Approximately two-thirds of breast cancers express the estrogen receptor, and prolonged estrogen exposure is a known risk factor for breast cancer development. Estrogen's non-genomic actions involve the rapid activation of Gq/11 signaling, which triggers downstream pathways such as calcium signaling and PKC activation. These pathways play a crucial role in regulating cellular growth, differentiation, and proliferation, particularly in breast cancer and other estrogen-sensitive tissues.
Chakraborty A, Pramanik S, Datta K, Goswami R, Saha D, Majumdar KK, Sikdar N - "Possible Association Between Polymorphisms in ESR1, COL1A2, BGLAP, SPARC, VDR, and MMP2 Genes and Dental Fluorosis in a Population from an Endemic Region of West Bengal" Biol Trace Elem Res 200(11):4641-4653 (2022) doi: 10.1007/s12011-021-03072-8
The best model of MDR analysis with maximized testing accuracy involved two SNPs from the ESR1 gene (rs9340799 and rs2077647) and one SNP from BGLAP gene (rs1543294) (P value < 0.0001).
Chen L, Yin N, Ding Y, Zhang ML, Li M, Zhong JJ, Feng SM - "Effects of fluoride on the proliferation and activation of osteoblasts by regulating methylation of the DNA repair genes MGMT and MLH1" Regen Ther 19:107-112 (2022) doi: 10.1016/j.reth.2022.01.004
https://www.sciencedirect.com/science/a ... 0422000049
Chen's study showed that low doses of fluoride increased methylation of MGMT and MLH1 in osteoblasts, leading to reduced expression of these genes. In breast cancer, particularly basal-like breast cancer (BLBC), the reduced expression of MGMT and MLH1 is linked to tumor progression and poorer survival.
Dalledone M, Cunha AS, Ramazzotto LA, Pecharki GD, Nelson-Filho P, Scariot R, Trevilatto PC, Vieira AR, Küchler EC, Brancher JA - "Estrogen receptor gene is associated with dental fluorosis in Brazilian children" Clin Oral Investig 23(9):3565-3570 (2019). doi: 10.1007/s00784-018-2778-2
https://link.springer.com/article/10.10 ... 018-2778-2
Dou Q, Bai Y, Li Y, Zheng S, Wang M, Wang Z, Sun J, Zhang D, Yin C, Ma L, Lu Y, Zhang L, Chen R, Cheng Z - "Perfluoroalkyl substances exposure and the risk of breast cancer: A nested case-control study in Jinchang Cohort" Environ Res 262(Pt 2):119909 (2024). doi: 10.1016/j.envres.2024.119909.
https://linkinghub.elsevier.com/retriev ... 24)01814-0
"Exposures to specific PFAS components were positively associated with an increased incidence risk of breast cancer...Random forests showed that PFBA, PFOS, PFHxS, and PFDA emerged as predominant factors potentially influencing breast cancer incidence....Our findings suggest a strong association between PFAS exposure and the incidence of breast cancer. Premenopausal women should exercise more caution regarding PFAS exposure."
Liu Q, Liu Y, Li X, Wang D, Zhang A, Pang J, He J, Chen X, Tang NJ - "Perfluoroalkyl substances promote breast cancer progression via ERα and GPER mediated PI3K/Akt and MAPK/Erk signaling pathways" Ecotoxicol Environ Saf 258:114980 (2023) . doi: 10.1016/j.ecoenv.2023.114980
https://www.sciencedirect.com/science/a ... 1323004840
"Two estrogen receptors (ER), ERα and G protein-coupled estrogen receptor (GPER), mediated the promoting effects of PFOA by activating MAPK/Erk and PI3K/Akt signaling pathways. These pathways were regulated by ERα and GPER in MCF-7 cells or independently by GPER in MDA-MB-231 cells. Overall, our study provides a better overview of the mechanisms associated with PFASs-induced breast cancer development and progression."
Ma Q, Huang H, Sun L, Zhou T, Zhu J, Cheng X, Duan L, Li Z, Cui L, Ba Y - "Gene-environment interaction: Does fluoride influence the reproductive hormones in male farmers modified by ERα gene polymorphisms?" Chemosphere 188:525-531 (2017). doi: 10.1016/j.chemosphere.2017.08.166
https://preview.ncbi.nlm.nih.gov/pubmed/28910727
Maras M, Vanparys C, Muylle F, Robbens J, Berger U, Barber JL, Blust R, De Coen W - "Estrogen-like properties of fluorotelomer alcohols as revealed by mcf-7 breast cancer cell proliferation" Environ Health Perspect 114(1):100-5 (2006). doi: 10.1289/ehp.8149
https://pubmed.ncbi.nlm.nih.gov/16393665/
"We observed small but relevant up-regulation of the estrogen receptor as a consequence of exposures to 6:2 FTOH or 8:2 FTOH. The latter finding suggests an alternative mode of action of the fluorotelomer alcohols compared with that of E2. This study clearly underlines the need for future in vivo testing for specific endocrine-related end points."
- SEE also: FTOH & Dental Fluorosis - PFAS: viewtopic.php?f=6&t=1581
https://link.springer.com/article/10.10 ... 009-0050-x
"This area of endemic fluorosis has a high incidence of subclinical hypothyroidism (2-10%). This geographical area has also a very high incidence of breast cancer (16.2%). The drinking water level of fluoride is 5.2 ppm in this area."
Song L, Wang W, Liu D, Zhao Y, He J, Wang X, Dai Z, Zhang H, Li X - "Targeting of sonic hedgehog-Gli signaling: A potential therapeutic target for patients with breast cancer" Oncol Lett 12(2):1027-1033 (2016). doi: 10.3892/ol.2016.4722
https://www.spandidos-publications.com/ ... .2016.4722
As documented elsewhere on this site, Sonic Hedgehog (Shh) is a thyroid-responsive gene involved in fluorosis. Song et al. demonstrated that Shh-Gli signaling is significantly activated in breast cancer cells, enhancing cell viability and proliferation through the upregulation of Bcl-2 and cyclin D1 (--> Gq/11 modulates Shh-Gli activity).
- SEE also:
Budimir I, Tomasović-Lončarić Č, Kralik K, Čonkaš J, Eljuga D, Žic R, Gorjanc B, Tucaković H, Caktaš D, Jaman J, Lisek V, Vlajčić Z, Martić K, Ozretić P - "Higher Expressions of SHH and AR Are Associated with a Positive Receptor Status and Have Impact on Survival in a Cohort of Croatian Breast Cancer Patients" Life (Basel) 12(10):1559 (2022) doi: 10.3390/life12101559
https://www.mdpi.com/2075-1729/12/10/1559
https://www.sciencedirect.com/science/a ... 2020318055
•PFOS was associated with breast cancer risk in Taiwanese women.
•Young women (age ≤ 50 years) had a high risk of breast cancer by PFOS exposure.
•Women in the age less than 50 years had a higher risk of estrogen receptor positive tumors than those in the age over 50 years by PFHxS and PFOS exposure.
Zhou G, Ren L, Hou J, Cui L, Ding Z, Cheng X, Zhu J, Cui R, Ba Y - "Endemic fluorosis in Henan province, China: ERα gene polymorphisms and reproductive hormones among women" Asia Pac J Clin Nutr 25(4):911–919 (2016)
https://pubmed.ncbi.nlm.nih.gov/27702735/