Patricia McKinney

Publications of Patricia McKinney

• A novel approach to exploring potential interactions among single-nucleotide polymorphisms of inflammation genes in gliomagenesis: an exploratory case-only study.

  Authors: E Susan Amirian, Michael E Scheurer, Yanhong Liu, Anthony M D'Amelio, Richard S Houlston, Carol J Etzel, Sanjay Shete, Anthony J Swerdlow, Minouk J Schoemaker, Patricia A McKinney, Sarah J Fleming, Kenneth R Muir, Artitaya Lophatananon, Melissa L Bondy

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 07/2011; 20(8):1683-9.

  Despite extensive research on the topic, glioma etiology remains largely unknown. Exploration of potential interactions between single-nucleotide polymorphisms (SNP) of immune genes is a promisingDespite extensive research on the topic, glioma etiology remains largely unknown. Exploration of potential interactions between single-nucleotide polymorphisms (SNP) of immune genes is a promising new area of glioma research. The case-only study design is a powerful and efficient design for exploring possible multiplicative interactions between factors that are independent of one another. The purpose of our study was to use this exploratory design to identify potential pair wise SNP-SNP interactions from genes involved in several different immune-related pathways for investigation in future studies. The study population consisted of two case groups: 1,224 histologic confirmed, non-Hispanic white glioma cases from the United States and a validation population of 634 glioma cases from the United Kingdom. Polytomous logistic regression, in which one SNP was coded as the outcome and the other SNP was included as the exposure, was utilized to calculate the ORs of the likelihood of cases simultaneously having the variant alleles of two different SNPs. Potential interactions were examined only between SNPs located in different genes or chromosomes. Using this data mining strategy, we found 396 significant SNP-SNP interactions among polymorphisms of immune-related genes that were present in both the U.S. and U.K. study populations. This exploratory study was conducted for the purpose of hypothesis generation, and thus has provided several new hypotheses that can be tested using traditional case-control study designs to obtain estimates of risk. This is the first study, to our knowledge, to take this novel approach to identifying SNP-SNP interactions relevant to glioma etiology.

• CASP8 D302H and meningioma risk: An analysis of five case-control series.

  Authors: Lara Bethke, Kate Sullivan, Emily Webb, Anne Murray, Minouk Schoemaker, Anssi Auvinen, Anne Kiuru, Tiina Salminen, Christoffer Johansen, Helle Collatz Christensen [......] Sarah Hepworth, Polyxeni Dimitropoulou, Artitaya Lophatananon, Maria Feychting, Stefan Lönn, Anders Ahlbom, Beatrice Malmer, Roger Henriksson, Anthony Swerdlow, Richard Houlston

  Cancer letters. 10/2008;

  Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and hence a defence against cancer. The CASP8 polymorphism D302H has recently been shown to influence the risk of breastCaspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and hence a defence against cancer. The CASP8 polymorphism D302H has recently been shown to influence the risk of breast cancer. We tested the hypothesis that the CASP8 polymorphism D302H may influence risk of meningioma through analysis of five independent series of case patients and controls (n=631 and 637, respectively). Carrier status for 302H was not associated with a statistically significantly increased risk (OR=1.16; 95% CI: 0.87-1.53; P=0.31) making it unlikely that this variant contributes to the inherited risk of meningioma.

• Functional polymorphisms in folate metabolism genes influence the risk of meningioma and glioma.

  Authors: Lara Bethke, Emily Webb, Anne Murray, Minouk Schoemaker, Maria Feychting, Stefan Lönn, Anders Ahlbom, Beatrice Malmer, Roger Henriksson, Anssi Auvinen [......] Tiina Salminen, Christoffer Johansen, Helle Collatz Christensen, Kenneth Muir, Patricia McKinney, Sarah Hepworth, Polyxeni Dimitropoulou, Artitaya Lophatananon, Anthony Swerdlow, Richard Houlston

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 06/2008; 17(5):1195-202.

  Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR),Folate metabolism plays an important role in carcinogenesis. To test the hypothesis that polymorphic variation in the folate metabolism genes 5,10-methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTRR), and methionine synthase reductase (MTR) influences the risk of primary brain tumors, we genotyped 1,005 glioma cases, 631 meningioma cases, and 1,101 controls for the MTHFR C677A and A1298C, MTRR A66G, and MTR A2756G variants. MTHFR C677T-A1298C diplotypes were associated with risk of meningioma (P = 0.002) and glioma (P = 0.02); risks were increased with genotypes associated with reduced MTHFR activity. The highest risk of meningioma was associated with heterozygosity for both MTHFR variants [odds ratio (OR), 2.11; 95% confidence interval (95% CI), 1.42-3.12]. The corresponding OR for glioma was 1.23 (95% CI, 0.91-1.66). A significant association between risk of meningioma and homozygosity for MTRR 66G was also observed (OR, 1.41; 95% CI, 1.02-1.94). Our findings provide support for the role of folate metabolism in the development of primary brain tumors. In particular, genotypes associated with increased 5,10-methylenetetrahydrofolate levels are associated with elevated risk.

• The common D302H variant of CASP8 is associated with risk of glioma.

  Authors: Lara Bethke, Kate Sullivan, Emily Webb, Anne Murray, Minouk Schoemaker, Anssi Auvinen, Anne Kiuru, Tiina Salminen, Christoffer Johansen, Helle Collatz Christensen [......] Sarah Hepworth, Polyxeni Dimitropoulou, Artitaya Lophatananon, Maria Feychting, Stefan Lönn, Anders Ahlbom, Beatrice Malmer, Roger Henriksson, Anthony Swerdlow, Richard Houlston

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 05/2008; 17(4):987-9.

  Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and, hence, a defense against cancer. We tested the hypothesis that the CASP8 polymorphism D302H influences risk of gliomaCaspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and, hence, a defense against cancer. We tested the hypothesis that the CASP8 polymorphism D302H influences risk of glioma through analysis of five series of glioma case patients and controls (n = 1,005 and 1,011, respectively). Carrier status for the rare allele of D302H was associated with a 1.37-fold increased risk (95% confidence interval, 1.10-1.70; P = 0.004). The association of CASP8 D302H with glioma risk indicates the importance of inherited variation in the apoptosis pathway in susceptibility to this form of primary brain tumor.

• Comprehensive analysis of the role of DNA repair gene polymorphisms on risk of glioma.

  Authors: Lara Bethke, Emily Webb, Anne Murray, Minouk Schoemaker, Christoffer Johansen, Helle Collatz Christensen, Kenneth Muir, Patricia McKinney, Sarah Hepworth, Polyxeni Dimitropoulou [......] Maria Feychting, Stefan Lönn, Anders Ahlbom, Beatrice Malmer, Roger Henriksson, Anssi Auvinen, Anne Kiuru, Tiina Salminen, Anthony Swerdlow, Richard Houlston

  Human molecular genetics. 04/2008; 17(6):800-5.

  Much of the variation in inherited risk of glioma is likely to be explained by combinations of common low risk variants. The established relationship between glioma risk and exposure to ionizingMuch of the variation in inherited risk of glioma is likely to be explained by combinations of common low risk variants. The established relationship between glioma risk and exposure to ionizing radiation led us to examine whether variants in the DNA repair genes contribute to disease susceptibility. We evaluated 1127 haplotype-tagging single-nucleotide polymorphisms (SNPs) supplemented with 388 putative functional SNPs to capture most of the common variation in 136 DNA repair genes, in five unique case-control series from four different countries (1013 cases, 1016 controls). We identified 16 SNPs associated with glioma risk at the 1% significance level. The highest association observed across the five independent case-control datasets involved rs243356, which maps to intron 3 of CHAF1A (trend odds ratio, 1.32; 95% confidence interval 1.14-1.54; P = 0.0002; false-positive report probability = 0.055, based on a prior probability of 0.01). Our results provide additional support for the hypothesis that low penetrance variants contribute to the risk of developing glioma and suggest that a genetic variant located in or around the CHAF1A gene contributes to disease risk.

• Comprehensive analysis of DNA repair gene variants and risk of meningioma.

  Authors: Lara Bethke, Anne Murray, Emily Webb, Minouk Schoemaker, Kenneth Muir, Patricia McKinney, Sarah Hepworth, Polyxeni Dimitropoulou, Artitaya Lophatananon, Maria Feychting [......] Beatrice Malmer, Roger Henriksson, Anssi Auvinen, Anne Kiuru, Tiina Salminen, Christoffer Johansen, Helle Collatz Christensen, Michael Kosteljanetz, Anthony Swerdlow, Richard Houlston

  Journal of the National Cancer Institute. 03/2008; 100(4):270-6.

  BACKGROUND: Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients beingBACKGROUND: Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility. METHODS: We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case-control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided. RESULTS: The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1-interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; P(trend) = 8.95 x 10(-6); P = .009 after adjusting for multiple testing). CONCLUSIONS: We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma.

• The INTERPHONE study: design, epidemiological methods, and description of the study population.

  Authors: Elisabeth Cardis, Lesley Richardson, Isabelle Deltour, Bruce Armstrong, Maria Feychting, Christoffer Johansen, Monique Kilkenny, Patricia McKinney, Baruch Modan, Siegal Sadetzki [......] Brigitte Schlehofer, Jack Siemiatycki, Masao Taki, Toru Takebayashi, Tore Tynes, Martie van Tongeren, Paolo Vecchia, Joe Wiart, Alistair Woodward, Naohito Yamaguchi

  European journal of epidemiology. 02/2007; 22(9):647-64.

  The very rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. A multinationalThe very rapid worldwide increase in mobile phone use in the last decade has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. A multinational case-control study, INTERPHONE, was set-up to investigate whether mobile phone use increases the risk of cancer and, more specifically, whether the RF fields emitted by mobile phones are carcinogenic. The study focused on tumours arising in the tissues most exposed to RF fields from mobile phones: glioma, meningioma, acoustic neurinoma and parotid gland tumours. In addition to a detailed history of mobile phone use, information was collected on a number of known and potential risk factors for these tumours. The study was conducted in 13 countries. Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the UK using a common core protocol. This paper describes the study design and methods and the main characteristics of the study population. INTERPHONE is the largest case-control study to date investigating risks related to mobile phone use and to other potential risk factors for the tumours of interest and includes 2,765 glioma, 2,425 meningioma, 1,121 acoustic neurinoma, 109 malignant parotid gland tumour cases and 7,658 controls. Particular attention was paid to estimating the amount and direction of potential recall and participation biases and their impact on the study results.

• Childhood cancer and power lines: What do the data mean?

  Authors: Nick Day, Tim Eden, Patricia McKinney, Eve Roman, Jill Simpson

  BMJ (Clinical research ed.). 10/2005; 331(7517):634; discussion 636; author reply 636-7.

• Assessing occupational and domestic ELF magnetic field exposure in the uk adult brain tumour study: results of a feasibility study.

  Authors: Martie van Tongeren, Terry Mee, Pamela Whatmough, Lisa Broad, Myron Maslanyj, Stuart Allen, Ken Muir, Patricia McKinney

  Radiation protection dosimetry. 02/2004; 108(3):227-36.

  The feasibility of measuring exposure to extremely low frequency magnetic fields (ELF MF) in the UK Adult Brain Tumour Study (UKABTS) was examined. During the study, 81 individuals and 30 companiesThe feasibility of measuring exposure to extremely low frequency magnetic fields (ELF MF) in the UK Adult Brain Tumour Study (UKABTS) was examined. During the study, 81 individuals and 30 companies were approached with 79 individuals and 25 companies agreeing to participate. Exposure data were collected using EMDEX II dosemeters worn by the participants for 3-4 consecutive days. Data were collected over a total of 321 d, including non-occupational periods. The results showed occupational exposure to be the main determinant of overall exposure. Moderate to strong correlations were found between arithmetic mean exposure and all other metrics with the possible exception of maximum exposure. Significant differences in exposure were found between job categories with large variability in certain categories. Highest average exposures were found for security officers (arithmetic mean, AM: 0.78 micro T), secretaries (AM: 0.48 micro T) and dentists (AM: 0.42 micro T). Welding and working near high-voltage power lines were associated with elevated exposure. In summary, acceptably precise measures of ELF MF exposure are feasible at relatively moderate cost. The results were used to develop a protocol for data collection from subjects in the UKABTS.