title: Risk factors for cancers of unknown primary site: Results from the prospective EPIC cohort.
abstract: Cancer of unknown primary site (CUP) may be called an "orphan" disease, as it is diagnosed when metastases are detected while the primary tumor typically remains undetected, and because little research has been done on its primary causes. So far, few epidemiological studies, if any, have addressed possible risk factors for CUP. We analyzed data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (N=476,940). During prospective follow-up, a total of 651 cases of incident cases of CUP were detected (ICD-O-2 code C809). Proportional hazards models were conducted to examine the associations of lifetime history of smoking habits, alcohol consumption, levels of education and anthropometric indices of adiposity with risk of being diagnosed with CUP. Risk of being diagnosed with CUP was strongly related to smoking, with a relative risk of 3.66 [95% C.I., 2.24-5.97] for current, heavy smokers (26+ cigarettes/day) compared to never smokers (adjusted for alcohol consumption, body mass index, waist circumference and level of education) and a relative risk of 5.12 [3.09-8.47] for cases with CUP who died within 12 months. For alcohol consumption and level of education, weaker associations were observed but attenuated and no longer statistically significant after adjusting for smoking and indices of obesity. Finally, risk of CUP was increased by approximately 30 per cent for subjects in the highest versus lowest quartiles of waist circumference. Our analyses provide further documentation, in addition to autopsy studies, that a substantial proportion of cancers of unknown primary site may have their origin in smoking-related tumors, in particular.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Disorn
authors.initials: D
authors.lastname: Sookthai
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Alwin
authors.initials: A
authors.lastname: Krämer
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Elisabet
authors.initials: E
authors.lastname: Wirfält
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.forename: H B
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Valeria
authors.initials: V
authors.lastname: Pala
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.forename: Eva
authors.initials: E
authors.lastname: Ardanaz
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: Nerea
authors.initials: N
authors.lastname: Larrañaga
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Göran
authors.initials: G
authors.lastname: Hallmans
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000453:epidemiology / Q000209:etiology*; D009752:Nutritional Status; D009765:Obesity / Q000150:complications*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D055105:Waist Circumference; D049629:Waist-Hip Ratio; D055815:Young Adult
keywords: alcohol; cancer of unknown primary site (CUP); obesity; prospective cohort study; smoking; waist circumference