Pathology/B/14

Viral and microbial oncogenesis

ウイルス・微生物による発がん（腫瘍形成）

タグ: Mechanism / 機序High-yield / ポイント

1. Overview

Oncogenic microbes cause ~15–20% of cancers by inserting/expressing transforming genes, and often by driving chronic inflammation, regeneration, and ROS-mediated DNA damage. A single infection is usually insufficient — additional mutations are needed.

2. Oncogenic RNA virus

HTLV-1 (retrovirus; spread sexually, parenterally, breastfeeding): TAX gene inhibits p53 and drives polyclonal T-cell proliferation → secondary mutations → adult T-cell leukemia/lymphoma.

3. Oncogenic DNA viruses

Virus	Mechanism	Cancers
HPV (high-risk 16, 18, 31, 33)	E6 → degrades p53 (+Bax); E7 → inhibits Rb → releases E2F; inactivates CDK inhibitors	Cervical, anogenital, laryngeal carcinoma (low-risk 1,2,4,6/11 → warts)
EBV	Infects B cells (CD21); LMP-1 mimics CD40 → NF-κB/JAK-STAT; activates BCL2; EBNA-2 → cyclin D; viral IL-10	Burkitt (t(8;14)), Hodgkin, nasopharyngeal carcinoma, PTLD
HBV / HCV	Chronic hepatitis → injury, regeneration, ROS; HBx / HCV core activate signaling + block apoptosis (NF-κB)	Hepatocellular carcinoma

4. Microbial (bacterial) oncogenesis

Helicobacter pylori:
- Gastric adenocarcinoma: chronic gastritis → atrophy → intestinal metaplasia → dysplasia → carcinoma (CagA contributes).
- MALT lymphoma: antigenic stimulation → T-cell-driven B-cell proliferation → B-cell tumor (can regress after eradication).

💡 High-yield: HPV E6→p53, E7→Rb (cervical). EBV LMP-1→NF-κB (Burkitt t(8;14), nasopharyngeal). HBV/HCV → HCC via chronic inflammation. HTLV-1 TAX → adult T-cell leukemia. H. pylori → gastric adenocarcinoma (metaplasia-dysplasia) + MALT lymphoma (regresses with eradication).