Breast cancer risk and serum levels of per- and poly-fluoroalkyl substances: a case-control study nested in the California Teachers Study

Abstract Background Per- and poly- fluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Their potential as breast carcinogens is unclear. Our objective was to evaluate the risk of breast cancer associated with serum PFAS concentrations in a nested case-control study within the California Teachers Study. Methods Participants were 902 women with invasive breast cancer (cases) and 858 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed during 2011–2015, an average of 35 months after case diagnosis. PFASs were measured using automated online SPE-HPLC-MS/MS methods. Statistical analyses were restricted to six PFASs with detection frequencies ≥ 95%: PFOA (Perfluorooctanoic acid), PFNA (Perfluorononanoic acid), PFUnDA (Perfluoroundecanoic acid), PFHxS (Perfluorohexane sulfonic acid), PFOS (Perfluorooctane sulfonic acid), and MeFOSAA (2-(N-Methyl-perfluorooctane sulfonamido) acetic acid. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs), estimating the breast cancer risk associated with each PFAS. Results For all cases of invasive breast cancer, none of the adjusted ORs were statistically significant but marginally significant ORs < 1.0 were observed for PFUnDA and PFHxS (p-trend = 0.08). Adjusted ORs < 1.0 for PFUnDA and PFHxS were statistically significant (p ≤ 0.05) among the 107 cases with hormone-negative tumors but not the 743 with hormone-positive tumors. Conclusion Overall, these findings do not provide evidence that serum PFAS levels measured after diagnosis are related to breast cancer risk. The few inverse associations found may be due to chance or may be artifacts of study design. Future studies should incorporate information about genetic susceptibility, endogenous estrogen levels, and measurements of PFASs prior to diagnosis and treatment

Sample Delivery Techniques for Serial Crystallography

In serial femtosecond crystallography (SFX), protein microcrystals and nanocrystals are introduced into the focus of an X-ray free electron laser (FEL) beam ideally one-by-one in a serial fashion. The high photon density in each pulse is the double-edged sword that necessitates the serial nature of the experiments. The high photon count focused spatially and temporally leads to a diffraction-before-destruction snapshot, but this single snapshot is not enough for a high-resolution three-dimensional structural reconstruction. To recover the structure, more snapshots are required to sample all of reciprocal space from randomly oriented crystal diffraction, and in practice, some redundancy is necessary in these measurements. This chapter explores the different sample delivery techniques developed over the years to help enable serial crystallography experiments