Elsevier

The Lancet

Volume 353, Issue 9154, 27 February 1999, Pages 693-697
The Lancet

Articles
Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study

https://doi.org/10.1016/S0140-6736(98)08138-0Get rights and content

Summary

Background

Apart from the small number of iatrogenic and familial cases, the cause of most cases of Creutzfeldt-Jakob disease (CJD) is not known. We aimed to identify risk factors for sporadic CJD.

Methods

In a case-control study, we compared the medical history and selected demographic characteristics of 241 definite (neuropathologically confirmed) and probable (clinically likely) patients with CJD, ascertained from the Australian National Creutzfeldt-Jakob Disease Registry between Jan 1, 1970, and October 31, 1997, and of 784 controls, recruited from the community by random telephone interview in August, 1997. Standard logistic regression was used for the comparisons.

Findings

Surgical procedures were significantly associated with the development of sporadic CJD. This risk progressively increased with the number of surgical treatments to a maximum for three procedures (odds ratio 2·13 [95% CI 1·34–3·41], p=0·002). There was also a significant association between risk of CJD and residence or employment on a farm (p<0·001) or market garden (p=0·002) for longer than 10 years. We found no significant risk associated with a history of blood transfusion, organ transplantation, major dental work, or occupation.

Interpretation

Our findings accord with the hypothesis that a range of surgical treatments may serve as unrecognised contamination events and account for a proportion of cases of sporadic CJD. Possible biases in different methods and times for the acquisition of data on cases and controls suggest our findings need to be replicated in independent studies with community controls.

Introduction

By contrast with iatrogenic and familial cases of Creutzfeldt-Jakob disease (CJD), the aetiology of the most common form, sporadic CJD, which constitutes 85–90% of all cases,1, 2 is unknown. One hypothesis is that sporadic disease is caused by a rare (one in a million) spontaneous somatic mutation within the cerebral neuronal pool of the prion protein (PrP).3 An alternative is low-level contamination events.4 The excess of homozygosity at codon 129 in iatrogenic disease5 has also been found in sporadic CJD, and may increase the chance of normal PrP (PrPC) converting to the abnormal, disease-associated isoform (PrPSC) when the normal and abnormal conformers interact, as could occur after a contamination event.

Previous case-control studies have investigated possible causes or risk factors for sporadic CJD, without identifying any consistent or major influences.7, 8, 9, 10, 11, 12, 13, 14 In our case-control study of risk factors for sporadic CJD, we used the Australian National Creutzfeldt-Jakob Disease Registry to ascertain cases. Controls were recruited from the general community by random telephone survey, unlike most previous studies that used hospital-based controls.9, 10, 11, 12, 13, 14

Section snippets

Cases

The Australian National Creutzfeldt-Jakob Disease Registry 15 collected cases retrospectively to Jan 1, 1970, and prospectively from Oct 1, 1993. 241 patients with sporadic CJD (122 men, mean age 63·1 years, 119 women, mean age 66·6 years; combined age range 25–84 years) represented all Australian cases of sporadic CJD that occurred up to Oct 31, 1997. The diagnostic subclassifications of this cohort were 151 definite (neuropathologically confirmed) and 90 probable (clinically likely) cases of

Results

784 controls completed the telephone interview. 12 387 telephone calls were made, 2577 (21%) of which were number unobtainable, engaged, or no reply, and in 22 (0·2%) calls an appointment was made to ring back. In 1308 (11%) of the calls, permission for the interview was refused, and in 7349 (60%), the relevant age, sex, and urban or rural residence quota was full. Of the 1131 calls in which interviews began, 347 calls were halted—the respondent did not want to continue in 63 (6%), there were

Discussion

In this case-control study, we found a range of surgical treatments were associated with an increased risk of sporadic CJD. Two previous case-control studies, also with community controls, found the risk of CJD was associated with hospital-related therapy,8, 9 but this significance was lost when the data were pooled as part of a meta-analysis.13 The absence of this finding in a third study12 may reflect methodological differences, since the controls were selected only from hospital populations

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