Prediction of breast cancer risk based on profiling with common genetic variants

BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

The artist biopic: a historical analysis of narrative cinema, 1934-2010

The thesis provides an historical overview of the artist biopic that has emerged as a distinct sub-genre of the biopic as a whole, totalling some ninety films from Europe and America alone since the first talking artist biopic in 1934. Their making usually reflects a determination on the part of the director or star to see the artist as an alter-ego. Many of them were adaptations of successful literary works, which tempted financial backers by having a ready-made audience based on a pre-established reputation. The sub-genre’s development is explored via the grouping of films with associated themes and the use of case studies. These examples can then be used as models for exploring similar sets of data from other countries and time periods. The specific topics chosen for discussion include the representation of a single painter, for example, Vincent Van Gogh, to see how the treatment of an artist varies across several countries and over seventy years. British artist biopics are analysed as a case study in relation to the idea of them posing as a national stereotype. Topics within sex and gender studies are highlighted in analysis of the representation of the female artist and the queer artist as well as artists who have lived together as couples. A number of well-known gallery artists have become directors of artist biopics and their films are considered to see what particular insights a professional working artist can bring to the portrayal of artistic genius and creation. In the concluding part of the thesis it is argued that the artist biopic overall has survived the bad press which some individual productions have received and can even be said to have matured under the influence of directors producing a quality product for the art house, festival and avant-garde distribution circuits. As a genre it has proved extremely adaptable and has reflected the changing attitudes towards art and artists within the wider community. It has both encouraged renewed interest in the work of established national artists and also raised the profile of those relatively obscure such as Séraphine de Senlis and Pirosmani.