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3860243 
Journal Article 
Polymorphism in xenobiotic and estrogen metabolizing genes, exposure to perfluorinated compounds and subsequent breast cancer risk: A nested case-control study in the Danish National Birth Cohort 
Ghisari, M; Long, M; Røge, DM; Olsen, J; Bonefeld-Jørgensen, EC 
2017 
Yes 
Environmental Research
ISSN: 0013-9351
EISSN: 1096-0953 
154 
325-333 
English 
In the present case-cohort study based on prospective data from Danish women, we aimed to estimate the main effect of polymorphisms in genes known to be involved in the steroid hormone metabolic pathway and xenobiotic metabolism on the risk of developing breast cancer. We also studied a possible effect measure modification between genotypes and levels of serum perfluoroalkylated substances (PFASs) on the risk to breast cancer. We have previously reported a weak association between serum PFASs levels and the risk of breast cancer for this study population of Danish pregnant nulliparous women as well as in a smaller case-control study of Greenlandic women. The study population consisted of 178 breast cancer cases and 233 controls (tabnulliparous and frequency matched on age) nested within the Danish National Birth Cohort (DNBC), which was established in 1996-2002. Blood samples were drawn at the time of enrollment (6-14 week of gestation). Serum levels of 10 perfluorocarboxylated acids (PFCAs), 5 perfluorosulfonated acids (PFSAs) and 1 sulfonamide (perflurooctane-sulfonamide, PFOSA) were measured. Genotyping was conducted for CYP1A1 (Ile462Val; rs1048943), CYP1B1 (Leu432Val; rs1056836), COMT (Val158Met; rs4680), CYP17A1 (A1→ A2; rs743572); CYP19A1 (C→T; rs10046) by the TaqMan allelic discrimination method. In overall, no significant associations were found between the investigated polymorphisms and the risk of breast cancer in this study among Danish women. The previously found association between PFOSA and risk of breast cancer did vary between different genotypes, with significantly increased risk confined to homozygous carriers of the following alleles: COMT (Met), CYP17 (A1) and CYP19 (C).

CONCLUSION: Our results indicate that polymorphisms in COMT, CYP17 and CYP19 which are involved in estrogen biosynthesis and metabolism can modulate the potential effects of PFOSA exposure on the development of breast cancer. 
Breast cancer; Genetic polymorphism; CYP1A1; CYP1B1; COMT; CYP17; CYP19 
• ^Per- and Polyfluoroalkyl Substances (PFAS)
     PFOA (335-67-1) and PFOS (1763-23-1)
          Literature Search – Adverse outcome pathway (2015-present)
               WOS
     PFOSA (754-91-6)
          Literature Search
               Pubmed
               WOS
• PFNA
     Literature Search
          Toxline
     PFNA May 2019 Update
          Toxnet
• PFOA (335-67-1) and PFOS (1763-23-1)
     Literature Search – Adverse outcome pathway (2015-present)
          WOS
     Screening Results
          Human/Epi studies
               Cancer
          Susceptible populations
     Literature Search Update (2013-2019)
          WOS
• PFOSA
     Literature Search
          Pubmed
          WOS
     Screening Results
          Human/Epi studies
               Cancer
          Susceptible populations