TY - JOUR
T1 - 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
AU - Ghisari, Mandana
AU - Eiberg, Hans
AU - Long, Manhai
AU - Bonefeld-Jørgensen, Eva Cecilie
PY - 2014
Y1 - 2014
N2 - 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 χ2 –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 CYP1B1and 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.
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 χ2 –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 CYP1B1and 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.
KW - Breast cancer, Inuit, Genetic polymorphism, CYP1A1, CYP1B1, COMT, CYP19
M3 - Journal article
SN - 1476-069X
VL - 13
SP - 19
JO - Environmental Health: A Global Access Science Source
JF - Environmental Health: A Global Access Science Source
IS - 19
ER -