MR795 - Cancer Risk & Mortality in a Sample of Service Personnel Deployed to Bosnia 1992 - 1996

The King's Centre for Military Health Research (KCMHR) requires access to NHS England data for the purpose of the following research project: 'Cancer Risk & Mortality in a Sample of Service Personnel Deployed to Bosnia 1992 - 1996'. KCMHR is a research centre within King's College London (KCL).

Background:

There has been much speculation that military personnel who served on UN peacekeeping duties in Bosnia in 1992-1996 have higher than expected rates of cancer. This speculation has been based on individual case reports and some small clusters of leukaemia reported in Italian armed forces. It has been suggested that the allegedly higher rates of cancer are due to exposure to depleted uranium during deployment (Mayor, 2001). Other European nations have carried out studies to ascertain the incidence of cancer in their Bosnia veterans (Bogers et al, 2013; Gustavsson et al, 2004; Peragallo et al, 2010; Storm et al, 2006). In order to ascertain the rates of cancer and deaths in UK veterans who served in Bosnia, it is necessary to carry out systematic epidemiological studies and to date these have not been done. The study will determine whether the rates of cancer and death among personnel who served in Bosnia are higher than expected.

In 1997/8, using information provided by the Ministry of Defence (MoD), KCL contacted members of UK Armed Forces who had deployed to Bosnia on UN peacekeeping duties as part of a larger study looking at the health consequences of the 1991 Gulf War. Data was collected using a questionnaire.

In 1997/8, KCMHR conducted a large epidemiological study on the health consequences of the 1990- 1991 Gulf War (Unwin et al, 1999). This involved identifying a cohort of 4250 individuals who had served in the Gulf, and two comparison groups: 4250 who had served on peace-keeping duties in Bosnia between 1992 and 1996, and 4250 individuals who were in the UK military at the time of the 1990-1991 Gulf War. In addition to demographic, health and service-related data, environmental and combat related exposure data were collected from study responders.

The Cohort

In 2006 name, address, date of birth, and NHS number of the sample of UK Armed Forces personnel, who had deployed to Bosnia between 1992 and 1996 were sent from the KCMHR to the ONS so that they could be identified and flagged for long-term follow-up. Self-reported data (and MoD provided data) relating to the Bosnia cohort have been retained as part of the KCL Gulf War study, with data relevant to addressing the aims of this additional sub-study held separately (the Bosnia study database).

Of the 4500 people sampled into the Bosnia group, 2620 responded to the questionnaire study. 2470 of those who responded were successfully flagged, and any death and cancer notifications or embarkations have been sent by ONS and subsequently by NHS Digital (after the service transferred in 2008) to KCMHR for this cohort.

Until 2014, the Bosnia study database held person identifying data along with cancer notifications and death registration details. On 27/03/2014, all directly identifying data had been removed from the Bosnia database, all hard copy notifications shredded and person identifying details deleted from notifications received electronically. The Bosnia study data are pseudonymised. However, the personal data that relate the original KCL Gulf War study are still held at KCL (and will continue to be in anticipation of a possible follow up study). However, these data cannot be accessed by researchers from the Bosnia study.

In 2004 ethics committee approval was granted to ‘flag’ the Bosnia cohort and to obtain cancer registration and death notifications (Joint South London and Maudsley (SLAM)/Institute of Psychology (IOP) NHS Research Ethics Committee (REC), study number 055/04). Section 60 of the Health & Social Care Act 2001 support was applied for and was granted in 2006 to supply patient identifiable data to NHS Digital, to flag the cohort and, for study responders, to supply death registration data, cancer registration data and exit information. For study non-responders summary tables for mortality and cancer incidence would be supplied at the end of the study. NHS England was provided with details of the Bosnia cohort (i.e. name, address, date of birth, and NHS number where available). A database of the study responders who were successfully flagged was compiled and is updated with details of cancer registrations and deaths as and when notifications are received from NHS England. In 2014 KCMHR again sought and received a favourable ethical review to continue to receive data from NHS England (REC reference 14/LO/1141, IRAS project ID 151260).

Study aims

The immediate aim is to ascertain if the number of cancers and deaths reported so far would give sufficient power for meaningful analysis. Once researchers have the latest numbers of cancers and the number of deaths, a power calculation can be carried out to see if there is sufficient power (at least 80%) to show a clinically significant difference between the Bosnia group and a control group. Calculation showed that there were sufficient numbers to show a relative risk of 1.7 in the Bosnia cohort compared to the era group, in other words if there was an increased risk of cancer in the Bosnia cohort of 70% there would be sufficient power to detect it. That was based on the absolute risk of cancer reported by MacFarlane et al who found a low risk (0.5%) of cancer in the era group after 10 years. As time goes on, the absolute risk of cancer in both the era and Bosnia groups will increase (rates of cancers increase with age) so that after ~20 years it would be possible to detect a smaller increase in relative risk. There is not a specific number of cancers that would need to be reached in the Bosnia group since there may not actually be a difference in risk between the two groups. Of more importance is the length of time that needs to have elapsed since exposure for a possible difference in rate of cancer to have occurred. The latency period is the amount of time that elapses between initial exposure and the diagnosis of cancer. The latency period for blood related cancers e.g. non-Hodgkin lymphoma or myeloma have a shorter latency than solid tumours such as lung cancer. For example, the approximate latency period of lung cancer is approximately 14 years of stomach cancer is 22 years and of kidney cancer is more than 40 years. It is now between 23 and 27 years since the Bosnia cohort deployed and this would be an appropriate time to assess whether the numbers of cancer notifications and /or deaths in this cohort compared to the era cohort show that there is an increased risk attributable to deployment to Bosnia.

If there have been sufficient occurrences KCMHR will not require further updates for the cohort.

For the longer term and main study aim KCMHR will ask the MoD to supply an anonymised dataset from the flagged “era group” containing information on age, sex, rank and cancer registrations and deaths. Researchers will then be able to compare cancer registrations and deaths in the Bosnia group with a non-deployed group serving at the same time, controlling for age, sex and rank. By comparing to data from the original study (Unwin et al, 1999), researchers will be able to assess whether risk of cancer in the Bosnia cohort is related to reported exposures to potentially harmful materials during deployment.

The overall aim of the study is to compare the incidence of cancer in a cohort of UK armed forces personnel who deployed to Bosnia between 1992 and 1996 and a cohort of personnel who were in service at the time but did not deploy to Bosnia. Researchers will also compare the rate of cancer in the Bosnia group with that in the general UK population using publicly available national statistics of cancer and mortality. Additionally, it will be assessed whether the risk of cancer in the Bosnia group is associated with exposures to harmful materials during their deployment.

The specific research questions are:

1. Are individuals who served in Bosnia between 1992 and 1996 at greater risk of developing cancer than other military personnel who did not serve there?

2. Are individuals who served in Bosnia between 1992 and 1996 at greater risk of developing cancer than the general UK population?

3. Is risk of cancer in the Bosnia cohort related to self-reported exposures to potentially hazardous materials during deployment?

If it is found that military personnel who served on UN peacekeeping duties in Bosnia in 1992-1996 do not have higher than expected rates of cancer, the Ministry of Defence and the Service charities will have evidence to allay fears among this population that they are at increased risk.

If researchers find an association between serving in Bosnia and increased risk of certain cancers, heightened awareness among health service providers of this particular risk could lead to earlier diagnosis and improved quality of care. In addition, if researchers find an association between particular exposures and cancer, the Ministry Of Defence could act to protect personnel from such exposures in the future.

The pseudonymised data are required to be able to perform analyses described. The data is minimised to the cohort members within England & Wales, the research team have only requested fields required for the analysis.

King's College London are the sole data controllers for this research, decisions on how the data is processed are made by the substantive employees of King's College London. Data will only be accessed and processed by substantive employees of King's College London and will not be accessed or processed by any other third parties.

Funding

This study is supported by KCMHR internal funding.

Legal Basis

UK GDPR Article 6 (1) (e): This analysis is in the public interest since it seeks to provide important data which could inform treatment pathways for certain cancers and could inform decisions about particular patients within in the NHS.

UK GDPR Article 9 (2)(j): processing is necessary for scientific research purposes and shall be proportionate to the aim pursued, respect the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. This data request is necessary to allow the study team to conduct analysis which supports the research objectives.

The key milestone is the decision on if there is sufficient data to carry out significant analysis immediately or whether there is a need to wait a few years until further data is available.

This is a long-term study recording the cancer status of veterans of The UK Armed Forces deployments to Bosnia between 1992 and 1996. In view of the anticipated long latency period between exposure and the appearance of cancers there may not be sufficient data yet to carry out the analysis.

Once a decision has been made that there is sufficient data it is expected that the outputs will include:

- a report of the findings from the study with recommendations to the UK Ministry of Defence (MoD) and to Service charities dealing with veterans and their families (for example, The Royal British Legion, SSAFA). The report will include a lay summary which can be made available on the webpages of the MoD and Service charities.

- an academic paper giving an analysis and discussion of the results of the study that, subject to acceptance, will be published in an appropriate journal such as the British Medical Journal (BMJ).

- an infographic will be produced which will be hosted on the King’s website and distributed to all stakeholders for onward dissemination.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

There are not yet any yielded benefits, the study team are waiting for the data analysis from the study to be completed .

The King's Centre for Military Health Research (KCMHR) requires access to NHS England data for the purpose of the following research project: 'Cancer Risk & Mortality in a Sample of Service Personnel Deployed to Bosnia 1992 - 1996'. KCMHR is a research centre within King's College London (KCL).

Background:

There has been much speculation that military personnel who served on UN peacekeeping duties in Bosnia in 1992-1996 have higher than expected rates of cancer. This speculation has been based on individual case reports and some small clusters of leukaemia reported in Italian armed forces. It has been suggested that the allegedly higher rates of cancer are due to exposure to depleted uranium during deployment (Mayor, 2001). Other European nations have carried out studies to ascertain the incidence of cancer in their Bosnia veterans (Bogers et al, 2013; Gustavsson et al, 2004; Peragallo et al, 2010; Storm et al, 2006). In order to ascertain the rates of cancer and deaths in UK veterans who served in Bosnia, it is necessary to carry out systematic epidemiological studies and to date these have not been done. The study will determine whether the rates of cancer and death among personnel who served in Bosnia are higher than expected.

In 1997/8, using information provided by the Ministry of Defence (MoD), KCL contacted members of UK Armed Forces who had deployed to Bosnia on UN peacekeeping duties as part of a larger study looking at the health consequences of the 1991 Gulf War. Data was collected using a questionnaire.

In 1997/8, KCMHR conducted a large epidemiological study on the health consequences of the 1990- 1991 Gulf War (Unwin et al, 1999). This involved identifying a cohort of 4250 individuals who had served in the Gulf, and two comparison groups: 4250 who had served on peace-keeping duties in Bosnia between 1992 and 1996, and 4250 individuals who were in the UK military at the time of the 1990-1991 Gulf War. In addition to demographic, health and service-related data, environmental and combat related exposure data were collected from study responders.

The Cohort

In 2006 name, address, date of birth, and NHS number of the sample of UK Armed Forces personnel, who had deployed to Bosnia between 1992 and 1996 were sent from the KCMHR to the ONS so that they could be identified and flagged for long-term follow-up. Self-reported data (and MoD provided data) relating to the Bosnia cohort have been retained as part of the KCL Gulf War study, with data relevant to addressing the aims of this additional sub-study held separately (the Bosnia study database).

Of the 4500 people sampled into the Bosnia group, 2620 responded to the questionnaire study. 2470 of those who responded were successfully flagged, and any death and cancer notifications or embarkations have been sent by ONS and subsequently by NHS Digital (after the service transferred in 2008) to KCMHR for this cohort.

Until 2014, the Bosnia study database held person identifying data along with cancer notifications and death registration details. On 27/03/2014, all directly identifying data had been removed from the Bosnia database, all hard copy notifications shredded and person identifying details deleted from notifications received electronically. The Bosnia study data are pseudonymised. However, the personal data that relate the original KCL Gulf War study are still held at KCL (and will continue to be in anticipation of a possible follow up study). However, these data cannot be accessed by researchers from the Bosnia study.

In 2004 ethics committee approval was granted to ‘flag’ the Bosnia cohort and to obtain cancer registration and death notifications (Joint South London and Maudsley (SLAM)/Institute of Psychology (IOP) NHS Research Ethics Committee (REC), study number 055/04). Section 60 of the Health & Social Care Act 2001 support was applied for and was granted in 2006 to supply patient identifiable data to NHS Digital, to flag the cohort and, for study responders, to supply death registration data, cancer registration data and exit information. For study non-responders summary tables for mortality and cancer incidence would be supplied at the end of the study. NHS England was provided with details of the Bosnia cohort (i.e. name, address, date of birth, and NHS number where available). A database of the study responders who were successfully flagged was compiled and is updated with details of cancer registrations and deaths as and when notifications are received from NHS England. In 2014 KCMHR again sought and received a favourable ethical review to continue to receive data from NHS England (REC reference 14/LO/1141, IRAS project ID 151260).

Study aims

The immediate aim is to ascertain if the number of cancers and deaths reported so far would give sufficient power for meaningful analysis. Once researchers have the latest numbers of cancers and the number of deaths, a power calculation can be carried out to see if there is sufficient power (at least 80%) to show a clinically significant difference between the Bosnia group and a control group. Calculation showed that there were sufficient numbers to show a relative risk of 1.7 in the Bosnia cohort compared to the era group, in other words if there was an increased risk of cancer in the Bosnia cohort of 70% there would be sufficient power to detect it. That was based on the absolute risk of cancer reported by MacFarlane et al who found a low risk (0.5%) of cancer in the era group after 10 years. As time goes on, the absolute risk of cancer in both the era and Bosnia groups will increase (rates of cancers increase with age) so that after ~20 years it would be possible to detect a smaller increase in relative risk. There is not a specific number of cancers that would need to be reached in the Bosnia group since there may not actually be a difference in risk between the two groups. Of more importance is the length of time that needs to have elapsed since exposure for a possible difference in rate of cancer to have occurred. The latency period is the amount of time that elapses between initial exposure and the diagnosis of cancer. The latency period for blood related cancers e.g. non-Hodgkin lymphoma or myeloma have a shorter latency than solid tumours such as lung cancer. For example, the approximate latency period of lung cancer is approximately 14 years of stomach cancer is 22 years and of kidney cancer is more than 40 years. It is now between 23 and 27 years since the Bosnia cohort deployed and this would be an appropriate time to assess whether the numbers of cancer notifications and /or deaths in this cohort compared to the era cohort show that there is an increased risk attributable to deployment to Bosnia.

If there have been sufficient occurrences KCMHR will not require further updates for the cohort.

For the longer term and main study aim KCMHR will ask the MoD to supply an anonymised dataset from the flagged “era group” containing information on age, sex, rank and cancer registrations and deaths. Researchers will then be able to compare cancer registrations and deaths in the Bosnia group with a non-deployed group serving at the same time, controlling for age, sex and rank. By comparing to data from the original study (Unwin et al, 1999), researchers will be able to assess whether risk of cancer in the Bosnia cohort is related to reported exposures to potentially harmful materials during deployment.

The overall aim of the study is to compare the incidence of cancer in a cohort of UK armed forces personnel who deployed to Bosnia between 1992 and 1996 and a cohort of personnel who were in service at the time but did not deploy to Bosnia. Researchers will also compare the rate of cancer in the Bosnia group with that in the general UK population using publicly available national statistics of cancer and mortality. Additionally, it will be assessed whether the risk of cancer in the Bosnia group is associated with exposures to harmful materials during their deployment.

The specific research questions are:

1. Are individuals who served in Bosnia between 1992 and 1996 at greater risk of developing cancer than other military personnel who did not serve there?

2. Are individuals who served in Bosnia between 1992 and 1996 at greater risk of developing cancer than the general UK population?

3. Is risk of cancer in the Bosnia cohort related to self-reported exposures to potentially hazardous materials during deployment?

If it is found that military personnel who served on UN peacekeeping duties in Bosnia in 1992-1996 do not have higher than expected rates of cancer, the Ministry of Defence and the Service charities will have evidence to allay fears among this population that they are at increased risk.

If researchers find an association between serving in Bosnia and increased risk of certain cancers, heightened awareness among health service providers of this particular risk could lead to earlier diagnosis and improved quality of care. In addition, if researchers find an association between particular exposures and cancer, the Ministry Of Defence could act to protect personnel from such exposures in the future.

The pseudonymised data are required to be able to perform analyses described. The data is minimised to the cohort members within England & Wales, the research team have only requested fields required for the analysis.

King's College London are the sole data controllers for this research, decisions on how the data is processed are made by the substantive employees of King's College London. Data will only be accessed and processed by substantive employees of King's College London and will not be accessed or processed by any other third parties.

Funding

This study is supported by KCMHR internal funding.

Legal Basis

UK GDPR Article 6 (1) (e): This analysis is in the public interest since it seeks to provide important data which could inform treatment pathways for certain cancers and could inform decisions about particular patients within in the NHS.

UK GDPR Article 9 (2)(j): processing is necessary for scientific research purposes and shall be proportionate to the aim pursued, respect the right to data protection and provide for suitable and specific measures to safeguard the fundamental rights and the interests of the data subject. This data request is necessary to allow the study team to conduct analysis which supports the research objectives.

The key milestone is the decision on if there is sufficient data to carry out significant analysis immediately or whether there is a need to wait a few years until further data is available.

This is a long-term study recording the cancer status of veterans of The UK Armed Forces deployments to Bosnia between 1992 and 1996. In view of the anticipated long latency period between exposure and the appearance of cancers there may not be sufficient data yet to carry out the analysis.

Once a decision has been made that there is sufficient data it is expected that the outputs will include:

- a report of the findings from the study with recommendations to the UK Ministry of Defence (MoD) and to Service charities dealing with veterans and their families (for example, The Royal British Legion, SSAFA). The report will include a lay summary which can be made available on the webpages of the MoD and Service charities.

- an academic paper giving an analysis and discussion of the results of the study that, subject to acceptance, will be published in an appropriate journal such as the British Medical Journal (BMJ).

- an infographic will be produced which will be hosted on the King’s website and distributed to all stakeholders for onward dissemination.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

There are not yet any yielded benefits, the study team are waiting for the data to mature to realise the analysis from the study.

The data supplied by NHS Digital to King's Centre for Military Health Research (KCMHR) will be used only for the approved Medical Research Project MR795 - 'Cancer Risk & Mortality in a Sample of Service Personnel Deployed to Bosnia 1992 - 1996'. KCMHR is a research centre within King's College London (KCL).

Background:

There has been much speculation that military personnel who served on UN peacekeeping duties in Bosnia in 1992-1996 have higher than expected rates of cancer. This speculation has been based on individual case reports and some small clusters of leukaemia reported in Italian armed forces. It has been suggested that the allegedly higher rates of cancer are due to exposure to depleted uranium during deployment (Mayor, 2001). Other European nations have carried out studies to ascertain the incidence of cancer in their Bosnia veterans (Bogers et al, 2013; Gustavsson et al, 2004; Peragallo et al, 2010; Storm et al, 2006). In order to ascertain the rates of cancer and deaths in UK veterans who served in Bosnia, it is necessary to carry out systematic epidemiological studies and to date these have not been done. The study will determine whether the rates of cancer and death among personnel who served in Bosnia are higher than expected.

In 1997/8, using information provided by the Ministry of Defence (MoD), King’s College London (KCL) contacted members of UK Armed Forces who had deployed to Bosnia on UN peacekeeping duties as part of a larger study looking at the health consequences of the 1991 Gulf War. Data was collected using a questionnaire.

In 1997/8, KCMHR conducted a large epidemiological study on the health consequences of the 1990- 1991 Gulf War (Unwin et al, 1999). This involved identifying a cohort of 4250 individuals who had served in the Gulf, and two comparison groups: 4250 who had served on peace-keeping duties in Bosnia between 1992 and 1996, and 4250 individuals who were in the UK military at the time of the 1990-1991 Gulf War. In addition to demographic, health and service related data, environmental and combat related exposure data were collected from study responders.

In 2006, the Gulf War study team supplied personal data (name, date of birth, sex, NHS number, address) of participants in the Bosnia cohort of the 1997 KCL Gulf War study to the Office for National Statistics (ONS) so that participants could be traced and flagged. Self-reported data (and MoD provided data) relating to the Bosnia cohort have been retained as part of the KCL Gulf War study, with data relevant to addressing the aims of this additional sub-study held separately (the Bosnia study database).

Until 2014, the Bosnia study database held person identifying data along with cancer notifications and death registration details. On 27/03/2014, all directly identifying data had been removed from the Bosnia database, all hard copy notifications shredded and person identifying details deleted from notifications received electronically. Evidence of this was provided to NHS Digital. The Bosnia study data are pseudonymised. However, the personal data that relate the original KCL Gulf War study are still held at KCL (and will continue to be in anticipation of a possible follow up study). However, these data cannot be accessed by researchers from the Bosnia study.

In 2004 ethics committee approval was granted to ‘flag’ the Bosnia cohort with NHS Digital and to obtain cancer registration and death notifications (Joint SLAM/IOP NHS REC, study number 055/04). Section 60 of the Health & Social Care Act 2001 support was applied for and was granted in 2006 to supply patient identifiable data to NHS Digital, to flag the cohort and, for study responders, to supply death registration data, cancer registration data and exit information. For study non-responders summary tables for mortality and cancer incidence would be supplied at the end of the study. NHS Digital was provided with details of the Bosnia cohort (i.e. name, address, date of birth, and NHS number where available). A database of the study responders who were successfully flagged was compiled and is updated with details of cancer registrations and deaths as and when notifications are received from NHS Digital. In 2014 KCMHR again sought and received a favourable ethical review to continue to receive data from NHS Digital (REC reference 14/LO/1141, IRAS project ID 151260).

The immediate aim is to ascertain if the number of cancers and deaths reported so far would give sufficient power for meaningful analysis. Once researchers have the latest numbers of cancers and the number of deaths, a power calculation can be carried out to see if there is sufficient power (at least 80%) to show a clinically significant difference between the Bosnia group and a control group. Calculation showed that there were sufficient numbers to show a relative risk of 1.7 in the Bosnia cohort compared to the era group, in other words if there was an increased risk of cancer in the Bosnia cohort of 70% there would be sufficient power to detect it. That was based on the absolute risk of cancer reported by MacFarlane et al who found a low risk (0.5%) of cancer in the era group after 10 years. As time goes on, the absolute risk of cancer in both the era and Bosnia groups will increase (rates of cancers increase with age) so that after ~20 years it would be possible to detect a smaller increase in relative risk. There is not a specific number of cancers that would need to be reached in the Bosnia group since there may not actually be a difference in risk between the two groups. Of more importance is the length of time that needs to have elapsed since exposure for a possible difference in rate of cancer to have occurred. The latency period is the amount of time that elapses between initial exposure and the diagnosis of cancer. The latency period for blood related cancers e.g. non-Hodgkin lymphoma or myeloma have a shorter latency than solid tumours such as lung cancer. For example, the approximate latency period of lung cancer is approximately 14 years, of stomach cancer is 22 years and of kidney cancer is more than 40 years. It is now between 23 and 27 years since the Bosnia cohort deployed and this would be an appropriate time to assess whether the numbers of cancer notifications and /or deaths in this cohort compared to the era cohort show that there is an increased risk attributable to deployment to Bosnia.

If there have been sufficient occurrences KCMHR will not require further updates for the cohort.

For the longer term and main study aim KCMHR will ask the MoD to supply an anonymised dataset from the flagged “era group” containing information on age, sex, rank and cancer registrations and deaths. Researchers will then be able to compare cancer registrations and deaths in the Bosnia group with a non-deployed group serving at the same time, controlling for age, sex and rank. By comparing to data from the original study (Unwin et al, 1999), researchers will be able to assess whether risk of cancer in the Bosnia cohort is related to reported exposures to potentially harmful materials during deployment.

The overall aim of the study is to compare the incidence of cancer in a cohort of UK armed forces personnel who deployed to Bosnia between 1992 and 1996 and a cohort of personnel who were in service at the time but did not deploy to Bosnia. Researchers will also compare the rate of cancer in the Bosnia group with that in the general UK population using publicly available national statistics of cancer and mortality. Additionally, it will be assessed whether the risk of cancer in the Bosnia group is associated with exposures to harmful materials during their deployment.

The specific research questions are:

1. Are individuals who served in Bosnia between 1992 and 1996 at greater risk of developing cancer than other military personnel who did not serve there?

2. Are individuals who served in Bosnia between 1992 and 1996 at greater risk of developing cancer than the general UK population?

3. Is risk of cancer in the Bosnia cohort related to self-reported exposures to potentially hazardous materials during deployment?

If it is found that military personnel who served on UN peacekeeping duties in Bosnia in 1992-1996 do not have higher than expected rates of cancer, the Ministry of Defence and the Service charities will have evidence to allay fears among this population that they are at increased risk.

If researchers find an association between serving in Bosnia and increased risk of certain cancers, heightened awareness among health service providers of this particular risk could lead to earlier diagnosis and improved quality of care. In addition, if researchers find an association between particular exposures and cancer, the Ministry Of Defence could act to protect personnel from such exposures in the future.

The key milestone is the decision in if there is sufficient data to carry out significant analysis immediately or whether there is a need to wait a few years until further data is available.

This is a long term study recording the cancer status of veterans of The UK Armed Forces deployments to Bosnia between 1992 and 1996. In view of the anticipated long latency period between exposure and the appearance of cancers there may not be sufficient data yet to carry out the analysis.

Once a decision has been made that there is sufficient data the outputs will include:

- a report of the findings from the study with recommendations to the UK Ministry of Defence (MoD) and to Service charities dealing with veterans and their families (for example, The Royal British Legion, SSAFA). The report will include a lay summary which can be made available on the webpages of the MoD and Service charities.

- an academic paper giving an analysis and discussion of the results of the study that, subject to acceptance, will be published in an appropriate journal such as the BMJ.

- an infographic will be produced which will be hosted on the King’s website and distributed to all stakeholders for onward dissemination.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.

The data supplied by NHS Digital to King's Centre for Military Health Research (KCMHR) will be used only for the approved Medical Research Project MR795 - 'Cancer Risk & Mortality in a Sample of Service Personnel Deployed to Bosnia 1992 - 1996'. KCMHR is a research centre within King's College London (KCL).

Background:

There has been much speculation that military personnel who served on UN peacekeeping duties in Bosnia in 1992-1996 have higher than expected rates of cancer. This speculation has been based on individual case reports and some small clusters of leukaemia reported in Italian armed forces. It has been suggested that the allegedly higher rates of cancer are due to exposure to depleted uranium during deployment (Mayor, 2001). Other European nations have carried out studies to ascertain the incidence of cancer in their Bosnia veterans (Bogers et al, 2013; Gustavsson et al, 2004; Peragallo et al, 2010; Storm et al, 2006). In order to ascertain the rates of cancer and deaths in UK veterans who served in Bosnia, it is necessary to carry out systematic epidemiological studies and to date these have not been done. The study will determine whether the rates of cancer and death among personnel who served in Bosnia are higher than expected.

In 1997/8, using information provided by the Ministry of Defence (MoD), King’s College London (KCL) contacted members of UK Armed Forces who had deployed to Bosnia on UN peacekeeping duties as part of a larger study looking at the health consequences of the 1991 Gulf War. Data was collected using a questionnaire.

In 1997/8, KCMHR conducted a large epidemiological study on the health consequences of the 1990- 1991 Gulf War (Unwin et al, 1999). This involved identifying a cohort of 4250 individuals who had served in the Gulf, and two comparison groups: 4250 who had served on peace-keeping duties in Bosnia between 1992 and 1996, and 4250 individuals who were in the UK military at the time of the 1990-1991 Gulf War. In addition to demographic, health and service related data, environmental and combat related exposure data were collected from study responders.

In 2006, the Gulf War study team supplied personal data (name, date of birth, sex, NHS number, address) of participants in the Bosnia cohort of the 1997 KCL Gulf War study to the Office for National Statistics (ONS) so that participants could be traced and flagged. Self-reported data (and MoD provided data) relating to the Bosnia cohort have been retained as part of the KCL Gulf War study, with data relevant to addressing the aims of this additional sub-study held separately (the Bosnia study database).

Until 2014, the Bosnia study database held person identifying data along with cancer notifications and death registration details. On 27/03/2014, all directly identifying data had been removed from the Bosnia database, all hard copy notifications shredded and person identifying details deleted from notifications received electronically. Evidence of this was provided to NHS Digital. The Bosnia study data are pseudonymised. However, the personal data that relate the original KCL Gulf War study are still held at KCL (and will continue to be in anticipation of a possible follow up study). However, these data cannot be accessed by researchers from the Bosnia study.

In 2004 ethics committee approval was granted to ‘flag’ the Bosnia cohort with NHS Digital and to obtain cancer registration and death notifications (Joint SLAM/IOP NHS REC, study number 055/04). Section 60 of the Health & Social Care Act 2001 support was applied for and was granted in 2006 to supply patient identifiable data to NHS Digital, to flag the cohort and, for study responders, to supply death registration data, cancer registration data and exit information. For study non-responders summary tables for mortality and cancer incidence would be supplied at the end of the study. NHS Digital was provided with details of the Bosnia cohort (i.e. name, address, date of birth, and NHS number where available). A database of the study responders who were successfully flagged was compiled and is updated with details of cancer registrations and deaths as and when notifications are received from NHS Digital. In 2014 KCMHR again sought and received a favourable ethical review to continue to receive data from NHS Digital (REC reference 14/LO/1141, IRAS project ID 151260).

The immediate aim is to ascertain if the number of cancers and deaths reported so far would give sufficient power for meaningful analysis. Once researchers have the latest numbers of cancers and the number of deaths, a power calculation can be carried out to see if there is sufficient power (at least 80%) to show a clinically significant difference between the Bosnia group and a control group. Calculation showed that there were sufficient numbers to show a relative risk of 1.7 in the Bosnia cohort compared to the era group, in other words if there was an increased risk of cancer in the Bosnia cohort of 70% there would be sufficient power to detect it. That was based on the absolute risk of cancer reported by MacFarlane et al who found a low risk (0.5%) of cancer in the era group after 10 years. As time goes on, the absolute risk of cancer in both the era and Bosnia groups will increase (rates of cancers increase with age) so that after ~20 years it would be possible to detect a smaller increase in relative risk. There is not a specific number of cancers that would need to be reached in the Bosnia group since there may not actually be a difference in risk between the two groups. Of more importance is the length of time that needs to have elapsed since exposure for a possible difference in rate of cancer to have occurred. The latency period is the amount of time that elapses between initial exposure and the diagnosis of cancer. The latency period for blood related cancers e.g. non-Hodgkin lymphoma or myeloma have a shorter latency than solid tumours such as lung cancer. For example, the approximate latency period of lung cancer is approximately 14 years, of stomach cancer is 22 years and of kidney cancer is more than 40 years. It is now between 23 and 27 years since the Bosnia cohort deployed and this would be an appropriate time to assess whether the numbers of cancer notifications and /or deaths in this cohort compared to the era cohort show that there is an increased risk attributable to deployment to Bosnia.

If there have been sufficient occurrences KCMHR will not require further updates for the cohort.

For the longer term and main study aim KCMHR will ask the MoD to supply an anonymised dataset from the flagged “era group” containing information on age, sex, rank and cancer registrations and deaths. Researchers will then be able to compare cancer registrations and deaths in the Bosnia group with a non-deployed group serving at the same time, controlling for age, sex and rank. By comparing to data from the original study (Unwin et al, 1999), researchers will be able to assess whether risk of cancer in the Bosnia cohort is related to reported exposures to potentially harmful materials during deployment.

The overall aim of the study is to compare the incidence of cancer in a cohort of UK armed forces personnel who deployed to Bosnia between 1992 and 1996 and a cohort of personnel who were in service at the time but did not deploy to Bosnia. Researchers will also compare the rate of cancer in the Bosnia group with that in the general UK population using publicly available national statistics of cancer and mortality. Additionally, it will be assessed whether the risk of cancer in the Bosnia group is associated with exposures to harmful materials during their deployment.

The specific research questions are:

1. Are individuals who served in Bosnia between 1992 and 1996 at greater risk of developing cancer than other military personnel who did not serve there?

2. Are individuals who served in Bosnia between 1992 and 1996 at greater risk of developing cancer than the general UK population?

3. Is risk of cancer in the Bosnia cohort related to self-reported exposures to potentially hazardous materials during deployment?

If it is found that military personnel who served on UN peacekeeping duties in Bosnia in 1992-1996 do not have higher than expected rates of cancer, the Ministry of Defence and the Service charities will have evidence to allay fears among this population that they are at increased risk.

If researchers find an association between serving in Bosnia and increased risk of certain cancers, heightened awareness among health service providers of this particular risk could lead to earlier diagnosis and improved quality of care. In addition, if researchers find an association between particular exposures and cancer, the Ministry Of Defence could act to protect personnel from such exposures in the future.

The key milestone is the decision in if there is sufficient data to carry out significant analysis immediately or whether there is a need to wait a few years until further data is available.

This is a long term study recording the cancer status of veterans of The UK Armed Forces deployments to Bosnia between 1992 and 1996. In view of the anticipated long latency period between exposure and the appearance of cancers there may not be sufficient data yet to carry out the analysis.

Once a decision has been made that there is sufficient data the outputs will include:

- a report of the findings from the study with recommendations to the UK Ministry of Defence (MoD) and to Service charities dealing with veterans and their families (for example, The Royal British Legion, SSAFA). The report will include a lay summary which can be made available on the webpages of the MoD and Service charities.

- an academic paper giving an analysis and discussion of the results of the study that, subject to acceptance, will be published in an appropriate journal such as the BMJ.

- an infographic will be produced which will be hosted on the King’s website and distributed to all stakeholders for onward dissemination.

All outputs will contain only data that is aggregated with small numbers suppressed in line with the HES Analysis Guide.