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

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kirurgi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Surgery (hsv//eng)

Nyckelord

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

pancreatic cancer

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)