9), cervical (SIR, 1.5), penile (SIR, 8.2), and head and neck cancer (SIR, 2.8), including subsites of head and neck cancer with confirmed HPV association (SIR for men, 3.5; SIR for women, 4.8). The risks remained elevated for >10 years following GW diagnosis. In addition, we found moderately increased SIR estimates for nonmelanoma skin cancer, smoking-related cancers, and Hodgkin and non-Hodgkin lymphoma. CONCLUSIONS Individuals with GW have a long-term increased risk of anogenital cancers and head and neck cancers. The elevated risks of nonmelanoma skin cancers might indicate an association with HPV, while excess risks of other cancers could point to differences in other risk factors between individuals with GW and the general population.
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Affiliation(s)
- Maria Blomberg
- Institute of Cancer Epidemiology, Danish Cancer Society, Denmark
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zur Hausen H. Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer. Int J Cancer 2012; 130:2475-83. [PMID: 22212999 DOI: 10.1002/ijc.27413] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2011] [Accepted: 12/09/2011] [Indexed: 12/13/2022]
Abstract
An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections.
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Affiliation(s)
- Harald zur Hausen
- Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
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