A 52-year-old man from rural West Africa develops hepatocellular carcinoma. Sequencing of the tumor shows a characteristic missense mutation at codon 249 of the TP53 gene. Chronic dietary exposure to which agent is the established cause of this mutational signature?

• A Vinyl chloride
• B Arsenic
• C Nitrosamines
• D Aflatoxin B1 ✓

Explanation

Aflatoxin D1, produced by Aspergillus flavus contaminating stored grains and peanuts, forms DNA adducts that cause a G to T transversion at TP53 codon 249, a signature found in hepatocellular carcinoma in regions where aflatoxin exposure and hepatitis D overlap. Vinyl chloride causes hepatic angiosarcoma, arsenic is linked to squamous cell carcinoma of skin and lung, and nitrosamines are associated with gastric and esophageal cancers.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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