Abstract
AIM: Our aim was to examine two-way increased-risk associations between hepatobiliary cancers and malignancies that develop before/after them. PATIENTS AND METHODS: Data of USA from Surveillance, Epidemiology, and End Results (SEER), 17 registries (2000-2021) were analyzed using different statistical methods. RESULTS: Overall, 5,574,604 cancer cases were identified, which included hepatocellular carcinoma (HCC) (59,764), cancer of bile duct (including Ampulla of Vater) (22,735), cancer of gallbladder (10,155), and other malignancies (5,481,950). We found two-way increased-risk associations for the following eight cancer pairs: HCC-upper aerodigestive tract, HCC-esophagus, HCC-stomach, HCC-anus, HCC-bile duct, HCC-lung/bronchus, HCC-non-Hodgkin lymphoma, and bile duct-stomach. After HCC or bile duct cancer, the standardized incidence ratios (SIRs) (95% CI) of the corresponding second primary malignancies (SPMs) were 1.88 (1.61-2.18), 1.46 (1.07-1.96), 1.59 (1.25-2.00), 3.53 (2.31-5.18), 3.98 (3.15-4.97), 1.54 (1.41-1.69), 2.2 (1.92-2.52), and 2.30 (1.59-3.21), respectively. In reverse order (i.e. HCC or bile duct cancer as SPM), the SIRs (95% CI) were 1.48 (1.34-1.62), 1.43 (1.06-1.90), 1.49 (1.22-1.79), 1.76 (1.27-2.36), 1.62 (1.03-2.44), 1.39 (1.27-1.53), 1.31 (1.19-1.44), and 1.73 (1.31-2.24), respectively. CONCLUSION: The major shared etiologic factors for the identified cancer pairs were life-style (smoking, alcohol use, and excess body weight), chronic infections (hepatitis B and C viruses), and genetic risks.