title: Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort.
abstract: Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (<12 vs. 13 years) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR = 1.44; 95% CI = 0.99-2.10). CYP17A1 rs619824 was associated with HRT use (p value = 0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort.
authors.affiliation: Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. eduell@iconcologia.net
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Duell
authors.forename: Noémie
authors.initials: N
authors.lastname: Travier
authors.forename: Leila
authors.initials: L
authors.lastname: Lujan-Barroso
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boutron-Ruault
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Giovanna
authors.initials: G
authors.lastname: Masala
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.forename: Fulvio
authors.initials: F
authors.lastname: Ricceri
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Redondo
authors.forename: Miren
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authors.lastname: Dorronsoro
authors.forename: Esther
authors.initials: E
authors.lastname: Molina-Montes
authors.forename: José M
authors.initials: JM
authors.lastname: Huerta
authors.forename: Aurelio
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authors.lastname: Barricarte
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: Naomi E
authors.initials: NE
authors.lastname: Allen
authors.forename: Ruth
authors.initials: R
authors.lastname: Travis
authors.forename: Peter D
authors.initials: PD
authors.lastname: Siersema
authors.forename: Petra H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Eirini
authors.initials: E
authors.lastname: Fragogeorgi
authors.forename: Eleni
authors.initials: E
authors.lastname: Oikonomou
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Madlen
authors.initials: M
authors.lastname: Schuetze
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Nina
authors.initials: N
authors.lastname: Roswall
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.forename: Inger Torhild
authors.initials: IT
authors.lastname: Gram
authors.forename: Eiliv
authors.initials: E
authors.lastname: Lund
authors.forename: Björn
authors.initials: B
authors.lastname: Lindkvist
authors.forename: Dorthe
authors.initials: D
authors.lastname: Johansen
authors.forename: Weimin
authors.initials: W
authors.lastname: Ye
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.forename: Veronika
authors.initials: V
authors.lastname: Fedirko
authors.forename: Mazda
authors.initials: M
authors.lastname: Jenab
authors.forename: Dominique S
authors.initials: DS
authors.lastname: Michaud
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: H Bas
authors.initials: HB
authors.lastname: Bueno-de-Mesquita
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008598:Menstruation; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000209:etiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D017584:Reproductive History; D012307:Risk Factors; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*
chemical_list: C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase