PMID- 24629213
OWN - NLM
STAT- MEDLINE
DCOM- 20141009
LR  - 20221207
IS  - 1476-069X (Electronic)
IS  - 1476-069X (Linking)
VI  - 13
IP  - 1
DP  - 2014 Mar 16
TI  - Polymorphisms in phase I and phase II genes and breast cancer risk and relations 
      to persistent organic pollutant exposure: a case-control study in Inuit women.
PG  - 19
LID - 10.1186/1476-069X-13-19 [doi]
AB  - BACKGROUND: We have previously reported that chemicals belonging to the 
      persistent organic pollutants (POPs) such as perfluorinated compounds (PFAS) and 
      polychlorinated biphenyls (PCBs) are risk factors in Breast Cancer (BC) 
      development in Greenlandic Inuit women. The present case-control study aimed to 
      investigate the main effect of polymorphisms in genes involved in xenobiotic 
      metabolism and estrogen biosynthesis, CYP1A1, CYP1B1, COMT and CYP17, CYP19 and 
      the BRCA1 founder mutation in relation to BC risk and to explore possible 
      interactions between the gene polymorphisms and serum POP levels on BC risk in 
      Greenlandic Inuit women. METHODS: The study population consisted of 31 BC cases 
      and 115 matched controls, with information on serum levels of POPs. Genotyping 
      was conducted for CYP1A1 (Ile462Val; rs1048943), CYP1B1 (Leu432Val; rs1056836), 
      COMT (Val158Met; rs4680), CYP17A1 (A1> A2; rs743572); CYP19A1 (C> T; rs10046) and 
      CYP19A1 ((TTTA)n repeats) polymorphisms and BRCA1 founder mutation using TaqMan 
      allelic discrimination method and polymerase chain reaction based restriction 
      fragment length polymorphism. The chi2 -test was used to compare categorical 
      variables between cases and controls and the odds ratios were estimated by 
      unconditional logistic regression models. RESULTS: We found an independent 
      association of CYP1A1 (Val) and CYP17 (A1) with BC risk.Furthermore, an increased 
      BC risk was observed for women with high serum levels of perfluorooctane 
      sulfonate (PFOS) and perfluorooctanoic acid (PFOA) and carriers of at least: one 
      CYP1A1 variant Val allele; one variant COMT Met allele; or the common CYP17 A1 
      allele. No combined effects were seen between PFAS exposure and CYP1B1 and CYP19 
      polymorphisms. The risk of BC was not found significantly associated with 
      exposure to PCBs and OCPs, regardless of genotype for all investigated SNPs. The 
      frequency of the Greenlandic founder mutation in BRCA1 was as expected higher in 
      cases than in controls. CONCLUSIONS: The BRCA1 founder mutation and polymorphisms 
      in CYP1A1 (Val) and CYP17 (A1) can increase the BC risk among Inuit women and the 
      risk increases with higher serum levels of PFOS and PFOA. Serum PFAS levels were 
      a consistent risk factor of BC, but inter-individual polymorphic differences 
      might cause variations in sensitivity to the PFAS/POP exposure.
FAU - Ghisari, Mandana
AU  - Ghisari M
FAU - Eiberg, Hans
AU  - Eiberg H
FAU - Long, Manhai
AU  - Long M
FAU - Bonefeld-Jorgensen, Eva C
AU  - Bonefeld-Jorgensen EC
AD  - Centre for Arctic Health & Unit of Cellular and Molecular Toxicology, Department 
      of Public Health, Aarhus University, Bartholins Alle 2, Build 1260, 8000 Aarhus 
      C, Denmark. ebj@mil.au.dk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140316
PL  - England
TA  - Environ Health
JT  - Environmental health : a global access science source
JID - 101147645
RN  - 0 (Alkanesulfonic Acids)
RN  - 0 (BRCA1 Protein)
RN  - 0 (BRCA1 protein, human)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Estrogens)
RN  - 0 (Fluorocarbons)
RN  - 0 (Xenobiotics)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 2.1.1.6 (COMT protein, human)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alkanesulfonic Acids/*blood
MH  - BRCA1 Protein/*genetics
MH  - Breast Neoplasms/*blood/epidemiology/*genetics
MH  - Case-Control Studies
MH  - Catechol O-Methyltransferase/genetics
MH  - Cytochrome P-450 Enzyme System/*genetics
MH  - Environmental Monitoring
MH  - Environmental Pollutants/*blood
MH  - Estrogens/metabolism
MH  - Female
MH  - Fluorocarbons/*blood
MH  - Greenland/epidemiology
MH  - Humans
MH  - Inuit/genetics
MH  - Middle Aged
MH  - Polychlorinated Biphenyls/blood
MH  - Polymorphism, Single Nucleotide
MH  - Risk
MH  - Xenobiotics/blood
MH  - Young Adult
PMC - PMC4234380
EDAT- 2014/03/19 06:00
MHDA- 2014/10/10 06:00
PMCR- 2014/03/16
CRDT- 2014/03/18 06:00
PHST- 2013/10/08 00:00 [received]
PHST- 2014/03/04 00:00 [accepted]
PHST- 2014/03/18 06:00 [entrez]
PHST- 2014/03/19 06:00 [pubmed]
PHST- 2014/10/10 06:00 [medline]
PHST- 2014/03/16 00:00 [pmc-release]
AID - 1476-069X-13-19 [pii]
AID - 10.1186/1476-069X-13-19 [doi]
PST - epublish
SO  - Environ Health. 2014 Mar 16;13(1):19. doi: 10.1186/1476-069X-13-19.