BACKGROUND: Second primary cancers (SPCs) are important clinically as they may negatively influence patient survival and they may tell about therapeutic side effects and general causes of cancer. Population-based literature concerning SPCs after hepatobiliary cancers is limited and here we assess risks of SPCs after hepatocellular cancer (HCC), and cancers of the gallbladder, bile ducts and ampulla of Vater. In reverse order, we consider the risk of hepatobiliary cancers as SPCs after any cancer. METHODS: We used standardized incidence ratios (SIRs) to estimate bidirectional relative risks of subsequent cancers associated with hepatobiliary cancers. Cancer diagnoses were obtained from the Swedish Cancer Registry from years 1990 through 2015. RESULTS: We identified 9997 primary HCCs, 1365 gallbladder cancers and 4721 bile duct cancers. After HCC, risks of four SPCs were increased: gallbladder (SIR = 4.38; 95% confidence interval 1.87-8.67), thyroid (4.13; 1.30-9.70), kidney (2.92; 1.66-4.47) and squamous cell skin (1.55; 1.02-2.26) cancers. In reverse order, HCC as SPC, in addition to the above cancers, associations included upper aerodigestive tract, esophageal, small intestinal and bladder cancers and non-Hodgkin lymphoma. For gallbladder and bile duct cancers, associations were found with small intestinal and pancreatic cancers. CONCLUSION: The results suggested that HCC is associated with two types of SPC, one related to shared environmental risk factors, such as alcohol, exemplified by upper aerodigestive tract and esophageal cancer, and the other related to immune dysfunction, exemplified by squamous cell skin cancer. SPCs associated with gallbladder and bile duct cancers suggest predisposition to mutations in the mismatch repair gene MLH1.

• Klíčová slova
• cancer etiology, cancer incidence, hepatobiliary cancer, relative risk, second primary cancer,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Most literature on second primary cancers (SPCs) focuses on possible factors, which may increase the risk of these cancers, and little attention has been paid for the overall incidence differences between first primary cancers (FPCs) and same SPCs. We wanted to compare the incidence rates for all common cancers when these were diagnosed as FPCs and SPCs after invasive and in situ squamous cell carcinoma (SCC) of the skin, which are usually treated by surgery only. METHODS: Cancers were identified from the Swedish Cancer Registry from the years 1990 through to 2015, and they included, in addition to skin cancers, 20 male cancers totaling 484,850 patients and 22 female cancers totaling 452,909 patients. Standardized incidence rates and relative risks (RRs) were calculated for sex-specific common cancers as FPC and as SPC after skin SCC. Spearman rank correlations were used in the analysis of incidence ranking of FPC and SPC. RESULTS: Of total, 29,061 men and 23,533 women developed invasive SCC and 27,842 men and 36,383 women in situ SCC. The total number of 20 other male cancers was 484,850 and of 22 female cancers it was 452,909. Rank correlations ranged from 0.90 to 0.96 (P~5×10-6), indicating that overall skin SCC did not interfere with SPC formation. The exceptions were increased SPC risks for melanoma, sharing risk factors with skin SCC, and non-Hodgkin and Hodgkin lymphoma, and cancers of the upper aerodigestive tract, connective tissue, and male and female genitals suggesting contribution by skin cancer initiated immune dysfunction. CONCLUSION: The incidence ranking of SPCs after skin cancers largely follows the incidence ranking of FPCs indicating that overall skin SCC does not greatly interfere with the intrinsic carcinogenic process. The main deviations in incidence between FPC and SPC appeared to be due to shared risk factors or immunological processes promoting immune responsive cancer types.

• Klíčová slova
• first primary cancer, immune disturbance, second cancer, skin cancer,
• Publikační typ
• časopisecké články MeSH