Cancer of unknown primary: searching for the etiological clues. A population-based epidemiological study in Sweden.

This thesis aimed to search for etiological clues about cancer of unknown primary(CUP) by gathering novel information. The Swedish national registries were used and CUP cases were identified according to the seventh revision of the International Classification of Diseases. A consistent increase before the late 1990s and a dramatic decrease afterwards were observed for CUP incidence among Swedes,regardless of sex. Comparable time trends were noted among Norwegians and Finns. CUP and lung cancer were the two most common causes of death. The familial SIR for CUP was 1.69 when a sibling was diagnosed with CUP. As to discordant associations, CUP was notably associated with lung, kidney, and colorectal cancers. A significantly increased SIR of 1.69 was observed among patients for the subsequent development of other cancers. An overall SIR of 0.88 was observed in immigrants compared with native Swedes. The decreased risks tended to be lower for women. In conclusion, causes of death may include lethal metastasis from the CUP or the recurrence of the hidden primary. The association of CUP with families of kidney, lung and colorectal cancers suggests a marked genetic basis and the sharing of metastatic mechanisms by many cancer types, which matches those coming up in tissue-of-origin determinations and, hence, proposes the missing origins. Different patterns of risk excess after CUP may be suggestive of possible roles for disease-and therapy-related immunosuppression, reappearance of hidden primary tumors, or genetic predisposition. The varied risks in immigrants indicate the environmental/genetic influence in early life on CUP development.