Michael F G Murphy

Newcastle University, Newcastle upon Tyne, ENG, United Kingdom

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Publications (36)249.17 Total impact

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    ABSTRACT: To assess recruitment of children to national clinical trials for acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in Great Britain during 1980-2007 and describe variation by some factors that might influence trial entry. Records of leukaemia patients aged 0-14 years at diagnosis were identified in the National Registry of Childhood Tumours and linked to birth registrations, Children's Cancer and Leukaemia Group records, Hospital Episode Statistics and Medical Research Council clinical trial registers. Trial entry rates were compared between categories of birth weight, congenital malformation, socioeconomic status and ethnicity. 9147 ALL and 1466 AML patients were eligible for national clinical trials during 1980-2007. Overall recruitment rates were 81% and 60% respectively. For ALL, rates varied significantly with congenital malformation (Down syndrome 61%, other malformations 80%, none 82%; p<0.001) and ethnicity (South Asian 78%, other minority groups 80%, white 85%; p<0.001). For AML, rates varied with birth weight (< 2500 g 48%, 2500-4000 g 69%, >4000 g 67%; p=0.001) and congenital malformation (Down syndrome 28%, other malformations 56%, none 63%; p<0.001). Although recruitment rates to clinical trials for childhood leukaemia are high, future trials should monitor possible variation by birth weight, ethnicity and presence of congenital malformations.
    Archives of Disease in Childhood 03/2014; · 3.05 Impact Factor
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    ABSTRACT: Accurate population-based data are needed on the incidence of cancer in children born after assisted conception. We linked data on all children born in Britain between 1992 and 2008 after assisted conception without donor involvement with data from the United Kingdom National Registry of Childhood Tumours to determine the number of children in whom cancer developed before 15 years of age. Cohort cancer rates were compared with population-based rates in Britain over the same period, with stratification for potential mediating and moderating factors, including sex, age at diagnosis, birth weight, singleton versus multiple birth, parity, parental age, type of assisted conception, and cause of parental infertility. The cohort consisted of 106,013 children born after assisted conception (700,705 person-years of observation). The average duration of follow-up was 6.6 years. Overall, 108 cancers were identified, as compared with 109.7 expected cancers (standardized incidence ratio, 0.98; 95% confidence interval [CI], 0.81 to 1.19; P=0.87). Assisted conception was not associated with an increased risk of leukemia, neuroblastoma, retinoblastoma, central nervous system tumors, or renal or germ-cell tumors. It was associated with an increased risk of hepatoblastoma (standardized incidence ratio, 3.64; 95% CI, 1.34 to 7.93; P=0.02; absolute excess risk, 6.21 cases per 1 million person-years) and rhabdomyosarcoma (standardized incidence ratio, 2.62; 95% CI, 1.26 to 4.82; P=0.02; absolute excess risk, 8.82 cases per 1 million person-years), with hepatoblastoma developing in 6 children and rhabdomyosarcoma in 10 children. The excess risk of hepatoblastoma was associated with low birth weight. There was no increase in the overall risk of cancer among British children born after assisted conception during the 17-year study period. Increased risks of hepatoblastoma and rhabdomyosarcoma were detected, but the absolute risks were small. (Funded by Cancer Research UK and others.).
    New England Journal of Medicine 11/2013; 369(19):1819-27. · 51.66 Impact Factor
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    ABSTRACT: Tumours occurring in children differ considerably from those occurring at older ages but exhibit common features. Those occurring in the teenage/young adult (TYA) years represent a transitional mixture of child and adult tumours and pose a considerable challenge for optimal clinical management and service provision. Nevertheless the fundamental processes of malignant change, arising from genetic/epigenetic interaction with environmental exposures, seem to operate across all ages and the entire tumour spectrum. We focus here on the ways in which genotype (and epigenetic modification), growth processes (particularly in utero), and exposure to ionising radiation (in conjunction with genetic susceptibility) affect cancer risk from childhood to adulthood, whether as a primary occurrence, or a second primary tumour following earlier primary occurrence and treatment.
    Maturitas 07/2013; · 2.84 Impact Factor
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    ABSTRACT: Previously we identified space-time clustering in certain childhood cancers. The present study aimed to determine whether there was cross-space-time clustering between different diagnostic groups. A total of 32,295 cases were diagnosed during 1969-1993. Cross-space-time clustering was analysed by a second-order procedure based on Diggle's method. Locations were birth and diagnosis addresses. The following space-time combinations were examined: address and date of birth; address at birth and date of diagnosis; address and date of diagnosis. Cross-space-time clustering analyses considered clustering pairs of cases from two different diagnostic groups. Formal statistical significance was taken as P < 0.00067 and marginal significance 0.01 > P ≥ 0.00067. Based on address at birth and date of diagnosis there was statistically significant cross-clustering between cases of HL and intracranial and intraspinal embryonal tumours (IIET), both aged 0-14 years (P < 0.0001). Based on address and date of birth there was marginally significant cross-clustering between cases of lymphoid leukaemia (LL) aged 5-14 years and Hodgkin lymphoma (HL) aged 0-14 years (P = 0.0019). Based on address and date of diagnosis there was marginally significant cross-clustering between cases of LL aged 1-4 years and soft tissue sarcoma (STS) aged 0-14 years (P = 0.0041). Findings from this study are consistent with possible common aetiological factors between different diagnostic groups. They suggest a common aetiology for the following pairs of diagnostic groups: HL and IIET; older cases of LL and HL; younger cases of LL and soft tissue sarcoma. The possibility of common infectious mechanisms should be explored. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 06/2013; · 6.20 Impact Factor
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    ABSTRACT: Retinoblastoma (RB) is an important ocular malignancy of childhood. It has been commonly accepted for some time that knockout of the two alleles of the RB1 gene is the principal molecular target associated with the occurrence of RB. In this article, we examine the validity of the two-hit theory for RB by comparing the fit of a stochastic model with two or more mutational stages. Unlike many such models, our model assumes a fully stochastic stem cell compartment, which is crucial to its behavior. Models are fitted to a population-based dataset comprising 1,553 cases of RB for the period 1962–2000 in Great Britain (England, Scotland and Wales). The population incidence of RB is best described by a fully stochastic model with two stages, although models with a deterministic stem cell compartment yield equivalent fit; models with three or more stages fit much less well. The results strongly suggest that knockout of the two alleles of the RB1 gene is necessary and may be largely sufficient for the development of RB, in support of Knudson's two-hit hypothesis.
    International Journal of Cancer 01/2012; 130(3):631 - 640. · 6.20 Impact Factor
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    ABSTRACT: The α4β2 nicotinic receptor is of central importance in tobacco dependence, while the homomeric α7 receptor may also play a role. In this candidate gene study, we examine the association between 8 single nucleotide polymorphisms (SNPs) in genes coding for nicotinic acetylcholine receptor subunits α4 (rs1044396, rs2273504, rs2236196, and rs2273502), α7 (rs2133965 and rs4779969), and β2 (rs2072660 and rs2072661) and smoking abstinence in a cohort of quitters enrolled in a clinical trial of behavioral support. Data were obtained from the "Patch in Practice" study, involving 925 smokers in the United Kingdom. All participants were given an 8-week course of 15 mg of transdermal nicotine replacement therapy and blood was taken for genotyping. Logistic regression analyses assessed the association between each selected SNP and smoking abstinence at 4, 12, 26, and 52 weeks. There were no statistically significant associations with smoking cessation success or nicotine intake assessed by plasma cotinine levels. However, rs2273502 was associated with a consistent (though nonsignificant) increase in the odds of abstinence. Conclusions: There was no compelling evidence that these SNPs were associated with a reduced or higher chance of abstinence. However, rs2273502 may be worth investigating in future studies.
    Nicotine & Tobacco Research 12/2011; 14(8):993-7. · 2.48 Impact Factor
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    ABSTRACT: The rs1051730 genetic variant within the CHRNA5-A3-B4 gene cluster is associated with heaviness of smoking and has recently been reported to be associated with likelihood of stopping smoking. We investigated the potential association of rs1051730 genotype with reduced likelihood of smoking cessation in 2 cohorts of treatment-seeking smokers in primary care in the United Kingdom. Data were drawn from 2 clinical trials on which DNA was available. One sample was a randomized placebo-controlled trial of nicotine transdermal patch and the other sample an open-label trial where all participants received nicotine transdermal patch. Smoking status was biochemically verified. Logistic regression was used to assess evidence for association in each sample, and data were combined within a meta-analysis. There was evidence of association of rs1051730 genotype with short-term (4-week) cessation in our open-label trial sample but not our placebo-controlled trial sample. When combined in a meta-analysis, this effect remained. There was no evidence of association at later follow-up intervals. Adjustment for cigarette consumption and tobacco dependence did not alter these results substantially. Our data, taken together with previous recent studies, provide some support for a weak association between this variant and short-term smoking cessation in treatment-seeking smokers, which does not seem to operate only among those receiving nicotine replacement therapy. Moreover, the rs1051730 variant may not merely operate as a marker for dependence or heaviness of smoking.
    Nicotine & Tobacco Research 06/2011; 13(10):982-8. · 2.48 Impact Factor
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    ABSTRACT: High birth weight increases the risk of childhood acute lymphoid leukemia (ALL) through unknown mechanisms. Whether this risk is specific to ALL subtypes is unknown, and low case numbers have prevented investigation of the rarer leukemias. Here we address these associations using a large population-based dataset. Using the National Registry of Childhood Tumors, birth weights of 7,826 leukemia cases, defined by immunophenotype and cytogenetic subgroup, were compared with those of 10,785 controls born in England and Wales between 1980 and 2007. The risk for overall leukemia increases 7% with each 0.5 kg increase in birth weight (OR 1.07, 95%CI 1.04-1.10). This risk is limited to the lymphoid leukemias (OR 1.08, 95%CI 1.05-1.12) diagnosed between 1 and 9 years of age. Analysis by cytogenetic feature reveals that there appears to be association with specific chromosomal abnormality: the risk of tumors with high hyperdiploid karyotypes increases 12% per 0.5 kg increase in birth weight (OR 1.12, 95%CI 1.05-1.20), and t(1;19) tumors show an increased risk of 41% per 0.5 kg increase (OR 1.41, 95%CI 1.09-1.84). The risk of acute myeloid leukemia is elevated in high and low birth weight babies. There is no significant risk relationship to other leukemias or myeloproliferative diseases. Birth weight is a risk factor for ALL and AML. Other subtypes of the disease are not significantly affected. There appears to be association with specific chromosomal abnormality, which may aid our understanding of the development of childhood leukemia in utero.
    Pediatric Blood & Cancer 06/2011; 58(1):7-11. · 2.35 Impact Factor
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    ABSTRACT: To describe patterns of hospital care and to evaluate factors influencing place of death for children who died after a diagnosis of cancer in England during 1999-2006. Registrations of children on the National Registry of Childhood Tumours (NRCT) who were diagnosed with cancer and died during 1999-2006 in England were linked to the Hospital Episode Statistics (HES) and to death certificates. Multivariable logistic modelling was used to assess factors that influence dying at home or in hospital. 1864 (96%) of children with cancer registrations were linked to HES records. The validation of hospital as a place of death and ethnicity between data sources was good, although anomalies within HES data exist. Similar proportions of children are dying at home (45%) and in hospital (47%), and the percentage dying in a hospice or care home increased from 2% to 10%. Of the children who died in hospital, 74% were admitted as emergencies or as a transfer from another hospital. Greater proportions of children were diagnosed with a leukaemia or lymphoma, those dying within six months of diagnosis, Asian and Black children, those from a deprived background and those not treated in a CCLG centre died in a hospital. Patterns of hospital care varied considerably by type of cancer, death within six months of diagnosis, ethnicity and deprivation. Further research is required to elucidate explanations for these patterns and to evaluate methods to increase the proportion of children dying at home who wish to do so.
    European journal of cancer (Oxford, England: 1990) 04/2011; 47(14):2175-81. · 4.12 Impact Factor
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    ABSTRACT: Cigarette smoking remains the leading cause of preventable death worldwide. However, the efficacy of available first-line therapies remains low, particularly in primary care practice where most smokers seek and receive treatment. These observations reinforce the notion that 'one size fits all' smoking cessation therapies may not be optimal. Therefore, a translational research effort was launched by the Imperial Cancer Research Fund (later Cancer Research UK) General Practice Research Group, who led a decade-long research enterprise that examined the influence of pharmacological hypothesis-driven research into genetic influences on drug response for smoking cessation with transdermal nicotine replacement therapy in general practice. New and previously published smoking cessation genetic association results of 30 candidate gene polymorphisms genotyped for participants in two transdermal nicotine replacement clinical trials based in UK general practices, which employed an intention to analyze approach. By this high bar, one of the polymorphisms (COMT rs4680) was robust to correction for multiple comparisons. Moreover, future research directions are outlined; and lessons learned as well as best-practice models for designing, analyzing, and translating results into clinical practice are proposed. The results and lessons learned from this general practice-based pharmacogenetic research programme provide transportable insights at the transition to the second generation of pharmacogenetic and genomic investigations of smoking cessation and its translation to primary care.
    Nicotine & Tobacco Research 01/2011; 13(3):157-67. · 2.48 Impact Factor
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    Richard Wakeford, Sarah C Darby, Michael F G Murphy
    Biophysik 05/2010; · 1.70 Impact Factor
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    Richard Wakeford, Sarah C Darby, Michael F G Murphy
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    ABSTRACT: Notably raised rates of childhood leukaemia incidence have been found near some nuclear installations, in particular Sellafield and Dounreay in the United Kingdom, but risk assessments have concluded that the radiation doses estimated to have been received by children or in utero as a result of operations at these installations are much too small to account for the reported increases in incidence. This has led to speculation that the risk of childhood leukaemia arising from internal exposure to radiation following the intake of radioactive material released from nuclear facilities has been substantially underestimated. The radionuclides discharged from many nuclear installations are similar to those released into the global environment by atmospheric nuclear weapons testing, which was at its height in the late-1950s and early-1960s. Measurements of anthropogenic radionuclides in members of the general public resident in the vicinity of Sellafield and Dounreay have found levels that do not differ greatly from those in persons living remote from nuclear installations that are due to ubiquitous exposure to the radioactive debris of nuclear weapons testing. Therefore, if the leukaemia risk to children resulting from deposition within the body of radioactive material discharged from nuclear facilities has been grossly underestimated, then a pronounced excess of childhood leukaemia would have been expected as a consequence of the short period of intense atmospheric weapons testing. We have examined childhood leukaemia incidence in 11 large-scale cancer registries in three continents for which data were available at least as early as 1962. We found no evidence of a wave of excess cases corresponding to the peak of radioactive fallout from atmospheric weapons testing. The absence of a discernible increase in the incidence of childhood leukaemia following the period of maximum exposure to the radioactive debris of this testing weighs heavily against the suggestion that conventional methods are seriously in error when assessing the risk of childhood leukaemia from exposure to man-made radionuclides released from nuclear installations.
    Biophysik 03/2010; 49(2):213-27. · 1.70 Impact Factor
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    ABSTRACT: A combined cohort of 8,884 North American, 2,893 British and 1,574 Nordic subjects with Wilms tumor (WT) diagnosed before 15 years of age during 1960-2004 was established to determine the risk of secondary malignant neoplasms (SMN). After 169,641 person-years (PY) of observation through 2005, 174 solid tumors (exclusive of basal cell carcinomas) and 28 leukemias were ascertained in 195 subjects. Median survival time after a solid SMN diagnosis 5 years or more from WT was 11 years; it was 10 months for all leukemia. Age-specific incidence of secondary solid tumors increased from approximately 1 case per 1,000 PY at age 15 to 5 cases per 1,000 PY at age 40. The cumulative incidence of solid tumors at age 40 for subjects who survived free of SMNs to age 15 was 6.7%. Leukemia risk, by contrast, was highest during the first 5 years after WT diagnosis. Standardized incidence ratios (SIRs) for solid tumors and leukemias were 5.1 and 5.0, respectively. Results for solid tumors for the 3 geographic areas were remarkably consistent; statistical tests for differences in incidence rates and SIRs were all negative. Age-specific incidence rates and SIRs for solid tumors were lower for patients whose WT was diagnosed after 1980, although the trends with decade of diagnosis were not statistically significant. Incidence rates and SIRs for leukemia were highest among those diagnosed after 1990 (p-trend = 0.003). These trends may reflect the decreasing use of radiation therapy and increasing intensity of chemotherapy in modern protocols for treatment of WT.
    International Journal of Cancer 11/2009; 127(3):657-66. · 6.20 Impact Factor
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    ABSTRACT: We previously reported evidence that the T allele of the dopamine type-2 receptor (DRD2) rs1800497 polymorphism is associated with improved response to nicotine replacement therapy (NRT) relative to placebo and that this association may only be present in females. However, evidence of the poor replication validity of genetic association studies is growing, particularly among those that report subgroup analyses. We therefore attempted to replicate our previous finding of an association between the DRD2 rs1800497 genotype and response to NRT in a new, larger cohort, with greater statistical power. Participants were randomly assigned to one of two levels of smoking cessation behavioral support (usual care vs. weekly support). All participants received 8 weeks of 15-mg NRT transdermal patch. The presence of one or more T alleles was associated with a slightly but not significantly lower likelihood of abstinence at 3 and 6 months. We found evidence of a genotype x sex interaction effect. However, stratified analyses indicated a main effect of genotype opposite to the effect reported previously, with females carrying one or more copies of the T allele less likely to be abstinent. Our results do not support an association between the DRD2 rs1800497 (Taq1A) polymorphism and response to NRT, contrary to our previous study.
    Nicotine & Tobacco Research 04/2009; 11(4):404-7. · 2.48 Impact Factor
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    ABSTRACT: Previously, we identified space-time clustering in certain childhood cancers around diagnosis residence. These findings provided support for the involvement of environmental agents in etiological processes occurring close to diagnosis. We have reanalyzed the same British population-based dataset. The aim of the study was to determine whether there was space-time clustering around the residence at birth in relation to time of birth and separately from time of diagnosis. A total of 29,553 cases, diagnosed during the period 1969-1993, were examined by a second-order procedure based on K-functions. Locations were birth addresses, but separately, both dates of birth and diagnosis were analyzed. There was statistically significant space-time clustering for Hodgkin lymphoma (HL) and central nervous system (CNS) tumors (p=0.047 and 0.01, respectively, based on birth date) and for total leukemia at ages 1-4 years only, Non-Hodgkin lymphoma (NHL) and Wilms tumor (p=0.01, 0.02 and 0.006, respectively, based on diagnosis date). These results, interpreted together with other epidemiological evidence, suggest an etiological role for environmental factors focused around birth address for certain childhood cancers. For HL and CNS tumors, findings suggest that etiological exposures occurred at similar ages or in utero. For leukemia, NHL and Wilms tumor there is support for exposures occurring at similar times before diagnosis. For leukemia, HL, NHL and CNS tumors, but not Wilms tumor, the findings are consistent with infectious hypotheses.
    International Journal of Cancer 11/2008; 124(2):449-55. · 6.20 Impact Factor
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    ABSTRACT: The aetiology of childhood cancer is poorly understood. Both genetic and environmental factors are likely to be involved. The presence of spatial clustering is indicative of a very localized environmental component to aetiology. Spatial clustering is present when there are a small number of areas with greatly increased incidence or a large number of areas with moderately increased incidence. To determine whether localized environmental factors may play a part in childhood cancer aetiology, we analyzed for spatial clustering using a large set of national population-based data from Great Britain diagnosed 1969-1993. The Potthoff-Whittinghill method was used to test for extra-Poisson variation (EPV). Thirty-two thousand three hundred and twenty-three cases were allocated to 10,444 wards using diagnosis addresses. Analyses showed statistically significant evidence of clustering for acute lymphoblastic leukaemia (ALL) over the whole age range (estimate of EPV = 0.05, p = 0.002) and for ages 1-4 years (estimate of EPV = 0.03, p = 0.015). Soft-tissue sarcoma (estimate of EPV = 0.03, p = 0.04) and Wilms tumours (estimate of EPV = 0.04, p = 0.007) also showed significant clustering. Clustering tended to persist across different time periods for cases of ALL (estimate of between-time period EPV = 0.04, p =0.003). In conclusion, we observed low level spatial clustering that is attributable to a limited number of cases. This suggests that environmental factors, which in some locations display localized clustering, may be important aetiological agents in these diseases. For ALL and soft tissue sarcoma, but not Wilms tumour, common infectious agents may be likely candidates.
    International Journal of Cancer 10/2008; 124(4):932-6. · 6.20 Impact Factor
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    ABSTRACT: Several studies have shown serum urate to be an independent risk factor for vascular disease, but others have not, although a stronger association in women than in men has been a consistent finding. Studies of stroke patients have shown possible associations between urate level and stroke severity, but there have been no large cohort studies of the effect of urate on the long-term risk of future vascular events in patients with a transient ischaemic attack (TIA) or stroke. We studied this relationship in 2 independent cohorts. Individual data on 15,483 patient-years of follow-up from the UK-TIA trial (13,182 patient-years) and the Oxford TIA study (2,301 patient-years) were analyzed. Hazard ratios (per unit increase of baseline urate in mg/dl) for the risks of stroke and acute coronary events (ACE) were obtained from Cox models stratified by study, with and without adjustment for potential confounders. Potential interactions between urate and baseline characteristics were also assessed. Linear associations between urate and risk of ACE were found in both studies: pooled age- and sex-adjusted hazard ratio = 1.17, 95% CI 1.06-1.30, per unit increase of urate (p = 0.003). Sex, body mass index and previous myocardial infarction or angina were effect modifiers, but only the effect of sex remained after adjustment for other risk factors (p = 0.002), with a 5th:1st quintile hazard ratio of 4.23 (1.97-9.07, p < 0.0001) in women and 1.09 (0.70-1.71, p = 0.69) in men. These findings were consistent across the 2 studies. No associations were found between urate level and either risk or severity of stroke. High urate levels were independent predictors of long-term risk of ACE in women who had a TIA or stroke, but not in men, in 2 independent studies. Urate levels could be useful in identifying women at high risk of coronary events in routine practice.
    Cerebrovascular Diseases 09/2008; 26(5):517-24. · 2.81 Impact Factor
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    ABSTRACT: The serotonin pathway has been implicated in nicotine dependence and may influence smoking cessation. Therefore, 792 cigarette smokers from the Patch in Practice trial were genotyped for the tryptophan hydroxylase (TPH1 A779C), serotonin transporter (SLC6A45-HTTLPR), and 5-HT1A (HTR1A C-1019G) polymorphisms. Cox regression analysis did not demonstrate significant effects of any of the three genotypes on relapse to smoking: TPH1 (Reference AA; AC: hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.78, 1.24, p=0.90; CC: HR 0.93, 95% CI 0.73, 1.18, p=0.55); 5-HTTLPR (Reference LL; SL: HR 1.01, 95% CI 0.85, 1.20, p=0.90; SS: HR 1.13, 95% CI 0.91, 1.39, p=0.27); HTR1A (Reference CC; CG: HR 1.04, 95% CI 0.86, 1.25, p=0.70; GG: HR 1.01, 95% CI 0.82, 1.24, p=0.93). Moreover, pooled analyses of data from all three extant pharmacogenetic NRT trials (N=1398) found no significant effect of 5-HTTLPR genotype on continuous abstinence at 12-week (Reference LL; SL: odds ratio (OR)=1.25, 95% CI 0.89, 1.74, p=0.19; SS: OR=1.31, 95% CI 0.86, 1.98, p=0.21) or 26-week follow-up (Reference LL; SL: OR=0.93, 95% CI 0.64, 1.33, p=0.68; SS: OR=1.00, 95% CI 0.63, 1.58, p=1.00). These data do not support a statistically or clinically significant moderating effect of these specific 5-HT pathway genetic variants on smoking cessation. However, the possibility remains that other variants in these or other 5-HT genes may influence NRT efficacy for smoking cessation in treatment seeking smokers.
    Drug and Alcohol Dependence 07/2008; 98(1-2):77-85. · 3.14 Impact Factor
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    ABSTRACT: We attempted to extend a previous finding of an association of COMT genotype with response to nicotine-replacement therapy (NRT), in a larger cohort of treatment-seeking smokers, with greater statistical power to detect possible moderating effects of sex. We also investigated the association of the COMT genotype with withdrawal and mood symptoms, to identify possible mediating mechanisms by which the COMT genotype might influence response to NRT. Participants were eligible if they were aged 18 years or older, and if they smoked 10 cigarettes per day or more; they were recruited from 26 general practice clinics in Buckinghamshire and Oxfordshire in the United Kingdom. All participants received 8 weeks of 15-mg NRT transdermal patch. Confirmation of abstinence was defined as an exhaled CO of less than 10 parts per million (ppm), or salivary cotinine concentration of less than 15 ng/ml. Cox regression analysis indicated a significant effect of the COMT genotype on relapse into smoking (P=0.001), with shorter times to relapse being observed among the AG (Val/Met) and GG (Val/Val) genotype groups. These effects were observed both during active treatment and as soon as active treatment had ended. The effect, however, was greater, once active treatment had ended, in the subgroup of smokers who had abstained up to this point. We did not observe any evidence of a sex difference in the effect of the COMT genotype. These effects did not seem to be mediated by self-reported withdrawal or mood symptoms. Our results indicate that the COMT genotype is associated with the likelihood of smoking cessation in smokers treated with the NRT transdermal patch. Future large-scale studies will be required to afford sufficient power to simultaneously investigate the role of multiple genetic variants in treatment responses, and the effects of potential moderating variables on these associations.
    Pharmacogenetics and Genomics 03/2008; 18(2):121-8. · 3.61 Impact Factor

Publication Stats

364 Citations
249.17 Total Impact Points

Institutions

  • 2008–2013
    • Newcastle University
      • Institute of Health and Society
      Newcastle upon Tyne, ENG, United Kingdom
    • Alpert Medical School - Brown University
      • Department of Family Medicine
      Providence, RI, United States
  • 2005–2013
    • University of Oxford
      • • Childhood Cancer Research Group (CCRG)
      • • Nuffield Department of Clinical Medicine
      • • Department of Paediatrics
      Oxford, England, United Kingdom
  • 2011
    • Stanford Medicine
      Stanford, California, United States
  • 2006–2011
    • University of Bristol
      • School of Experimental Psychology
      Bristol, ENG, United Kingdom
  • 2010
    • The University of Manchester
      Manchester, England, United Kingdom
  • 2007
    • Temple University
      • Department of Public Health
      Philadelphia, PA, United States
    • Brown University
      • Department of Medicine
      Providence, RI, United States