Lack of significant associations between single nucleotide polymorphisms in LPAL2-LPA genetic region and all cancer incidence and mortality in Japanese population: The Japan public health center-based prospective study |
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| Institution: | 1. Department of Medical Informatics, Center for Information, Jichi Medical University, Shimotsuke 329-0498, Japan;2. Health Data Science Research Section, Healthy Aging Innovation Center, Tokyo Metropolitan Geriatric Research Institute, Tokyo 173-0015, Japan;3. Biostatistics Division, Center for Research Administration and Support/Division of Biostatistical Research, Institute for Cancer Control, National Cancer Center, Tokyo 104-0045, Japan;4. Graduate School of Health Innovation, Kanagawa University of Human Services, Kanagawa, 210-0821, Japan;5. Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan;6. Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo 162-8480, Japan;7. Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan;8. Division of Prevention, National Cancer Center Institute for Cancer Control, Tokyo 104-0045, Japan;9. National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo 162-8636, Japan;10. Department of Molecular Pathology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Tokyo 113-8519, Japan;1. Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran;2. Biostatistics Research Group, Department of Health Science, University of Leicester, Leicester, UK;3. Patient Safety Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran;4. Cancer Research Center, Cancer Registry Section, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran;5. Shiraz Cancer Registry, Shiraz University of Medical Sciences, Shiraz, Iran;6. Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;7. HIV/STI Surveillance Research Center, and WHO collaborating Center for HIV, Institute for Futures studies in Health, Kerman Cancer Registry, Kerman University of Medical Sciences, Kerman, Iran;8. Kermanshah Cancer Registry, Kermanshah University of Medical Sciences, Kermanshah, Iran;9. Mazandaran Cancer Registry, Mazandaran University of Medical Sciences, Sari, Iran;10. Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, N. Kargar St, Tehran, Iran;11. Esfahan Cancer Registry, Esfahan University of Medical Sciences, Esfahan, Iran;12. Pathology and Stem Cell Research Center, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;13. Deputy of Health, Ministry of Health and Medical Education, Tehran, Iran;14. Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, USA;15. International Agency for Research on Cancer (IARC/WHO), Genomic Epidemiology Branch, Lyon, France;p. Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran;q. Department of Radiation Oncology, Imam Hossein Hospital, Shaheed Beheshti Medical University, Tehran, Iran;r. Iranian National Population-Based Cancer Registry Secretariat, Cancer Office, Deputy of Health, Ministry of Health, Tehran, Iran;s. Department of Epidemiology and Biostatistics, Kermanshah University of Medical Sciences, Kermanshah, Iran;t. Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran;1. Brown School, Washington University in St. Louis, St. Louis, MO, USA;2. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA;3. Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA;4. Rollins School of Public Health, Emory University, Atlanta, GA, USA;1. Department of Internal Medicine, Jackson Memorial Hospital / University of Miami Health System, FL, USA;2. The Population Registry of Cancer of the Metropolitan Area of Bucaramanga, Universidad Autónoma de Bucaramanga, Colombia;3. Department of Clinical Epidemiology and Biostatistics, Pontificia Universidad Javeriana, Bogota, Colombia;4. University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, FL, USA;1. Clinical Oncology Department, Faculty of Medicine, Assiut University, Assiut, Egypt;2. Clinical Pathology Department, Faculty of Medicine, Assiut University, Assiut, Egypt;1. Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N. Martin Ave., Tucson, AZ 85724, USA;2. Department of Community, Environment and Policy, Mel and Enid Zuckerman College of Public Health, University of Arizona, 1295 N. Martin Ave., Tucson, AZ 85724, USA;1. Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA;2. Division of Oncology, Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, PA, USA;3. Department of Genetics, University of Pennsylvania, Philadelphia, PA, USA;4. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA |
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| Abstract: | BackgroundHigh lipoprotein (a) level is an established cardiovascular risk, but its association with non-cardiovascular diseases, especially cancer, is controversial. Serum lipoprotein (a) levels vary widely by genetic backgrounds and are largely determined by the genetic variations of apolipoprotein (a) gene, LPA. In this study, we investigate the association between SNPs in LPA region and cancer incidence and mortality in Japanese.MethodsA genetic cohort study was conducted utilizing the data from 9923 participants in the Japan Public Health Center-based Prospective Study (JPHC Study). Twenty-five SNPs in the LPAL2-LPA region were selected from the genome-wide genotyped data. Cox regression analysis adjusted for the covariates and competing risks of death from other causes, were used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of overall and site-specific cancer incidence and mortality, for each SNP.ResultsNo significant association was found between SNPs in the LPAL2-LPA region and cancer incidence or mortality (overall/site-specific cancer). In men, however, HRs for stomach cancer incidence of 18SNPs were estimated higher than 1.5 (e.g., 2.15 for rs13202636, model free, 95%CI: 1.28–3.62) and those for stomach cancer mortality of 2SNPs (rs9365171, rs1367211) were estimated 2.13 (recessive, 95%CI:1.04–4.37) and 1.61 (additive, 95%CI: 1.00–2.59). Additionally, the minor allele for SNP rs3798220 showed increased death risk from colorectal cancer (CRC) in men (HR: 3.29, 95% CI:1.59 – 6.81) and decreased CRC incidence risk in women (HR: 0.46, 95%CI: 0.22–0.94). Minor allele carrier of any of 4SNPs could have risk of prostate cancer incidence (e.g., rs9365171 dominant, HR: 1.71, 95%CI: 1.06–2.77).ConclusionsNone of the 25 SNPs in the LPAL2-LPA region was found to be significantly associated with cancer incidence or mortality. Considering the possible association between SNPs in LPAL2-LPA region and colorectal, prostate and stomach cancer incidence or mortality, further analysis using different cohorts is warranted. |
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| Keywords: | Lipoprotein (a) LPAL2 LPA Cancer incidence Cancer mortality |
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