From: Subject: Mobile phone use and risk of glioma in adults: case-control study -- Hepworth et al. 332 (7546): 883 -- BMJ Date: Tue, 16 May 2006 08:29:06 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0021_01C678C2.CC08B8B0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_0021_01C678C2.CC08B8B0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://bmj.bmjjournals.com/cgi/content/full/332/7546/883 Mobile phone use and risk of glioma in adults: = case-control study -- Hepworth et al. 332 (7546): 883 -- BMJ
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BMJ  2006;332:883-887 (15 April),=20 doi:10.1136/bmj.38720.687975.55 (published 20 January 2006) =
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Research

Mobile phone use and risk of glioma in adults: case-control = study=20

Sarah J Hepworth, medical=20 statistician1, Minouk J=20 Schoemaker, medical=20 statistician2, Kenneth R=20 Muir, professor of=20 epidemiology3, Anthony J=20 Swerdlow, professor of=20 epidemiology2, Martie J A = van=20 Tongeren, senior lecturer in occupational and = environmental=20 health4, Patricia A=20 McKinney, professor of paediatric=20 epidemiology1=20

1 Centre for Epidemiology and = Biostatistics,=20 Leeds Institute of Genetics, Health, and Therapeutics (LIGHT), = Leeds LS2=20 9LN, 2 Institute of Cancer Research, Section of = Epidemiology,=20 Sutton, Surrey SM2 5NG, 3 Division of Epidemiology and = Public=20 Health, School of Community Health Sciences, Queen's Medical = Centre,=20 Nottingham NG7 2UH, 4 Centre for Occupational and = Environmental=20 Health, Division of Epidemiology and Health Sciences, University = of=20 Manchester, Manchester M13 9PL

Correspondence to: P A McKinney p.a.mckinney{at}leeds.ac.uk

Abstract

Objective To investigate the risk of glioma in adults in = relation to mobile phone use.

Design Population based case-control study with = collection=20 of personal interview data.

Setting Five areas of the United Kingdom.

Participants 966 people aged 18 to 69 years diagnosed = with=20 a glioma from 1 December 2000 to 29 February 2004 and = 1716=20 controls randomly selected from general practitioner=20 lists.

Main outcome measures Odds ratios for risk of glioma in=20 relation to mobile phone use.

Results The overall odds ratio for regular phone use was = 0.94 (95% confidence interval 0.78 to 1.13). There was = no=20 relation for risk of glioma and time since first use, = lifetime=20 years of use, and cumulative number of calls and hours = of use.=20 A significant excess risk for reported phone use = ipsilateral to=20 the tumour (1.24, 1.02 to 1.52) was paralleled by a = significant=20 reduction in risk (0.75, 0.61 to 0.93) for = contralateral=20 use.

Conclusions Use of a mobile phone, either in the short = or=20 medium term, is not associated with an increased risk = of=20 glioma. This is consistent with most but not all = published=20 studies. The complementary positive and negative risks=20 associated with ipsilateral and contralateral use of = the phone=20 in relation to the side of the tumour might be due to = recall=20 bias.

Introduction

Gliomas are the most common malignancy of the central = nervous=20 system in adults, and the prognosis is extremely = poor.1<= /A>=20 The distinct histopathology and cellular origin of = gliomas are=20 probably associated with different aetiological = pathways and=20 mechanisms of carcinogenesis than other subtypes of = brain=20 tumours; the aetiology of gliomas, however, remains = unclear.=20 Recently, considerable interest has focused on whether = the use=20 of mobile phones is associated with an increased risk = of=20 gliomas and other brain tumours, even though little is = known=20 about potential mechanisms.2<= /A>=20 The energy of the radiofrequency fields emitted by mobile=20 phones is thought to be insufficient to cause malignant = transformation through direct damage to DNA.3<= /A>=20

Most published epidemiological studies on mobile phone use = and=20 gliomas have not generally reported any increased risk = either=20 overall or with long term use.4<= /A>-7<= /A>=20 Individual studies have found positive associations = between=20 high grade astrocytoma (glioma) and phone use = ipsilateral to=20 the side of the tumour,8<= /A>=20 brain tumours and phone use in rural areas,9<= /A>=20 and use of analogue mobile phones.8<= /A>=20 1= 0=20

We carried out a large population based case-control study = of=20 966 patients with glioma in the United Kingdom. This study = is=20 part of the Interphone project,1= 1=20 an international collaboration of 13 countries = investigating=20 mobile phone use and the risk of intracranial = tumours.=20

Methods and=20 participants

The study took place in the Thames regions of south east = England=20 and four areas to the north (Trent, West Midlands, West=20 Yorkshire, and southern Scotland). The total catchment=20 population (28.4 million) comprised 48.3% of the UK = population.=20 All areas followed a common protocol, with identical = methods of=20 case ascertainment and data collection with controls = randomly=20 sampled from general practitioner lists. The south east = slightly differed in its method of control selection = and the=20 age range covered.

Cases were ascertained from multiple sources, including = hospital=20 departments (neurosurgery, neuro-oncology, neuropathology,=20 neuroradiology, neurology) and cancer registries. = Patients aged=20 18-69 years (northern centres) or 18-59 years (south = east)=20 lived in the study areas and had a first diagnosis = between 1=20 December 2000 and 30 June 2003 (northern) or 29 = February 2004=20 (south east) with a glioma (ICD-O-3 (international=20 classification of diseases for oncology)1= 2=20 topography: C71, morphology: 9380-9411, 9420-9460, = 9480, 9505).=20 Data on site, laterality (left, right, central) and = grade of=20 tumour (WHO grade high III-IV; low I-II1= 3)=20 were abstracted from scan and pathology reports. =

In the most recent year we have published data for (1992) = an=20 estimated 98% of the UK population was registered with a=20 general practitioner.1= 4=20 Controls were randomly selected from general = practitioners'=20 lists by a preset algorithm. In the south east the = controls=20 were frequency matched to reflect the age, sex, and=20 geographical distribution of cases. In the northern centres = one=20 control per case was individually matched on age, sex, and=20 general practice after the patient with glioma was = interviewed.=20 Nonparticipating controls were replaced. Parallel = case-control=20 studies of meningioma, acoustic neuroma, and other brain=20 tumours were carried out with identical methods and=20 questionnaires; the controls for these cases were = included in=20 the present analyses.

Consultants or general practitioners approached eligible=20 participants personally or by an invitation letter. The = study=20 was introduced as an investigation of risk factors for = brain=20 tumours, without emphasising mobile phones. With the=20 participant's informed consent, trained interviewers = conducted=20 a computer assisted personal interview. For 69 patients = with=20 glioma (7%), interviewers conducted proxy interviews, = mainly=20 with spouses.

During the interview, if participants reported that they = had=20 ever made one or more calls each week on average for a = period=20 of six months or longer, they were asked a detailed set of=20 questions on mobile phone use. For such participants, = all makes=20 and models of phone were recorded, with a comprehensive = repertoire of photographs to prompt recall. For each = phone, the=20 interviewer recorded the network operator, start and = stop year,=20 and the number and duration of calls made and received. = If=20 participants were uncertain about the calendar years or = amount=20 of use, a range was reported with the mean value taken = for=20 analysis. Additional details were gathered on which = side of the=20 head the phone was mostly used (50% or more of the = time) and=20 factors influencing emitted power levels to the head, = including=20 use of hands-free kits (start and stop dates of use and = proportion of time used) and whether the phone was used = mainly=20 in an urban or rural area or equally in both.1= 5=20

In the analysis, we defined regular phone use as use for = at=20 least six months in the period more than a year before=20 diagnosis. We defined diagnostic date as the date of = diagnostic=20 pathology (n =3D 935, 97%) or date of the first = diagnostic scan=20 (n =3D 31, 3%) if diagnostic pathology was unavailable. = We=20 assessed exposure to mobile phones using the number of = years=20 from first regular use of a phone until diagnosis or = equivalent=20 reference date for controls, lifetime years of regular = use,=20 lifetime cumulative use (hours), and lifetime = cumulative number=20 of calls. Long term users (> 10 years) were = dichotomised=20 into heavy (3<= /A>=20 113 hours) and light (< 113 hours) cumulative hours = of use=20 in the period 10 or more years before diagnosis, with = the cut=20 off point based on the median hours of use among = control=20 participants. We used data collated by = Interphone1= 1=20 to classify phones as either analogue or digital, based = on make=20 and model of phone, year of use, and network operator=20 capabilities during that period.

The exposure period for people with glioma was calculated = up=20 to a year before the date of diagnosis. An equivalent = reference=20 date was required for control participants that allowed = for=20 the increase in mobile phone use over the study period and = as=20 controls tended to be interviewed after the patients with=20 glioma. For each area (south east, northern), we = constructed=20 case strata by single calendar year of interview and = single=20 year interval between diagnosis and interview = ("interview lag=20 time"). Control participants interviewed in each = calendar year=20 were randomly allocated to strata of interview lag = time,=20 proportionally to the distribution of the cases in the = same=20 calendar year, to obtain a similar distribution of lag = time as=20 in the cases. We then calculated the reference dates = for=20 controls by subtracting the mean interview lag time in = cases in=20 that stratum from the interview dates of the controls. = Exposure=20 indices were calculated up to a year before this = reference date=20 for controls (that is, a one year latency time was = used).=20 Additional analyses were carried out with a five year = latency=20 time.

Statistical analysis
For statistical = analysis we=20 used unconditional logistic regression (StataCorp, = College=20 Station, TX) adjusted for nine regions (five regions = within the=20 south east and the four northern regions), age at = reference=20 date (five year categories), sex, deprivation (Townsend = score1= 6),=20 and combinations of interview year and lag time to = account for=20 the fact that controls were, on average, interviewed = later in=20 the study period than patients with glioma. We derived = odds=20 ratios for cumulative use with and without modification = for=20 reported use of headsets or hands-free sets in a vehicle, = or=20 both,7<= /A>=20 1= 7=20 with and without proxy case interviews, and separately = for high=20 and low grade tumours and urban versus rural use. We = also=20 performed a conditional logistic regression analysis on = the=20 matched northern case-control dataset.

We used two methods to assess the risk of a tumour = ipsilateral=20 or contralateral to side of phone use. Firstly, we took = two=20 groups of patients with right and left sided tumours1= 7=20 and randomly assigned controls to each group and = considered=20 them to have a tumour on that side (50% left, 50% = right) for=20 the analysis. The odds ratio for risk of an ipsilateral = tumour=20 was based on the results of a logistic regression = analysis=20 where ipsilateral phone use was use on the same side of = the=20 head as the tumour for cases or the assigned side for = controls.=20 We adjusted the analysis for the side of the tumour as = well as=20 the variables adjusted for in the main analysis. If the = phone=20 was used on the opposite side to the side of = tumour/allocated=20 side the participant was classified as unexposed. Those = who=20 reported using the phone on both sides of the head were = considered exposed on both the left and right = sides.6<= /A>=20 1= 7=20 As the allocation of controls was based on a random = assignment,=20 the logistic regression analysis was repeated 500 = times; the=20 results for the analysis that gave the median odds = ratio for=20 ipsilateral regular phone use are presented. A similar = analysis=20 of contralateral use (use on the opposite side of the = head to=20 the tumour or allocated side) was performed. The second = method=20 calculates a relative risk for laterality of reported = side of=20 use in relation to tumour laterality but only in = cases.4<= /A>=20

Results

Researchers interviewed 966 cases (367 in the south east = and=20 599 in northern areas) and 1716 controls (630 and 1086). = The=20 main reasons for non-participation were the participant = was=20 too ill or had died before interview (cases 30%, controls = <=20 1%), nonresponse (cases 2%, controls 21%), refusal (cases = 10%,=20 controls 29%), and other reasons (refusal by consultant or=20 general practitioner, non-English speaking, mental = impairment)=20 (cases 7%, controls 5%). Non-responders included those = for whom=20 contact details may have been incorrect. Overall = response rates=20 were 51% for patients with glioma and 45% for controls, = representing the proportion of all eligible cases and = controls=20 from the study areas who were interviewed in the study. = Exclusion of the non-responders (that is, who may never = actually have been asked) gave response rates of 51% = and 57%.=20 Interviewed patients with glioma were broadly = representative of=20 the overall set of those eligible by age and sex but = differed=20 by deprivation category, being significantly more = affluent=20 (3D{chi}2 test for trend, P < 0.001). People = with=20 low grade glioma were significantly more likely to be=20 interviewed (3D{chi}=202 test,=20 P < 0.001) than those with high grade glioma. For = control=20 participants, those interviewed were more likely to be = women=20 (3D{chi}2 test, P < 0.001) and more likely to be=20 affluent (3D{chi}=202 test=20 for trend, P < 0.001) than those who were not interviewed. =

Ta= ble=20 1 shows the demographic distribution of interviewed cases = and controls. The proportion of men was higher among the=20 patients with glioma than in the control group. There = was also=20 a slight tendency for interviewed controls to live in = more=20 affluent areas than interviewed patients with = glioma.=20


View this=20 table:
[i= n=20 this window]
[in a new window]
  = 		Table 1 Demographic = distributions in cases and controls. Figures are = numbers=20 (percentages) of participants =

 = ;

Ta= ble=20 2 shows an odds ratio of 0.94 (95% confidence interval = 0.78=20 to 1.13) for regular phone users compared with those who = never=20 or only occasionally used mobile phones. There was no=20 association of risk with lifetime years of use, cumulative=20 hours of use, cumulative numbers of calls, nor = cumulative hours=20 of use over 10 years before the reference date. These=20 findings were similar after we excluded patients with = glioma=20 with proxy interviews (n =3D 69), adjusted cumulative = hours of=20 phone use and number of calls for use of hands-free = kits,=20 applied a five year lag time, or restricted analysis to = matched=20 case-control analysis of northern cases. Ta= ble=20 2 also shows no significant associations with use = in urban=20 or rural areas or separately for 650 high grade and 306 = low=20 grade gliomas.


View this=20 table:
[i= n=20 this window]
[in a new window]
  = 		Table 2 Odds ratios = and 95%=20 confidence intervals for risk of glioma in relation to = mobile=20 phone exposure*. Figures are numbers = (percentages)=20 of participants =

 = ;

We found a significant odds ratio of 1.24 (1.02 to 1.52) = for=20 a tumour ipsilateral to side of phone use and a reduced = odds=20 ratio for contralateral use (0.75, 0.61 to 0.93) (ta= ble=20 2). Similar respective excesses and deficits were = present=20 for all exposure measures of mobile phone use, = including use=20 for 3<= /A>=20 10 years (ipsilateral 1.60, 0.92 to 2.76; contralateral = 0.78,=20 0.43 to 1.41). To investigate this further, we analysed = regular=20 use ipsilateral and contralateral to handedness, which = gave=20 odds ratios of 0.78 (0.62 to 0.99) and 1.07 (0.85 to = 1.35),=20 respectively. The concordance between reported side of = use and=20 handedness was 59% for cases and 64% among controls. = The method=20 of Inskip et al4<= /A>=20 gave an overall relative risk of 1.3 (Fisher's exact P = <=20 0.001) for a tumour ipsilateral to the side of phone = use.=20

We examined use of analogue phones separately but there = were=20 no significant odds ratios with any exposure metric (ta= ble=20 3). Results from the conditional regression = analysis of=20 matched data from the northern centres did not differ = from the=20 overall findings.


View this=20 table:
[i= n=20 this window]
[in a new window]
  = 		Table 3 Odds ratios = and 95%=20 confidence intervals for risk of glioma in relation to = use of=20 analogue phones =

 = ;

Discussion

This large study on associations between mobile phone use = and=20 the risk of developing a glioma in a UK population has = nearly=20 twice as many cases as the largest previously reported = studies=20 of gliomas,4<= /A>=20 5<= /A>=20 with more long term users. In addition, it was designed = specifically to address exposure to mobile phones, with = comprehensive and relevant collection of data. Overall, = we=20 found no raised risk of glioma associated with regular mobile = phone use and no association with time since first use,=20 lifetime years of use, cumulative hours of use, or = number of=20 calls. Our results are consistent with findings from=20 investigations of mobile phone use in the US,4<= /A>=20 5<= /A>=20 Denmark,7<= /A>=20 1= 8=20 and Sweden,6<= /A>=20 though some studies have found isolated positive = associations=20 for particular variables.8<= /A>-1= 0=20

Analogue phones emit higher average power levels than = digital=20 phones.1= 9=20 If mobile phone use was causally linked to the development = of=20 glioma and risk was related to power level, we would predict = a=20 higher risk for analogue phone use than for digital phones. = As=20 in some6<= /A>=20 7<= /A>=20 1= 8=20 but not all8<= /A>=20 1= 0=20 previous reports we found no association between risk = of glioma=20 and use of analogue phones overall or with time since = first=20 use, lifetime years of use, or cumulative hours or = number of=20 calls.

In Sweden Hardell et al reported raised risks for mobile = phone=20 use ipsilateral to the side of development of high grade=20 astrocytomas (the principal subtype of glioma)8<= /A>=20 and for rural use in different analyses of the same=20 study.9<= /A>=20 Several other studies, however, could not confirm these = results=20 and the methods were criticised.3<= /A>=20 2= 0=20 2= 1=20 Our laterality analyses both showed a significantly raised = risk=20 for ipsilateral phone use. Using the methods of Lonn et=20 al,1= 7=20 however, we found a significantly reduced risk for = contralateral=20 use. These "complementary risks" above and below unity, = which=20 we observed for all measures of mobile phone use, can = probably=20 be explained by recall bias.2= 1=20 The patients with glioma, who were aware of the = location of=20 their tumour, may have considered that mobile phone use = was a=20 cause of its development, resulting in systematically=20 over-reporting of phone use on the side of the head = where their=20 cancer occurred. Generally, individuals are likely to=20 overestimate their actual use of mobile phones,2= 2=20 and this may have exaggerated the effect of differential=20 reporting for laterality. To investigate this issue = further, we=20 made case-control comparisons by handedness as people = tend to=20 use the phone on their handed side and because = handedness is a=20 variable reported at interview and not likely to be = subject to=20 recall bias. The clear pattern of significant odds = ratios above=20 and below unity for ipsilateral and contralateral = mobile phone=20 use, respectively, was not seen for handedness in = equivalent=20 analyses.

Potential bias
Case-control studies are = subject to=20 certain biases and particularly participation = bias.2= 3=20 We interviewed 51% of those patients with glioma who = were=20 eligible, mainly because rapid death prevented us from=20 approaching all of them. As early death is most likely = in=20 patients with high grade tumours, it is not surprising that=20 participation rates were higher in those with low grade=20 tumours. A bias in these results would occur only if = mobile=20 phone use was related to severity of tumour, which was = not=20 supported by our analysis, where odds ratios for mobile = phone=20 use showed no increased risk for high or low grade=20 tumours.

There is also potential for the introduction of = participation=20 bias into the control group. All controls were selected to=20 represent the general population by using the sampling = frame of=20 general practitioners' lists. Although methods varied = between=20 the south east and northern centres, the analysis = strategy of=20 frequency matching permitted a combined approach. The = overall=20 response rate for controls was relatively low (45%) = compared=20 with previously published studies from the Nordic=20 countries6<= /A>=20 7<= /A>=20 on mobile phone use and risk of glioma. Recruitment of = controls=20 was a complicated procedure, and we tried to optimise=20 participation rates. Prevailing legislation on consent = from=20 patients made the process a resource intensive exercise = for=20 general practitioners and in some instances the study = could not=20 follow-up patients directly, instead relying on general = practitioners to undertake this process. The principal = reason=20 for non-participation of controls was that they were=20 "uncontactable," and constraints imposed by ethical = approval=20 bodies prevented more than one follow-up attempt. It is = likely,=20 therefore, that some of the apparent non-responders were = in=20 fact individuals who were never contacted and therefore = had=20 no opportunity to respond. Our interviewed controls were = more=20 affluent than their non-interviewed counterparts and the=20 interviewed patients with glioma. Though we adjusted = for=20 deprivation in all the analyses, this cannot completely = remove=20 its potential influence.

There is generally a lack of convincing and consistent = evidence=20 of any effect of exposure to radiofrequency field on risk = of=20 cancer.2= 4=20 2= 5=20 Overall our findings are consistent with this and with = most=20 studies on mobile phone use. The positive association = found=20 between risk of glioma and ipsilateral mobile phone use = was=20 accompanied by a negative association for the opposite side = of=20 use to the tumour. Although it is possible the ipsilateral=20 association represents a real effect, this finding is = probably=20 explained by recall bias, with patients with glioma=20 systematically over-reporting use on the same side as = their=20 tumour and consequently under-reporting use on the = opposite=20 side. This study suggests that there are no = substantially=20 raised risks of glioma in the 10 years after first = mobile phone=20 use. Only future studies will be able to address longer = latency=20 periods for the development of glioma.


What = is already=20 known on this topic

Gliomas are a specific type of brain = tumour for=20 which the causes are generally unknown, but = concern=20 has been expressed over a possible link with = using=20 a mobile phone

What this study adds

This large case-control study found no = increased=20 risk of developing a glioma associated with = mobile=20 phone use either in the short or medium term =

We thank all the individuals who = were=20 interviewed for this project; all the study = interviewers,=20 administrators, and computer programmers who collected = and=20 processed the data; and Elisabeth Cardis, the = coordinator of=20 the Interphone study, and her colleagues for support = and=20 provision of data. The Northern UK study acknowledges = the=20 support of the membership of the study steering group chaired = by David Coggon and the following neuropathologists,=20 neuroradiologists, neurosurgeons, neuro-oncologists, = clinical=20 oncologists, neurologists, specialist nurses, and=20 administrators based in hospitals located in Scotland = (P=20 Barlow, I Bone, J Brown, J Crowther, RDolan, L Dunn, M = O=20 Fitzpatrick, M Fraser, R Grant, A Gregor, J Ironside, R = Johnstone, K W Lyndsay, S Macnamara, J Mair, R Mills, L = Myles,=20 B O'Reilly, V Papanastassiou, R Rampling, M Russell, D = Sim,=20 P Statham, J Steers, W A Taylor, G Teasdale, I Whittle), = West=20 Midlands (J M Anderson, P Barber, C R Barraclough, P = Bennett,=20 H G Boddie, A Brind, P Carey, M Choksey, M Christie, R N=20 Corston, G S Cruickshank, A Detta, P Dias, S J Ellis, G = Flint,=20 D A Francis, A H Grubneac, S P Harland, C Hawkins, T = Heafield,=20 R C Hughes, D G Jamieson, A Logan, CHAMeyer,RMitchell, = K=20 Morrison, P Newman, D Nicholl, S Nightingale, H S Pall, = J R=20 Ponsford, A Shehu, J Singh, J A Spillane, P Stanworth, = B=20 Summers, A R Walsh, J Wasserberg, A C Williams, J = Winer, S=20 Zygmunt), Trent (R J Abbott, S Adams, R D Ashpole, R D = E=20 Battersby, L Blumhardt, P Byrne, M Cartmill, S C Coley, = P=20 Critchley, B B Faraj, A Gibson, P Griffiths, R = Grunwald, T J=20 Hodgson, D T Hope, S Howell, D Jefferson, D Jelinek, N = Jordan,=20 A Kemeny, M C Lawden, J Lowe, N Messios, Kirsty Pardoe, = S=20 Price, I F Pye, M Radatz, I Robertson, K Robson, C = Romanowski,=20 G Sawle, B Sharrock, P Shaw, C Smith, W Temperley, G = Venables,=20 B White, A M Whiteley, AJ Wills), and West Yorkshire (A S = N=20 Al-Din, D Ash, J Bamford, M Bond, G Bonsor, L Bridges, B = Carey,=20 A Chakrabarty, P Chumas, D Dafalla, H Ford, G E Gerrard, P = J=20 Goulding, J Howe, S Jamieson, M H Johnson, L A Louizou, P=20 Marks, M Nelson, S Omer, N Phillips, S Ross, I = Rothwell, H=20 Spokes, J Straiton, G Towns, A Tyagi, P Vanhille, M = Busby).The=20 Southeast England study thanks D Hogben for study=20 administration and their research nurses, A Butlin, J = Owens, A=20 Hart, R Knight, C Parsley, M Pelerin, K Sampson and M = Swanwick,=20 for data collection. They thank H M=F8ller, B Plewa, = and S=20 Richards from the Thames Cancer Registry and the = following=20 neuropathologists, neurosurgeons, neuro-oncologists, = clinical=20 oncologists, neurologists, administrators, and = secretaries for=20 the help they provided: D G Hardy, P J Kilpatrick, R = Macfarlane=20 (Addenbrooke's Hospital); M Cronin, T Foster, S Furey, = M G=20 Glaser, F Jones, N D Mendoza, E S Newlands, K S O'Neill, = D=20 Peterson, F Taylor, J van Dellon (Charing Cross Hospital); = J J=20 Bending (Eastbourne District Hospital); P R Bullock, C = Chandler,=20 B Chitnavis, L Doey, R W Gullan, C E Polkey, R Selway, M M=20 Sharr, L Smith, A J Strong, N Thomas (King's College = Hospital);=20 G M Sadler (Maidstone Hospital); S Short (Mount Vernon=20 Hospital); S Brandner, A D Cheesman, J P Grieve, W J = Harkness,=20 R Kapoor, N D Kitchen, T Pearce, M P Powell, J Rees, F=20 Scaravilli, D T Thomas, L D Watkins (National Hospital = for=20 Neurology and Neurosurgery); A R Aspoas, S Bavetta, J C = Benjamin, K M David, J R Pollock, E Sims (Oldchurch = Hospital);=20 J Armstrong, J Akinwunmi, G Critchley, L Gunasekera, C=20 Hardwidge, J S Norris, P E Rose, P H Walter, P J Ward, = M=20 Wilkins (Princess Royal Hospital); T Z Aziz, D Kerr, P = J Teddy=20 (Radcliffe Infirmary); M Allen, T Dale, R Bradford, A P = Dhillon, N L Dorward, D Farraday-Browne, D J McLaughlin, = R S=20 Maurice-Williams, K Pigott, B Reynolds, C Shah, C Shieff, = E M=20 Wilson (Royal Free Hospital); F Afshar, H E Ellamushi, P = M=20 Richardson, H I Sabin, J Wadley (Royal London Hospital); M=20 Brada, F H Saran, D Traish (Royal Marsden Hospital); S = Whitaker=20 (Royal Surrey County Hospital); P N Plowman (St = Bartholomew's=20 Hospital); Carole Bramwell, A Bell, F Johnston, H Marsh, A=20 Martin, P S Minhas, A Moore, S Stapleton, S Wilson (St = George's=20 Hospital); R P Beaney (St Thomas' Hospital). =

Contributors: PAMcK, MJS, KRM, = MJAvT, and=20 AJS were responsible for the design and implementation = of the=20 study. SJH and MJS conducted the statistical analysis. = PAMcK=20 and SJH wrote the first draft of the paper. All = coauthors=20 provided comments on the draft. PAMcK is the guarantor. = Funding: The south east and northern UK studies = received=20 funding from the Mobile Telecommunications, Health and = Research=20 (MTHR) programme and as part of the Interphone study = from the=20 EU, the Mobile Manufacturers Forum, and the GSM = Association=20 through the scientifically independent Union Internationale=20 Contre le Cancer (UICC). In addition the northern UK study=20 received funding from the Health and Safety Executive, = the=20 Department of Health, the UK network operators = (O2,=20 Orange, T-Mobile, Vodafone, 3), and the Scottish=20 Executive.

Competing interest: The = University of Leeds=20 has received some financial support on behalf of the = four=20 centres of the UK northern study from the UK network = operators=20 (O2, Orange, T-Mobile, Vodafone, 3) under = legal=20 signed contractual agreements which ensure complete=20 independence for the scientific investigators. While = employed=20 at the University of Birmingham MJAvT received funding = from=20 O2, Orange, T-Mobile, and Vodafone to carry out a = feasibility study of health effects from radiofrequency = exposure among employees of broadcasting and = telecommunication=20 industries.

Ethical approval: Multicentre = research=20 ethics committees for the south east and Scotland and = all=20 relevant local research ethics committees.

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(Accepted 14 November 2005)


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Mobile phone use and risk of glioma in adults: = case-control=20 study.=20
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bmj.com, 3 Feb 2006 [Ful= l=20 text]=20
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Opera = requires=0A= the Sun Java Runtime Environment .=0A= =0A= by Andrew Gregory=0A= http://www.scss.com.au/family/andrew/webdesign/xmlhttprequest/=0A= =0A= This work is licensed under the Creative Commons Attribution License. To = view a=0A= copy of this license, visit = http://creativecommons.org/licenses/by-sa/2.5/ or=0A= send a letter to Creative Commons, 559 Nathan Abbott Way, Stanford, = California=0A= 94305, USA.=0A= =0A= Attribution: Leave my name and web address in this script intact.=0A= =0A= Not Supported in Opera=0A= ----------------------=0A= * user/password authentication=0A= * responseXML data member=0A= =0A= Not Fully Supported in Opera=0A= ----------------------------=0A= * async requests=0A= * abort()=0A= * getAllResponseHeaders(), getAllResponseHeader(header)=0A= =0A= */=0A= // IE support=0A= if (window.ActiveXObject && !window.XMLHttpRequest) {=0A= window.XMLHttpRequest =3D function() {=0A= var msxmls =3D new Array(=0A= 'Msxml2.XMLHTTP.5.0',=0A= 'Msxml2.XMLHTTP.4.0',=0A= 'Msxml2.XMLHTTP.3.0',=0A= 'Msxml2.XMLHTTP',=0A= 'Microsoft.XMLHTTP');=0A= for (var i =3D 0; i < msxmls.length; i++) {=0A= try {=0A= return new ActiveXObject(msxmls[i]);=0A= } catch (e) {=0A= }=0A= }=0A= return null;=0A= };=0A= }=0A= // Gecko support=0A= /* ;-) */=0A= // Opera support=0A= if (window.opera && !window.XMLHttpRequest) {=0A= window.XMLHttpRequest =3D function() {=0A= this.readyState =3D 0; // = 0=3Duninitialized,1=3Dloading,2=3Dloaded,3=3Dinteractive,4=3Dcomplete=0A= this.status =3D 0; // HTTP status codes=0A= this.statusText =3D '';=0A= this._headers =3D [];=0A= this._aborted =3D false;=0A= this._async =3D true;=0A= this._defaultCharset =3D 'ISO-8859-1';=0A= this._getCharset =3D function() {=0A= var charset =3D _defaultCharset;=0A= var contentType =3D = this.getResponseHeader('Content-type').toUpperCase();=0A= val =3D contentType.indexOf('CHARSET=3D');=0A= if (val !=3D -1) {=0A= charset =3D contentType.substring(val);=0A= }=0A= val =3D charset.indexOf(';');=0A= if (val !=3D -1) {=0A= charset =3D charset.substring(0, val);=0A= }=0A= val =3D charset.indexOf(',');=0A= if (val !=3D -1) {=0A= charset =3D charset.substring(0, val);=0A= }=0A= return charset;=0A= };=0A= this.abort =3D function() {=0A= this._aborted =3D true;=0A= };=0A= this.getAllResponseHeaders =3D function() {=0A= return this.getAllResponseHeader('*');=0A= };=0A= this.getAllResponseHeader =3D function(header) {=0A= var ret =3D '';=0A= for (var i =3D 0; i < this._headers.length; i++) {=0A= if (header =3D=3D '*' || this._headers[i].h =3D=3D header) {=0A= ret +=3D this._headers[i].h + ': ' + this._headers[i].v + '\n';=0A= }=0A= }=0A= return ret;=0A= };=0A= this.getResponseHeader =3D function(header) {=0A= var ret =3D getAllResponseHeader(header);=0A= var i =3D ret.indexOf('\n');=0A= if (i !=3D -1) {=0A= ret =3D ret.substring(0, i);=0A= }=0A= return ret;=0A= };=0A= this.setRequestHeader =3D function(header, value) {=0A= this._headers[this._headers.length] =3D {h:header, v:value};=0A= };=0A= this.open =3D function(method, url, async, user, password) {=0A= this.method =3D method;=0A= this.url =3D url;=0A= this._async =3D true;=0A= this._aborted =3D false;=0A= this._headers =3D [];=0A= if (arguments.length >=3D 3) {=0A= this._async =3D async;=0A= }=0A= if (arguments.length > 3) {=0A= opera.postError('XMLHttpRequest.open() - user/password not = supported');=0A= }=0A= this.readyState =3D 1;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= };=0A= this.send =3D function(data) {=0A= if (!navigator.javaEnabled()) {=0A= alert("XMLHttpRequest.send() - Java must be installed and = enabled.");=0A= return;=0A= }=0A= if (this._async) {=0A= setTimeout(this._sendasync, 0, this, data);=0A= // this is not really asynchronous and won't execute until the = current=0A= // execution context ends=0A= } else {=0A= this._sendsync(data);=0A= }=0A= }=0A= this._sendasync =3D function(req, data) {=0A= if (!req._aborted) {=0A= req._sendsync(data);=0A= }=0A= };=0A= this._sendsync =3D function(data) {=0A= this.readyState =3D 2;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= // open connection=0A= var url =3D new java.net.URL(new = java.net.URL(window.location.href), this.url);=0A= var conn =3D url.openConnection();=0A= for (var i =3D 0; i < this._headers.length; i++) {=0A= conn.setRequestProperty(this._headers[i].h, this._headers[i].v);=0A= }=0A= this._headers =3D [];=0A= if (this.method =3D=3D 'POST') {=0A= // POST data=0A= conn.setDoOutput(true);=0A= var wr =3D new = java.io.OutputStreamWriter(conn.getOutputStream(), this._getCharset());=0A= wr.write(data);=0A= wr.flush();=0A= wr.close();=0A= }=0A= // read response headers=0A= // NOTE: the getHeaderField() methods always return nulls for me :(=0A= var gotContentEncoding =3D false;=0A= var gotContentLength =3D false;=0A= var gotContentType =3D false;=0A= var gotDate =3D false;=0A= var gotExpiration =3D false;=0A= var gotLastModified =3D false;=0A= for (var i =3D 0; ; i++) {=0A= var hdrName =3D conn.getHeaderFieldKey(i);=0A= var hdrValue =3D conn.getHeaderField(i);=0A= if (hdrName =3D=3D null && hdrValue =3D=3D null) {=0A= break;=0A= }=0A= if (hdrName !=3D null) {=0A= this._headers[this._headers.length] =3D {h:hdrName, = v:hdrValue};=0A= switch (hdrName.toLowerCase()) {=0A= case 'content-encoding': gotContentEncoding =3D true; break;=0A= case 'content-length' : gotContentLength =3D true; break;=0A= case 'content-type' : gotContentType =3D true; break;=0A= case 'date' : gotDate =3D true; break;=0A= case 'expires' : gotExpiration =3D true; break;=0A= case 'last-modified' : gotLastModified =3D true; break;=0A= }=0A= }=0A= }=0A= // try to fill in any missing header information=0A= var val;=0A= val =3D conn.getContentEncoding();=0A= if (val !=3D null && !gotContentEncoding) = this._headers[this._headers.length] =3D {h:'Content-encoding', v:val};=0A= val =3D conn.getContentLength();=0A= if (val !=3D -1 && !gotContentLength) = this._headers[this._headers.length] =3D {h:'Content-length', v:val};=0A= val =3D conn.getContentType();=0A= if (val !=3D null && !gotContentType) = this._headers[this._headers.length] =3D {h:'Content-type', v:val};=0A= val =3D conn.getDate();=0A= if (val !=3D 0 && !gotDate) this._headers[this._headers.length] = =3D {h:'Date', v:(new Date(val)).toUTCString()};=0A= val =3D conn.getExpiration();=0A= if (val !=3D 0 && !gotExpiration) = this._headers[this._headers.length] =3D {h:'Expires', v:(new = Date(val)).toUTCString()};=0A= val =3D conn.getLastModified();=0A= if (val !=3D 0 && !gotLastModified) = this._headers[this._headers.length] =3D {h:'Last-modified', v:(new = Date(val)).toUTCString()};=0A= // read response data=0A= var reqdata =3D '';=0A= var stream =3D conn.getInputStream();=0A= if (stream) {=0A= var reader =3D new java.io.BufferedReader(new = java.io.InputStreamReader(stream, this._getCharset()));=0A= var line;=0A= while ((line =3D reader.readLine()) !=3D null) {=0A= if (this.readyState =3D=3D 2) {=0A= this.readyState =3D 3;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= }=0A= reqdata +=3D line + '\n';=0A= }=0A= reader.close();=0A= this.status =3D 200;=0A= this.statusText =3D 'OK';=0A= this.responseText =3D reqdata;=0A= this.readyState =3D 4;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= if (this.onload) {=0A= this.onload();=0A= }=0A= } else {=0A= // error=0A= this.status =3D 404;=0A= this.statusText =3D 'Not Found';=0A= this.responseText =3D '';=0A= this.readyState =3D 4;=0A= if (this.onreadystatechange) {=0A= this.onreadystatechange();=0A= }=0A= if (this.onerror) {=0A= this.onerror();=0A= }=0A= }=0A= };=0A= };=0A= }=0A= // ActiveXObject emulation=0A= if (!window.ActiveXObject && window.XMLHttpRequest) {=0A= window.ActiveXObject =3D function(type) {=0A= switch (type.toLowerCase()) {=0A= case 'microsoft.xmlhttp':=0A= case 'msxml2.xmlhttp':=0A= case 'msxml2.xmlhttp.3.0':=0A= case 'msxml2.xmlhttp.4.0':=0A= case 'msxml2.xmlhttp.5.0':=0A= return new XMLHttpRequest();=0A= }=0A= return null;=0A= };=0A= }=0A= ------=_NextPart_000_0021_01C678C2.CC08B8B0 Content-Type: application/octet-stream Content-Transfer-Encoding: quoted-printable Content-Location: http://bmj.bmjjournals.com/javascript/ajax/utility.js /************************************************************************= *****=0A= * javascript/ajax/utility.js=0A= *=0A= * Utility functions for working with XMLHttpRequest data.=0A= *=0A= * Copyright 2006 Board of Trustees of the Leland Stanford Junior = University.=0A= = *************************************************************************= ***/=0A= =0A= /*=0A= * Copy XML nodes into an HTMLElement. This effectively=0A= * clones XML markup which uses XHTML naming conventions=0A= * into an HTML DOM.=0A= */=0A= function copy_xml_to_html(src, dst) {=0A= if (src.nodeType =3D=3D 1) { /* Node.ELEMENT_NODE */=0A= var e =3D document.createElement(src.nodeName);=0A= for (var i =3D 0; i < src.childNodes.length; i++) {=0A= copy_xml_to_html(src.childNodes[i], e);=0A= }=0A= for (var i =3D 0; i < src.attributes.length; i++) {=0A= var n =3D src.attributes[i].name;=0A= var v =3D unescape_xml_string(src.attributes[i].value); =0A= e.setAttribute(n, v);=0A= if (n =3D=3D "class") {=0A= e.className =3D v;=0A= }=0A= else if (n =3D=3D "style") {=0A= set_css_style(v, e, "");=0A= }=0A= }=0A= dst.appendChild(e);=0A= }=0A= else if (src.nodeType =3D=3D 3) { /* Node.TEXT_NODE */=0A= dst.appendChild(document.createTextNode(src.nodeValue));=0A= }=0A= }=0A= =0A= /* =0A= * It is unclear that this is the right thing to be calling=0A= * from copy_xml_to_html, but it appears that Safari decides=0A= * to convert & to the NCR #, and then encodes that=0A= * NCR to &%26%2338;. So, I'm going to treat the DOM Attr=0A= * value as a plain string, and run our XML string input=0A= * through the decoding routine below.=0A= */=0A= function unescape_xml_string(s) {=0A= return s.replace(/'/g, "'")=0A= .replace(/'/g, "'")=0A= .replace(/"/g, "\"")=0A= .replace(/"/g, "\"")=0A= .replace(/>/g, ">")=0A= .replace(/>/g, ">")=0A= .replace(/</g, "<")=0A= .replace(/</g, "<")=0A= .replace(/&/g, "&")=0A= .replace(/&/g, "&");=0A= }=0A= =0A= /*=0A= * Parse set of CSS rules and apply them to an element.=0A= * This is quite horrifying, but I'm unable to determine=0A= * how else to handle this with IE 6. FireFox and other=0A= * sane browsers let you simply set the style attribute=0A= * or use e.style.setProperty(rule, value, priority),=0A= * IE 6 appears to have neither of these capabilities..=0A= */=0A= function set_css_style(css, e, priority) {=0A= var rules =3D css.split(";");=0A= for (var i =3D 0; i < rules.length; i++) {=0A= var nvpair =3D rules[i].split(":");=0A= if (nvpair.length =3D=3D 2) {=0A= try {=0A= var name =3D nvpair[0]; /* style attribute */=0A= var value =3D nvpair[1]; /* attribute value */=0A= =0A= /*=0A= * For each possible style attribute, set the=0A= * appropriate style property in the element.=0A= */=0A= if (name =3D=3D "background") {=0A= e.style.background =3D value;=0A= }=0A= else if (name =3D=3D "background-attachment") {=0A= e.style.backgroundAttachment =3D value;=0A= }=0A= else if (name =3D=3D "background-color") {=0A= e.style.backgroundColor =3D value;=0A= }=0A= else if (name =3D=3D "background-image") {=0A= e.style.backgroundImage =3D value;=0A= }=0A= else if (name =3D=3D "background-position") {=0A= e.style.backgroundPosition =3D value;=0A= }=0A= else if (name =3D=3D "background-position-x") {=0A= e.style.backgroundPositionX =3D value;=0A= }=0A= else if (name =3D=3D "background-position-y") {=0A= e.style.backgroundPositionY =3D value;=0A= }=0A= else if (name =3D=3D "background-repeat") {=0A= e.style.backgroundRepeat =3D value;=0A= }=0A= else if (name =3D=3D "behavior") {=0A= e.style.behavior =3D value;=0A= }=0A= else if (name =3D=3D "border") {=0A= e.style.border =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom") {=0A= e.style.borderBottom =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-color") {=0A= e.style.borderBottomColor =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-style") {=0A= e.style.borderBottomStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-bottom-width") {=0A= e.style.borderBottomWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-collapse") {=0A= e.style.borderCollapse =3D value;=0A= }=0A= else if (name =3D=3D "border-color") {=0A= e.style.borderColor =3D value;=0A= }=0A= else if (name =3D=3D "border-left") {=0A= e.style.borderLeft =3D value;=0A= }=0A= else if (name =3D=3D "border-left-color") {=0A= e.style.borderLeftColor =3D value;=0A= }=0A= else if (name =3D=3D "border-left-style") {=0A= e.style.borderLeftStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-left-width") {=0A= e.style.borderLeftWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-right") {=0A= e.style.borderRight =3D value;=0A= }=0A= else if (name =3D=3D "border-right-color") {=0A= e.style.borderRightColor =3D value;=0A= }=0A= else if (name =3D=3D "border-right-style") {=0A= e.style.borderRightStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-right-width") {=0A= e.style.borderRightWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-style") {=0A= e.style.borderStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-top") {=0A= e.style.borderTop =3D value;=0A= }=0A= else if (name =3D=3D "border-top-color") {=0A= e.style.borderTopColor =3D value;=0A= }=0A= else if (name =3D=3D "border-top-style") {=0A= e.style.borderTopStyle =3D value;=0A= }=0A= else if (name =3D=3D "border-top-width") {=0A= e.style.borderTopWidth =3D value;=0A= }=0A= else if (name =3D=3D "border-width") {=0A= e.style.borderWidth =3D value;=0A= }=0A= else if (name =3D=3D "bottom") {=0A= e.style.bottom =3D value;=0A= }=0A= else if (name =3D=3D "clear") {=0A= e.style.clear =3D value;=0A= }=0A= else if (name =3D=3D "clip") {=0A= e.style.clip =3D value;=0A= }=0A= else if (name =3D=3D "color") {=0A= e.style.color =3D value;=0A= }=0A= else if (name =3D=3D "cssText") {=0A= e.style.Sets =3D value;=0A= }=0A= else if (name =3D=3D "cursor") {=0A= e.style.cursor =3D value;=0A= }=0A= else if (name =3D=3D "direction") {=0A= e.style.direction =3D value;=0A= }=0A= else if (name =3D=3D "display") {=0A= e.style.display =3D value;=0A= }=0A= else if (name =3D=3D "font") {=0A= e.style.font =3D value;=0A= }=0A= else if (name =3D=3D "font-family") {=0A= e.style.fontFamily =3D value;=0A= }=0A= else if (name =3D=3D "font-size") {=0A= e.style.fontSize =3D value;=0A= }=0A= else if (name =3D=3D "font-style") {=0A= e.style.fontStyle =3D value;=0A= }=0A= else if (name =3D=3D "font-variant") {=0A= e.style.fontVariant =3D value;=0A= }=0A= else if (name =3D=3D "font-weight") {=0A= e.style.fontWeight =3D value;=0A= }=0A= else if (name =3D=3D "height") {=0A= e.style.height =3D value;=0A= }=0A= else if (name =3D=3D "ime-mode") {=0A= e.style.imeMode =3D value;=0A= }=0A= else if (name =3D=3D "layout-flow") {=0A= e.style.layoutFlow =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid") {=0A= e.style.layoutGrid =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-char") {=0A= e.style.layoutGridChar =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-line") {=0A= e.style.layoutGridLine =3D value;=0A= }=0A= else if (name =3D=3D "layout-grid-mode") {=0A= e.style.layoutGridMode =3D value;=0A= }=0A= else if (name 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