Genetics and Epidemiology
https://repository.icr.ac.uk/handle/internal/6
2024-03-28T19:06:26ZMosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study.
https://repository.icr.ac.uk/handle/internal/6179
Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study.
Olivos, N; Banta, JE; Spencer-Hwang, R; Ansong, D; Beane Freeman, LE; Clegg-Lamptey, J-N; Wiafe-Addai, B; Edusei, L; Adjei, E; Titiloye, N; Dedey, F; Aitpillah, F; Oppong, J; Vanderpuye, V; Osei-Bonsu, E; Ahearn, TU; Biritwum, R; Yarney, J; Awuah, B; Nyarko, K; Garcia-Closas, M; Abubakar, M; Brinton, LA; Figueroa, JD; Wiafe, S
Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (ORadj) and 95% confidence intervals (CI) with breast cancer risk-adjusted for potential confounders and known risk factors. Among controls, the reported use of mosquito control products were mosquito coils (65%), followed by insecticide-treated nets (56%), repellent room sprays (53%), and repellent skin creams (15%). Compared to a referent group of participants unexposed to mosquito control products, there was no significant association between breast cancer risk and mosquito coils. There was an association in breast cancer risk with reported use of insecticide-treated nets; however, that association was weak and not statistically significant. Participants who reported using repellent sprays were at elevated risks compared to women who did not use any mosquito control products, even after adjustment for all other mosquito control products (OR = 1.42, 95% CI=1.15-1.75). We had limited power to detect an association with repellent skin creams. Although only a few participants reported using repellent room sprays weekly/daily or < month-monthly, no trends were evident with increased frequency of use of repellent sprays, and there was no statistical evidence of heterogeneity by estrogen receptor (ER) status (p-het > 0.25). Our analysis was limited when determining if an association existed with repellent skin creams; therefore, we cannot conclude an association. We found limited evidence of risk associations with widely used mosquito coils and insecticide-treated nets, which are reassuring given their importance for malaria prevention. Our findings regarding specific breast cancer risk associations, specifically those observed between repellent sprays, require further study.
2023-12-11T00:00:00ZPhenome-wide Mendelian randomisation analysis of 378,142 cases reveals risk factors for eight common cancers.
https://repository.icr.ac.uk/handle/internal/6162
Phenome-wide Mendelian randomisation analysis of 378,142 cases reveals risk factors for eight common cancers.
Went, M; Sud, A; Mills, C; Hyde, A; Culliford, R; Law, P; Vijayakrishnan, J; Gockel, I; Maj, C; Schumacher, J; Palles, C; Kaiser, M; Houlston, R
For many cancers there are only a few well-established risk factors. Here, we use summary data from genome-wide association studies (GWAS) in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to identify potentially causal relationships for over 3,000 traits. Our outcome datasets comprise 378,142 cases across breast, prostate, colorectal, lung, endometrial, oesophageal, renal, and ovarian cancers, as well as 485,715 controls. We complement this analysis by systematically mining the literature space for supporting evidence. In addition to providing supporting evidence for well-established risk factors (smoking, alcohol, obesity, lack of physical activity), we also find sex steroid hormones, plasma lipids, and telomere length as determinants of cancer risk. A number of the molecular factors we identify may prove to be potential biomarkers. Our analysis, which highlights aetiological similarities and differences in common cancers, should aid public health prevention strategies to reduce cancer burden. We provide a R/Shiny app to visualise findings.
2024-03-25T00:00:00ZPhenotypic noise and plasticity in cancer evolution.
https://repository.icr.ac.uk/handle/internal/6153
Phenotypic noise and plasticity in cancer evolution.
Whiting, FJH; Househam, J; Baker, A-M; Sottoriva, A; Graham, TA
Non-genetic alterations can produce changes in a cell's phenotype. In cancer, these phenomena can influence a cell's fitness by conferring access to heritable, beneficial phenotypes. Herein, we argue that current discussions of 'phenotypic plasticity' in cancer evolution ignore a salient feature of the original definition: namely, that it occurs in response to an environmental change. We suggest 'phenotypic noise' be used to distinguish non-genetic changes in phenotype that occur independently from the environment. We discuss the conceptual and methodological techniques used to identify these phenomena during cancer evolution. We propose that the distinction will guide efforts to define mechanisms of phenotype change, accelerate translational work to manipulate phenotypes through treatment, and, ultimately, improve patient outcomes.
2023-11-13T00:00:00ZImpact of germline DNA repair gene variants on prognosis and treatment of men with advanced prostate cancer.
https://repository.icr.ac.uk/handle/internal/6133
Impact of germline DNA repair gene variants on prognosis and treatment of men with advanced prostate cancer.
Hansen, EB; Karlsson, Q; Merson, S; Wakerell, S; Rageevakumar, R; Jensen, JB; Borre, M; Kote-Jarai, Z; Eeles, RA; Sørensen, KD
The clinical importance of germline variants in DNA repair genes (DRGs) is becoming increasingly recognized, but their impact on advanced prostate cancer prognosis remains unclear. A cohort of 221 newly diagnosed metastatic castration-resistant prostate cancer (mCRPC) patients were screened for pathogenic germline variants in 114 DRGs. The primary endpoint was progression-free survival (PFS) on first-line androgen signaling inhibitor (ARSI) treatment for mCRPC. Secondary endpoints were time to mCRPC progression on initial androgen deprivation therapy (ADT) and overall survival (OS). Twenty-seven patients (12.2%) carried a germline DRG variant. DRG carrier status was independently associated with shorter PFS on first-line ARSI [HR 1.72 (1.06-2.81), P = 0.029]. At initiation of ADT, DRG carrier status was independently associated with shorter progression time to mCRPC [HR 1.56, (1.02-2.39), P = 0.04] and shorter OS [HR 1.99, (1.12-3.52), P = 0.02]. Investigating the contributions of individual germline DRG variants on PFS and OS revealed CHEK2 variants to have little effect. Furthermore, prior taxane treatment was associated with worse PFS on first-line ARSI for DRG carriers excluding CHEK2 (P = 0.0001), but not for noncarriers. In conclusion, germline DRG carrier status holds independent prognostic value for predicting advanced prostate cancer patient outcomes and may potentially inform on optimal treatment sequencing already at the hormone-sensitive stage.
2023-11-06T00:00:00Z