title: Merkel cell carcinoma and multiple primary cancers.
abstract: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin for which causative factors remain largely unknown. The site-specific risks of multiple primary cancers associated with MCC, which may provide insight into etiologic influences, have not been quantified in large population-based studies. We estimated the long-term risk of subsequent primary tumors after a first primary MCC (1,306 patients) and the risk of second primary MCC following other first primary cancers (2,048,739 patients) within 11 population-based cancer registries which report to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (1986-2002). Patients with first primary MCC were at significantly increased risk of developing a subsequent cancer [standardized incidence ratio (SIR), 1.22; 95% confidence intervals (95% CI), 1.01-1.45; observed (O = 122)], with significant excesses restricted to the first year after diagnosis (SIR, 1.71; 95% CI, 1.21-2.33; O = 39). Significantly elevated site-specific risks were observed for cancers of salivary gland (SIR, 11.55; 95% CI, 2.32-33.76; O = 3), biliary sites other than liver and gallbladder (SIR, 7.24; 95% CI, 1.46-21.16; O = 3), and non-Hodgkin lymphoma (SIR, 2.56; 95% CI, 1.23-4.71; O = 10). Nonsignificantly increased risks of 2-fold or higher were seen for chronic lymphocytic leukemia, and cancers of the small intestine and brain. A significantly increased 1.36-fold risk (95% CI, 1.19-1.55; O = 221) of MCC as a second primary malignancy was observed among patients with all other first primary cancers taken together. In particular, significant 3- to 7-fold excesses of MCC followed multiple myeloma (SIR, 3.70; 95% CI, 1.01-9.47; O = 4), chronic lymphocytic leukemia (SIR, 6.89; 95% CI, 3.77-11.57; O = 14), non-Hodgkin lymphoma (SIR, 3.37; 95% CI, 1.93-5.47; O = 16), and malignant melanoma (SIR, 3.05; 95% CI, 1.74-4.95; O = 16). Although enhanced medical surveillance may play a role, increased reciprocal risks suggest that MCC may share etiologic influences with other malignancies. Heightened awareness of the associations of lymphohematopoietic malignancies with MCC may facilitate early clinical recognition.
authors.affiliation: Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD 20892-7238, USA. reganho@mail.nih.gov
authors.forename: Regan A
authors.initials: RA
authors.lastname: Howard
authors.forename: Graça M
authors.initials: GM
authors.lastname: Dores
authors.forename: Rochelle E
authors.initials: RE
authors.lastname: Curtis
authors.forename: William F
authors.initials: WF
authors.lastname: Anderson
authors.forename: Lois B
authors.initials: LB
authors.lastname: Travis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015266:Carcinoma, Merkel Cell / Q000175:diagnosis*; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000209:etiology*; D012042:Registries; D018426:SEER Program; D012878:Skin Neoplasms / Q000175:diagnosis*