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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

Författare och institution:
E. J. Duell (-); N. Travier (-); L. Lujan-Barroso (-); L. Dossus (-); M. C. Boutron-Ruault (-); F. Clavel-Chapelon (-); R. Tumino (-); G. Masala (-); V. Krogh (-); S. Panico (-); F. Ricceri (-); M. L. Redondo (-); M. Dorronsoro (-); E. Molina-Montes (-); J. M. Huerta (-); A. Barricarte (-); K. T. Khaw (-); N. J. Wareham (-); N. E. Allen (-); R. Travis (-); P. D. Siersema (-); P. H. M. Peeters (-); A. Trichopoulou (-); E. Fragogeorgi (-); E. Oikonomou (-); H. Boeing (-); M. Schuetze (-); F. Canzian (-); A. Lukanova (-); A. Tjønneland (-); N. Roswall (-); K. Overvad (-); E. Weiderpass (-); I. T. Gram (-); E. Lund (-); Björn Lindkvist (Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition); D. Johansen (-); W. Ye (-); M. Sund (-); V. Fedirko (-); M. Jenab (-); D. S. Michaud (-); E. Riboli (-); H. B. Bueno-de-Mesquita (-)
Publicerad i:
International Journal of Cancer, 132 ( 9 ) s. 2164-2175
Artikel, refereegranskad vetenskaplig
Sammanfattning (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. What's new Because the incidence of pancreatic cancer is 30-50% higher in men than women, researchers have wondered whether exposure to estrogen might offer a protective effect. The answer thus far has been unclear, however. In this study, the authors examined menstrual and reproductive factors in women, as well as exogenous hormone use. They also examined variants of the CYP17A1 gene in both women and men, as this gene is essential for sex-steroid metabolism. Only early age of menarche showed any association with pancreatic cancer risk. Copyright © 2012 UICC.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Cancer och onkologi
Klinisk medicin ->
Reproduktionsmedicin och gynekologi ->
Obstetrik och kvinnosjukdomar
CYP17A1, estrogens, hormones, menstruation, pancreatic cancer, reproduction, women, cytochrome P450 17, sex hormone, adult, aged, article, cancer incidence, cancer risk, cancer susceptibility, cohort analysis, controlled study, CYP17A1 gene, disease association, female, gene, gene locus, genetic variability, human, major clinical study, male, menarche, pancreas cancer, priority journal, prospective study, risk factor, single nucleotide polymorphism, steroid metabolism, Adenocarcinoma, Case-Control Studies, Follow-Up Studies, Genotype, Haplotypes, Humans, Middle Aged, Neoplasm Staging, Pancreatic Neoplasms, Polymorphism, Single Nucleotide, Prognosis, Prospective Studies, Reproductive History, Risk Factors, Steroid 17-alpha-Hydroxylase
Postens nummer:
Posten skapad:
2014-03-24 10:44
Posten ändrad:
2015-03-27 11:29

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