Parveen Bhatti

Background/Objectives: Demographic, health history, and lifestyle factors have been associated with prognosis of colorectal cancer (CRC), but the mechanisms underlying these associations remain poorly understood. Our primary objective was to explore the association of these factors with expression of two biomarkers in CRC, SPARC and PD-L1, for which lower and higher levels of expression, respectively, have been associated with poorer CRC prognosis. Methods: Participants were drawn from the British Columbia Generations Project (BCGP), who at time of recruitment, provided data on various demographic, health history, and lifestyle factors. Formalin-fixed paraffin-embedded blocks were obtained for 49 incident BCGP CRC cases and used to create tissue microarrays. Slides created from the microarrays were stained with SPARC and PD-L1 antibodies and analyzed to calculate H-scores as measures of expression in both epithelial and non-epithelial tissues. Linear regression analyses were used to evaluate associations between the various factors and ln-transformed H-scores.Results: In CRC tumour epithelium, smoking was associated with a 0.53-fold lower level of SPARC expression (p=0.05); a similar though non-significant, association was observed in non-epithelial tumour tissue. Higher income was associated with a 1.33-fold greater level of SPARC expression in tumor non-epithelial tissue (p=0.04); a similar effect was not observed in tumour epithelium. Higher stage was associated with a 0.74-fold lower level of non-epithelial tumour SPARC expression (p=0.04). A similar non-significant effect was observed in tumour epithelium. PD-L1 expression in tumour epithelium was 2.84-fold greater among females (p=0.005). A similar non-significant effect was observed in tumour non-epithelial tissue. History of CRC screening was statistically significantly associated with 2-fold greater levels of PD-L1 expression in tumour epithelial and non-epithelial tissues (p=0.04). Conclusion: Associations of SPARC expression with smoking, income, and stage, but not PD-L1 expression with biological sex and history of CRC screening, were consistent with the previously established associations of these factors with CRC prognosis. Larger scale studies with prognostic data are needed, but our results suggest that differences in expression of SPARC may contribute to the previously observed impacts of factors on CRC prognosis. However, additional work to understand the role of PD-L1 in CRC prognosis is needed.

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Background. By suppressing secretion of melatonin, outdoor artificial light at night (ALAN) may increase risk of breast cancer. Previous studies of ALAN and breast cancer have produced mixed results, which may be attributable to ALAN measures that did not account for wavelength of light; suppression of melatonin by ALAN is influenced by both light intensity and wavelength. Methods. We conducted a study of 318 breast cancer cases and 3180 controls nested within the British Columbia Generations Project (BCGP). Measures of ALAN were generated from colour images captured from the International Space Station (ISS) and linked to participant residential addresses. Measures included visual radiance (i.e., brightness), melatonin suppression index (MSI), which quantifies the extent to which light spectra suppress melatonin, and the product of visual radiance and MSI (Impact MSI). Unconditional logistic regression models, adjusted for matching factors, were used to evaluate associations between ALAN exposure and breast cancer risk. Odds ratios (OR) with 95% confidence intervals (CI) were generated as estimates of relative risk. In exploratory analyses, we evaluated associations with individual breast cancer hormone receptor subtypes as well as associations when excluding participants that reported working night or rotating shifts at time of recruitment and when restricting to participants reporting light entering their rooms when sleeping. Results. No statistically significant associations between ALAN measures and breast cancer risk overall or with specific tumour receptor subtypes were observed. In analyses restricting to those participants reporting light entering their rooms while sleeping, a statistically significant 42% increase in risk of breast cancer was seen when comparing the highest to lowest tertiles of Impact MSI (95% CI: 1.05-1.92). Conclusions. While we did not find evidence of an overall relationship between outdoor ALAN and breast cancer risk, exploratory analyses restricted to participants reporting light entering their rooms while sleeping suggested an increased risk of breast cancer among those most highly exposed. This association was specifically found with an ALAN measure that accounted for both aspects of light exposure that impact melatonin secretion: intensity and wavelength. To confirm these findings, a larger-scale pooled study using similarly collected data from other cohorts is warranted.

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