Factors for the development of gallbladder cancer in North Indians and an evaluation of specific proteins for the early detection

• Project/Area Number: 16K09080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Epidemiology and preventive medicine
• Research Institution: Hokuriku University
• Principal Investigator: Ikoma Toshikazu 北陸大学, 医療保健学部, 准教授 (60612744)
• Co-Investigator(Kenkyū-buntansha): 遠藤 和男 新潟医療福祉大学, 健康科学部, 教授 (60176790) ; 土屋 康雄 新潟大学, 医歯学総合研究科, 客員研究員 (60334679) ; 浅井 孝夫 新潟医療福祉大学, 医療技術学部, 講師 (60612736)
• Research Collaborator: Kapoor Vinay ; Mishra Kumudesh ; Behari Anu ; Shukla Pooja ; Vishwakarma Ruchira
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 胆嚢がん / インド / 環境要因 / 遺伝要因 / 特異蛋白質 / 特異蛋白 / 疫学成因解明研究 / 予防医学

Outline of Final Research Achievements

Our findings show that older age, low education level, low socioeconomic status, bowel habits once a day or less, non-vegetarian, access to tap water, use of well water, cooking with firewood are associated with increased risk of gallbladder cancer. Although our findings need confirmation whether incidence of gallbladder cancer would be reduced by preventing these factors, our data show that lack of vegetables and fruits intake and supply of unsafe drinking water are modifiable risk factors for the development of gallbladder cancer in north Indians.
We also found that the CC genotype of TP53 rs1042522 polymorphism is associated with an increased risk of gallbladder cancer. The GG genotype of the TP53 polymorphism was previously shown to have a more potent apoptosis-inducing activity than the CC genotype. Carriers with the CC genotype among North Indians appear to show an increased risk of developing gallbladder cancer, which may be due to the lower apoptosis-inducing activity.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果をもとに、インド胆嚢がんの発症メカニズムは、①非菜食主義による食物繊維の摂取不足がもたらす糞便の腸内停滞、②胆汁中の二次胆汁酸濃度の増加、③肝臓から胆汁へのコレステロール過剰分泌が誘導され、コレステロール胆石形成の促進、④腸チフス菌慢性感染によりコレステロール胆石表面にバイオフィルムを形成し、生体防御系から隠れて治療に対する抵抗性を獲得、⑤異形成や前がん病変への進行促進、⑥胆嚢がん発症、という過程が考えられた。もし、腸チフス菌が胆嚢がん発症の因果的役割を果たしていることが他の研究で証明されれば、その対策を講じることにより胆嚢がんは予防可能な疾患となりうると考えられる。

Research Products

• [Int'l Joint Research] サンジャイ ガンジー医科学大学院(インド)
• [Int'l Joint Research] サンジャイ・ガンジー医科学大学院(インド)
• [Int'l Joint Research] サンジャイ・ガンジー医科学大学院(インド)
• [Journal Article] Tumor protein p53 and K-ras gene mutations in Peruvian patients with gallbladder cancer (2019)
  • Author(s): Vidaurre T, Casavilca S, Montenegro P, Gomez H, Calderon M, Navarro J, Aramburu J, Poquioma E, Tsuchiya Y, Asai T, Ajioka Y, Sato A, Ikoma T, Nakamura K
  • Journal Title: Asian Pac J Cancer Prev Volume: 20 Issue: 1 Pages: 289-294
  • DOI: 10.31557/apjcp.2019.20.1.289
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Drinking water survey to elucidate risk factors in a region with high incidence of gallbladder cancer in India (2018)
  • Author(s): 生駒俊和, 浅井孝夫, 遠藤和男, 土屋康雄
  • Journal Title: Japanese Journal of Medical Technology Volume: 67 Issue: 5 Pages: 760-765
  • DOI: 10.14932/jamt.18-29
  • NAID: 130007500873
  • ISSN: 0915-8669, 2188-5346
  • Year and Date: 2018-10-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plasma Helicobacter pylori antibody titers and Helicobacter pylori infection positivity rates in patients with gallbladder cancer or cholelithiasis: a hospital-based case-control study (2018)
  • Author(s): Tsuchiya Y, Mishra K, Kapoor VK, Vishwakarma R, Behari A, Ikoma T, Asai T, Endoh K, Nakamura K.
  • Journal Title: Asian Pac J Cancer Prev Volume: 19 Pages: 1911-1915
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Lack of an Apparent Association between Mycotoxin Concentrations in Red Chili Peppers and Incidence of Gallbladder Cancer in India : an Ecological Study (2016)
  • Author(s): Ikoma T, Kapoor VK, Behari A, Mishra K, Tsuchiya Y, Asai T, Endoh K, Okano K, Nakamura K
  • Journal Title: Asian Pacific Journal of Cancer Prevention Volume: 17(7) Pages: 3499-3503
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Drinking water pollution and gallbladder cancer risk in northern India (2018)
  • Author(s): Ikoma T, Tsuchiya Y, Asai T, Endoh K, Puneet
  • Organizer: APCON 2018
  • Int'l Joint Research
• [Presentation] Polymorphism of DNA repair pathway gene and gallbladder cancer risk (2018)
  • Author(s): Tsuchiya Y, Mishra K, Behari A, Ikoma T, Kapoor VK
  • Organizer: APCON 2018
  • Int'l Joint Research