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Genetic Variations, Exposure to Persistent Organic Pollutants and Breast Cancer Risk – A Greenlandic Case–Control Study
Author(s) -
Wielsøe Maria,
Eiberg Hans,
Ghisari Mandana,
Kern Peder,
Lind Ole,
BonefeldJørgensen Eva Cecilie
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13002
Subject(s) - breast cancer , odds ratio , single nucleotide polymorphism , case control study , medicine , oncology , physiology , xenobiotic , confidence interval , cyp17a1 , cancer , genetics , biology , endocrinology , gene , genotype , biochemistry , enzyme
This study investigated the effects of single nucleotide polymorphisms ( SNP s) in xenobiotic and steroid hormone‐metabolizing genes in relation to breast cancer risk and explored possible effect modifications on persistent organic pollutants ( POP s) and breast cancer associations. The study also assessed effects of Greenlandic BRCA 1 founder mutations. Greenlandic Inuit women (77 cases and 84 controls) were included. We determined two founder mutations in BRCA 1 : Cys39Gly (rs80357164) and 4684del CC , and five SNP s in xenobiotic and oestrogen‐metabolizing genes: CYP 17A1 ‐34T>C (rs743572), CYP 19A1 *19C>T (rs10046), CYP 1A1 Ile462Val (rs1048943), CYP 1B Leu432Val (rs1056836) and COMT Val158Met (rs4680). We used chi‐square test for comparison of categorical variables between groups. Odds ratio ( OR ) estimates with 95% confidence interval (95% CI ) were obtained using logistic regression models. The variant allele of BRCA 1 Cys39Gly increased breast cancer risk (Gly/Cys versus Cys/Cys, OR : 12.2, 95% CI : 1.53; 98.1), and carriers of the variant allele of CYP 17A1 ‐34T>C had reduced risk ( CT + CC versus TT , OR : 0.44, 95% CI : 0.21; 0.93). CYP 17A1 ‐34T>C was an effect modifier on the association between perfluoroalkyl acids ( PFAA s) and breast cancer risk (∑ PFAA , ratio of OR : 0.18, 95% CI : 0.03; 0.97). Non‐significant modifying tendencies were seen for the other SNP s on the effect of polychlorinated biphenyls, organochlorine pesticides and PFAA s. In summary, the BRCA 1 Cys39Gly and CYP 17A1 ‐34T>C genetic variations were associated with breast cancer risk. Our results indicate that the evaluated genetic variants modify the effects of POP exposure on breast cancer risk; however, further studies are needed to document the data from the relatively small sample size.