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The most likely diagnosis for a 72-year-old man presenting with jaundice and significant weight loss is pancreatic cancer. Jaundice occurs when there is an obstruction of the bile ducts, which can happen when a tumor develops in the head of the pancreas. This obstruction leads to the accumulation of bilirubin in the bloodstream, resulting in jaundice.

Additionally, pancreatic cancer is known for causing significant weight loss, often due to a combination of factors, including loss of appetite, malabsorption, and the body’s increased metabolic demands in response to cancer. In older adults, the presentation of jaundice along with unexplained weight loss is particularly concerning for malignancies in the pancreas.

In contrast, while colon cancer, esophageal cancer, and gastric cancer can present with weight loss, they typically do not cause jaundice unless there is an advanced stage where liver involvement occurs. Pancreatic cancer stands out in this scenario, given the association of biliary obstruction and the typical age at diagnosis, making it the most fitting diagnosis in this case.