Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

Milne, Roger L.,Burwinkel, Barbara,Michailidou, Kyriaki,Arias-Perez, Jose-Ignacio,Zamora, M. Pilar,Mené,ndez-Rodrí,guez, Primitiva,Hardisson, David,Mendiola, Marta,Gonzá,lez-Neira, A IRL Press 2014 Human molecular genetics Vol.23 No.22

<P>Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: <I>ATXN7-</I>K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04–1.10, <I>P</I> = 2.9 × 10<SUP>−6</SUP>], <I>AKAP9-</I>M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03–1.07, <I>P</I> = 1.7 × 10<SUP>−6</SUP>) and <I>NEK10-</I>L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07–1.12, <I>P</I> = 5.1 × 10<SUP>−17</SUP>). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for <I>ATXN7-</I>K264R, OR = 1.07 (95% CI = 1.05–1.10, <I>P</I> = 1.0 × 10<SUP>−8</SUP>); for <I>AKAP9-</I>M463I, OR = 1.05 (95% CI = 1.04–1.07, <I>P</I> = 2.0 × 10<SUP>−10</SUP>). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.</P>

A Cosmopolitical Philosophy to Come : Derrida and the Ends of Humanity

Milne, Peter 이화여자대학교 이화인문과학원 2012 탈경계 인문학 Vol.5 No.1

Although Derrida is often taken to be “anti-humanist,” this paper argues that his engagement with the legacy of humanism is not only much more complex, but that it retains and alters this legacy in such a way as to provide a new way of thinking about the human in a trans-national or “global” context. This argument is at the same time an occasion to briefly explore some of the implications of this for Derrida’s relation to philosophy as a humanistic discipline. It first tracks some of Derrida’s most explicit discussions of humanism over the course of several works and lines of inquiry, showing what I take to be a shift in his work from the critical stance of “The Ends of Man” to the more nuanced discussions in some of the later “political” writings. My main goal is to link Derrida’s discussions of humanism to his work on cosmopolitanism and particularly to his argument that political thinking must negotiate the troubling but important legacy of a philosophical universalism that is nonetheless tied to a very particular cultural and historical past. I take this problem to be analogous to the ambiguity of a humanist legacy that is potentially violent and limiting in its conception of universal humanity while being at the same time what underwrites important political concepts such as human rights. Derrida argues that philosophy is the “other way” and is thus always open to redirection and reap- propriation by traditions other than its own. Taking the “human” as an Idea in the Kantian sense, I argue that it too can wander from its end, liberate itself from the strictures of universal humanity while nonetheless retaining the promise and the political consideration due that humanity. Derrida thus offers an innovative way to rethink the humanist legacy in the context of a plurality of cultures. I end by suggesting that philosophy and the humanities more generally, far from being irrelevant, may thus be more relevant than ever.

Hepatitis B Immunisation : An Update

Milne, Alexander,Lucas, C.Ron Medical Publications Korea 1994 Medical Progress Vol.16 No.2

Risk of Estrogen Receptor-Positive and -Negative Breast Cancer and Single-Nucleotide Polymorphism 2q35-rs13387042

Milne, Roger L.,Bení,tez, Javier,Nevanlinna, Heli,Heikkinen, Tuomas,Aittomä,ki, Kristiina,Blomqvist, Carl,Arias, José,Ignacio,Zamora, M. Pilar,Burwinkel, Barbara,Bartram, Claus R.,Mein Oxford University Press 2009 Journal of the National Cancer Institute Vol.101 No.14

<P>BACKGROUND: A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium. METHODS: 2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided. RESULTS: We found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P > or = .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002). CONCLUSION: The rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.</P>

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer

Milne, Roger L,Kuchenbaecker, Karoline B,Michailidou, Kyriaki,Beesley, Jonathan,Kar, Siddhartha,Lindströ,m, Sara,Hui, Shirley,Lemaç,on, Audrey,Soucy, Penny,Dennis, Joe,Jiang, Xia,Rostamianfa Nature Pub. Co 2017 Nature genetics Vol.49 No.12

<P>Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease(1). We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 x 10(-8) with ten variants at nine new loci. At P < 0.05, we replicated associations with 10 of 11 variants previously reported in ER-negative disease or BRCA1 mutation carrier GWAS and observed consistent associations with ER-negative disease for 105 susceptibility variants identified by other studies. These 125 variants explain approximately 16% of the familial risk of this breast cancer subtype. There was high genetic correlation (0.72) between risk of ER-negative breast cancer and breast cancer risk for BRCA1 mutation carriers. These findings may lead to improved risk prediction and inform further fine-mapping and functional work to better understand the biological basis of ER-negative breast cancer.</P>

The consumer in the information society

Claire Milne 정보통신정책연구원 1996 세미나및공청회 Vol.1996 No.

DEEP DARK OASIS IN THE UNKNOWN SEA CANYONS

H. J. Milne,T. S. Gallagher,D. Leduc 국제과학영재학회 2008 APEC Youth Scientist Journal Vol.1 No.-

Taking the Body as Model ‒Lyotard and Reflection‒

Peter W. Milne 한국철학회 2019 哲學 Vol.- No.141

This paper takes as its object two writings by the “late” Lyotard on the notion of reflection. While Lyotard’s best known and most sustained engagement with this notion is to be found in his various writings on Kant, and particularly in the first chapter of the Leçons sur l’Analytique du sublime, this study contextualizes this discussion in terms of an earlier essay, “Si l’on peut penser sans corps.” The rationale for this is to attempt to situate the more technical discussion of Kant in the Leçons in terms of some of the broader concerns of the late Lyotard’s work on the affect, particularly with regard to the relation of the latter to both thinking and the body.

Enframing: Art’s Epoche and the Promethean Community

Peter W. Milne 이화여자대학교 이화인문과학원 2014 탈경계인문학 Vol.7 No.3

This essay takes as its point of departure a little known text by Jean-François Lyotard on art and its relation to global networks of telecommunication in order to explore the possibilities for social and political communities in the context of global capital. Borrowing Heidegger’s notion of an “enframing” (Gestell) of nature by technology, Lyotard inquires into a similar enframing of art, arguing that art, through the very fact that it is an unprogrammable kind of techne, has the power to “suspend” the programs of what he calls “capitalist technoscience,” and in so doing works against the loss of originality such programs produce. Linking this to Lyotard’s famous discussion of the avantgarde, I examine the potential political force of such a suspension or “epoche,” particularly with regard to the formation of possible publics in the absence of world historical “grand narratives” that would situate a universal human subject within a particular conception of historical progress. Lyotard argues that the Idea (in the Kantian sense) of totality no longer unproblematically provides the horizon for political thought. Any such cosmopolitan community is therefore problematic, communities can only be formed in the absence of necessarily shared qualities or traits. They must therefore be “promethean” in the sense of being creative, daring, and open to reinterpretation. Not only is this not something to be lamented, however, it is something that should be affirmed for the open possibilities it offers.

In Statu Nascendi: Subjectivity and the Beautiful in Lyotard

( Peter W. Milne ) 한국미학회 2020 美學 Vol.86 No.4

While Lyotard’s interest in the sublime is well known, his later investigations of the beautiful are much less so. In part this seems to have to do with his own evolving views toward the beautiful as an aesthetic category, which in much of his best-known writings appears mostly to be aligned with representation and thus with Classicism and the Enlightenment. Nonetheless, there is another and more subtle understanding of the beautiful to be found in Lyotard, where it is even found alongside the sublime and what he calls, following Freud, “unconscious affect.” In these works, the beautiful appears to take on another relevance, and may even help us to begin to take the full measure of the “philosophy of the affect” that Lyotard seems to be largely engaged in during many of his last writings. This essay is an attempt to begin this process by giving a detailed reading of one of the major of these texts, in order, on the one hand, to show how the beautiful comes to be counted alongside the sublime and unconscious affect, and on the other, to make some suggestions about how it differs from them and might thus offer a broader understanding of Lyotard’s late account of affectivity. This reading of the beautiful appears most clearly in an essay devoted to the Kantian judgment of taste entitled “Sensus Communis.” I try to elucidate the main contours of this argument in terms of the split in Kant’s sensus communis that Lyotard introduces there: a communis that is formed not by any shared sensibility but by the “voices” of the faculties themselves; and the sentiment of beauty as a sensus that exceeds not only the faculties of knowledge and action but even the conscious subject itself. As with the later conception of the sublime and unconscious affect, the beautiful here appears as a very specific “temporal crisis” that undoes the temporalization of the subject. In this sense, it is consistent with other readings of the affect in this stage of Lyotard’s writings. Nonetheless, it also differs in that it is time in statu nascendi, in the state of birth, and as a result I argue that it seems to figure a certain promise that is absent in both the sublime and unconscious affect, even if that promise is always and only ever to come.