Genetic variation at <i>CYP3A</i> is associated with age at menarche and breast cancer risk: a case-control study

Johnson, Nichola,Dudbridge, Frank,Orr, Nick,Gibson, Lorna,Jones, Michael E,Schoemaker, Minouk J,Folkerd, Elizabeth J,Haynes, Ben P,Hopper, John L,Southey, Melissa C,Dite, Gillian S,Apicella, Carmel,Sc BioMed Central 2014 Breast cancer research Vol.16 No.3

<P><B>Introduction</B></P><P>We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the <I>CYP3A</I> locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.</P><P><B>Methods</B></P><P>We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.</P><P><B>Results</B></P><P>We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; <I>P</I> = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; <I>P</I> = 0.004), respectively (<I>P</I><SUB>trend</SUB> = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (<I>P</I><SUB>trend</SUB> = 0.005) but not cases (<I>P</I><SUB>trend</SUB> = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (<I>P</I><SUB>het</SUB> = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR<SUB>het</SUB> = 0.84, 95% CI 0.75, 0.94; OR<SUB>hom</SUB> = 0.81, 95% CI 0.51, 1.30; <I>P</I><SUB>trend</SUB> = 0.002) but not for those who had their menarche age ≤11 years (OR<SUB>het</SUB> = 1.06, 95% CI 0.95, 1.19, OR<SUB>hom</SUB> = 1.07, 95% CI 0.67, 1.72; <I>P</I><SUB>trend</SUB> = 0.29).</P><P><B>Conclusions</B></P><P>To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.</P>

Missense Variants in ATM in 26,101 Breast Cancer Cases and 29,842 Controls.

Fletcher, Olivia,Johnson, Nichola,Dos Santos Silva, Isabel,Orr, Nick,Ashworth, Alan,Nevanlinna, Heli,Heikkinen, Tuomas,Aittomä,ki, Kristiina,Blomqvist, Carl,Burwinkel, Barbara,Bartram, Claus R,Mei American Association for Cancer Research 2010 Cancer Epidemiology, Biomarkers & Prevention Vol.19 No.9

<P>BACKGROUND: Truncating mutations in ATM have been shown to increase the risk of breast cancer but the effect of missense variants remains contentious. METHODS: We have genotyped five polymorphic (minor allele frequency, 0.9-2.6%) missense single nucleotide polymorphisms (SNP) in ATM (S49C, S707P, F858L, P1054R, and L1420F) in 26,101 breast cancer cases and 29,842 controls from 23 studies in the Breast Cancer Association Consortium. RESULTS: Combining the data from all five SNPs, the odds ratio (OR) was 1.05 for being a heterozygote for any of the SNPs and 1.51 for being a rare homozygote for any of the SNPs with an overall trend OR of 1.06 (P(trend) = 0.04). The trend OR among bilateral and familial cases was 1.12 (95% confidence interval, 1.02-1.23; P(trend) = 0.02). CONCLUSIONS: In this large combined analysis, these five missense ATM SNPs were associated with a small increased risk of breast cancer, explaining an estimated 0.03% of the excess familial risk of breast cancer. Impact: Testing the combined effects of rare missense variants in known breast cancer genes in large collaborative studies should clarify their overall contribution to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 19(9); 2143-51. ©2010 AACR.</P>

Mixed reality visualization in shoulder arthroplasty: is it better than traditional preoperative planning software?

Sejla Abdic,Nicholas J. Van Osch,Daniel G. Langohr,James A. Johnson,George S. Athwal 대한견주관절의학회 2023 대한견주관절의학회지 Vol.26 No.2

Background: Preoperative traditional software planning (TSP) is a method used to assist surgeons with implant selection and glenoid guide-pin insertion in shoulder arthroplasty. Mixed reality (MR) is a new technology that uses digital holograms of the preoperative plan and guide-pin trajectory projected into the operative field. The purpose of this study was to compare TSP to MR in a simulated surgical environment involving insertion of guide-pins into models of severely deformed glenoids. Methods: Eight surgeons inserted guide-pins into eight randomized three-dimensional-printed severely eroded glenoid models in a simulated surgical environment using either TSP or MR. In total, 128 glenoid models were used and statistically compared. The outcomes compared between techniques included procedural time, difference in guide-pin start point, difference in version and inclination, and surgeon confidence via a confidence rating scale. Results: When comparing traditional preoperative software planning to MR visualization as techniques to assist surgeons in glenoid guide pin insertion, there were no statistically significant differences in terms of mean procedure time (P=0.634), glenoid start-point (TSP=2.2±0.2 ㎜, MR=2.1±0.1 ㎜; P=0.760), guide-pin orientation (P=0.586), or confidence rating score (P=0.850). Conclusions: The results demonstrate that there were no significant differences between traditional preoperative software planning and MR visualization for guide-pin placement into models of eroded glenoids. A perceived benefit of MR is the real-time intraoperative visibility of the surgical plan and the patient’s anatomy; however, this did not translate into decreased procedural time or improved guide-pin position.

Microwave Heating and Pre-sintering of Copper Powder Metal Compacts in Separated Electric and Magnetic Fields

Zimmerman Darin T.,Johnson Earnie J.,Ma JunKun,Miskovsky Nicholas M.,Weisel Gary J.,Weiss Brock L. 한국분말야금학회 2006 한국분말야금학회 학술대회논문집 Vol.2006 No.1

We present a systematic study of the heating and pre-sintering behavior of porous copper powder metal compacts. We employ a TE102 single mode microwave system to position the samples in the separated electric field (E) or magnetic field (H) anti-node of the cavity. We observe significant differences in the heating, pre-sintering, and microstructure evolution of the samples due to the individual fields. We note that sample history (whether heated first in the E-field or H-field) greatly effects a difference in heating trends and subsequent heating behavior and does not appear to be solely a thermal process.

The global lambda visualization facility: An international ultra-high-definition wide-area visualization collaboratory

Leigh, Jason,Renambot, Luc,Johnson, Andrew,Jeong, Byungil,Jagodic, Ratko,Schwarz, Nicholas,Svistula, Dmitry,Singh, Rajvikram,Aguilera, Julieta,Wang, Xi,Vishwanath, Venkatram,Lopez, Brenda,Sandin, Dan Elsevier 2006 Future generation computer systems Vol.22 No.8

<P><B>Abstract</B></P><P>The research outlined in this paper marks an initial global cooperative effort between visualization and collaboration researchers to build a persistent virtual visualization facility linked by ultra-high-speed optical networks. The goal is to enable the comprehensive and synergistic research and development of the necessary hardware, software and interaction techniques to realize the next generation of end-user tools for scientists to collaborate on the global Lambda Grid. This paper outlines some of the visualization research projects that were demonstrated at the iGrid 2005 workshop in San Diego, California.</P>

Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2

Orr, Nick,Dudbridge, Frank,Dryden, Nicola,Maguire, Sarah,Novo, Daniela,Perrakis, Eleni,Johnson, Nichola,Ghoussaini, Maya,Hopper, John L.,Southey, Melissa C.,Apicella, Carmel,Stone, Jennifer,Schmidt, M IRL Press 2015 Human molecular genetics Vol.24 No.10

<P>We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88–0.92]; <I>P</I>-value = 1.58 × 10<SUP>−25</SUP>). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08–1.17]; <I>P</I>-value = 7.89 × 10<SUP>−09</SUP>) and rs13294895 (OR = 1.09 [1.06–1.12]; <I>P</I>-value = 2.97 × 10<SUP>−11</SUP>). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06–1.18]; <I>P</I>-value = 2.77 × 10<SUP>−05</SUP>). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. <I>In vitro</I> analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the <I>KLF4</I> gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.</P>

Nitrate-Containing Beetroot Juice Reduces Oxygen Consumption During Submaximal Exercise in Low but Not High Aerobically Fit Male Runners

( Colin R. Carriker ),( Roger A. Vaughan ),( Trisha A. Vandusseldorp ),( Kelly E. Johnson ),( Nicholas M. Beltz ),( James J. Mccormick ),( Nathan H. Cole ),( Ann L. Gibson ) 한국운동영양학회 2016 Physical Activity and Nutrition (Phys Act Nutr) Vol.20 No.4

[Purpose] To examine the effect of a 4-day NO₃- loading protocol on the submaximal oxygen cost of both low fit and high fit participants at five different exercise intensities. [Methods] Eleven (6 high fit, VO_2max 60.1 ± 4.6ml/kg/min; 5 low fit, VO_2max 42.4 ± 3.2ml/ kg/min) participants were initially assigned to a placebo (PL; negligible NO₃-) or inorganic nitrate-rich (NR; 6.2 mmol nitrate/day) group using a double-blind, placebo-controlled, crossover design. Participants completed three trials (T1, T2 and T3). T1 included a maximal aerobic capacity (VO_2max) treadmill test. A 6-day washout, minimizing nitrate consumption, preceded T2. Each of the four days prior to T2 and T3, participants consumed either PL or NR with the final dose 2.5 hours prior to exercise. A 14-day washout followed T2. T2 and T3 consisted of 5-minute submaximal treadmill bouts (45, 60, 70, 80 and 85% VO_2max) determined during T1. [Results] Low fit nitrate-supplemented participants consumed less oxygen (p<0.05) at lower workloads (45% and 60% VO_2max) compared to placebo trials; changes were not observed in high fit participants. The two lowest intensity workloads of 45 and 60% VO_2max revealed the greatest correlation (r=0.54, p=0.09 and r=0.79, p<0.05; respectively) between VO_2max and change in oxygen consumption. No differences were found between conditions for heart rate, respiratory exchange ratio or rating of perceived exertion for either fitness group. [Conclusion] Nitrate consumption promotes reduced oxygen consumption at lower exercise intensities in low fit, but not high fit males. Lesser fit individuals may receive greater benefit than higher fit participants exercising at intensities <60% VO_2max.

Identification and Molecular Analysis of Ixodid Ticks (Acari: Ixodidae) Infesting Domestic Animals and Tick-Borne Pathogens at the Tarim Basin of Southern Xinjiang, China

Li Zhao,Jizhou Lv,Fei Li,Kairui Li,Bo He,Luyao Zhang,Xueqing Han,Huiyu Wang,Nicholas Johnson,Xiangmei Lin,Shaoqiang Wu,Yonghong Liu 대한기생충학ㆍ열대의학회 2020 The Korean Journal of Parasitology Vol.58 No.1

Livestock husbandry is vital to economy of the Tarim Basin, Xinjiang Autonomous Region, China. However, there have been few surveys of the distribution of ixodid ticks (Acari: Ixodidae) and tick-borne pathogens affecting domestic animals at these locations. In this study, 3,916 adult ixodid ticks infesting domestic animals were collected from 23 sampling sites during 2012-2016. Ticks were identified to species based on morphology, and the identification was confirmed based on mitochondrial 16S and 12S rRNA sequences. Ten tick species belonging to 4 genera were identified, including Rhipicephalus turanicus, Hyalomma anatolicum, Rh. bursa, H. asiaticum asiaticum, and Rh. sanguineus. DNA sequences of Rickettsia spp. (spotted fever group) and Anaplasma spp. were detected in these ticks. Phylogenetic analyses revealed possible existence of undescribed Babesia spp. and Borrelia spp. This study illustrates potential threat to domestic animals and humans from tick-borne pathogens.