Study Protocol
Word count ( 2260 plus mentions )
1. Title
Dietary sugars and hazard of chest malignant neoplastic disease in the UK Women ‘s Cohort.
2. Background
Reports of relationships between dietetic sugars, and chest malignant neoplastic disease hazard have been conflicting in cohort surveies. However, “ the possibility remains that a diet high in sugars may increase chest malignant neoplastic disease hazard ” ( Gnagnarella et al. , 2008 ) . Evidence from surveies suggests that unnatural glucose metamorphosis may be of import in breast carcinogenesis ( Muti et al. , 2002 ) . It has been hypothesised that “ glucose and other factors related to glucose metamorphosis, such as insulin and insulin-like growth-factors may lend to breast malignant neoplastic disease development ” ( Muti et al. , 2002 ) . The plausible mechanism being that high consumption of sugars has been suggested to promote serum degrees of insulin-growth factor-1 and surveies show high insulin-growth factor-1 may increase chest malignant neoplastic disease hazard ( Romieu et al. , 2004 ) .
Some case-control surveies have shown an increased hazard for sugars and chest malignant neoplastic disease ( Muti et al. , 2002 ) . This survey design is more prone to remember prejudice ; therefore cohort surveies are potentially more dependable. Prospective cohort surveies that have explored the relationship between sugar and chest malignant neoplastic disease hazard are limited. Those that have been conducted have produced at odds grounds ( Wen et al. , 2009 ) . Researchers within this field have called for “ farther prospective surveies to look into this hypothesis ” ( Bradshaw et al. , 2009 ) .
The UK Women ‘s Cohort Study ( UKWCS ) has been designed to research the association between diet and disease ( Greenwood et al. , 2000 ) . This cohort is ideal as baseline and follow up information has been collected on consumption of nutrients high in natural and processed beginnings of sugars.
3. Hypothesis and Aims
Hypothesis
- That there is no direct association between dietetic consumption of sugars, and increased hazard of chest malignant neoplastic disease within the UK Women ‘s Cohort.
Purposes
- What is the consequence on consumption of entire sugar on hazard of chest malignant neoplastic disease within the UK Women ‘s Cohort?
- What is the consequence on consumption of sweet nutrients compared to saccharify from fruit on hazard of chest malignant neoplastic disease within the UK Women ‘s Cohort?
- What is the consequence on consumption of fruit sugar, and, sucrose, and the hazard of chest malignant neoplastic disease within the UK Women ‘s Cohort?
- What is the consequence on consumption of entire sugars, saccharose and fruit sugar, and hazard of chest malignant neoplastic disease for both pre and post-menopausal adult females within the UK Women ‘s Cohort?
- How does the survey comparison to other cohorts look intoing similar observations.
4. Methods & A ; Data Beginnings
Study Design
The UKWCS was created with the specific purpose to “ look into the long-run relationship between diet and wellness results and, in peculiar, tumor ‘s and circulative disease ” ( Cade et al. , 2004 ) .
This probe will utilize a prospective cohort analytic survey design to research associations between sugar, saccharose, and fructose and breast malignant neoplastic disease.
Cohort surveies are suited to research the long-run relationship between diet and malignant neoplastic disease as they track single ‘s overtime ( Cade et al. , 2007 ) . The UKWCS was constructed by Professor Janet Cade and co-workers and started in 1993. Case-control surveies have inferred an association between sugar consumption and chest malignant neoplastic disease ( Tavani et al. , 2006 ) . A recent cohort survey failed to happen a similar association when following participants up over a much longer clip period than a retrospective case-control survey ( Nielsen et al. , 2005 ) .
This undertaking is a little graduated table Masters Dissertation undertaking utilizing informations antecedently obtained from the UKWCS. All aggregation of information has been done by University of Leeds and provided in anon. signifier to the pupil to set about a research undertaking as portion entry for maestro ‘s grade.
Datas Beginnings
Choice of Participants & A ; Selection Criteria
The cohort was taken from respondents to a direct mail study by the World Cancer Research Fund ( WCRF ) . Women populating in England, Wales, and Scotland, were specifically targeted. 500,000 people responded to the study, 35,372 adult females met the standards for choice UKWCS ( Cade et al. , 2004 ) . This cohort is described by the writers as “ wellness witting with merely 11 % current tobacco users and 58 % taking dietetic addendums. 28 % of the participants reported to be vegetarian and 1 % vegan ” . ( Cade et al. , 2004 ) .
Womans aged 35-69 old ages who completed the original mail study were eligible for inclusion in the survey, n = 35,372. Information on around 600 variables was recorded from participants ; response rate for those mailed was 58 % out of 61,000.
Participants were specifically selected based on gender, mostly adult females were recruited as one of the malignant neoplastic diseases being investigated was breast malignant neoplastic disease and adult females are much more at hazard of this disease compared to the male population, merely 1 % of the male population are diagnosed with chest malignant neoplastic disease ( Dumitrescu and Cotarla, 2005 ) . A minimal age of 35 old ages was set and a upper limit of 69 in order to obtain adequate instances of malignant neoplastic disease in pre and station menopausal adult females. All recruits were voluntaries in the survey and could choose out at anytime.
The research workers collected baseline informations in 2 stages. Phase 1 took topographic point between 1995 and 1998 ; participants filled in lifestyle questionnaires and validated ( 217-item ) nutrient frequence questionnaires posted to each cohort. In 1999 to 2002, participants were sent a farther 4-day nutrient and imbibe weighed journal, a 1-day physical activity journal and a questionnaire relating to personal and familial dietary and medical history. Follow up information was collected at 5 old ages after baseline utilizing questionnaire and 4-day nutrient journal.
Health information was obtained on participants by entering disease history ICD-10 ( International Classification of Diseases, WHO 1990 ) . Table 1, Appendix C, lists wellness information obtained on the original cohort. The cohort was last updated on 1st January 2010 ; engagement rate on day of the month was 17 % .
Sample size from the WRCF mail study was used to obtain estimations for Numberss required for the cohort. This was based on informations from the cohort formation in 1989. Figures demonstrated that at 1-year follow up, a sample size would necessitate to include 30,000 participants would observe differences in malignant neoplastic disease enrollment. The writers projected “ after leting for participant consequence, staggered entry and clip slowdown. This sample size should hold about 80 % power to observe an consequence which should place about 550 instances of chest malignant neoplastic disease ” within the cohort sample of 35,372. ( Cade et al. , 2004 ) .
The FFQ generated alimentary consumptions after using mention criterion values from McCance & A ; Widdowson ‘s The Composition of Foods ( 5th Edition ) . Enough information is available to be able to analyze specific foods of involvement, entire sugar, and sugar from sweet nutrients, sucrose and fructose. Health information recorded at baseline is included as Appendix C, table 1.
Variables
The relationship between chest malignant neoplastic disease incidence rate ( outcome variable ) and exposure to entire sugars, saccharose and fruit sugar ( forecaster variable ) at 5-year follow up will be measured. Mean consumptions will be taken for each variable and compared between menopausal position and quintile of consumption.
Issues of concern
Appropriate clip demands to be considered for developing on statistical package, STATA for analysis of informations. Consideration besides needs to be given to analysis of informations required for University and this has been built into the timetable. Data sets for the cohort are sensitive hence need to be analysed in the University, this is being arranged at present. Consideration of work committednesss needs besides to be taken into history hence the timetable is considered flexible other than concluding day of the months for completion.
5. Ethical Considerations
Recruitment
Baseline human information was collected by Leeds University research squad the research workers besides contacted one hundred and 74 local research moralss commissions in order for permission to be granted for the baseline survey.
Consent
All participants in the survey had to give written consent to be contacted and for baseline and follow up informations to be obtained from participants. Transcripts of information sheets and consent signifiers have non been included in this protocol to guarantee patients can non be identified. Participants besides gave consent for informations to be collected in nutrient journal, questionnaires, and 5 old ages follow up. Health information on disease history, medicines, familial disease history, early life, adult females ‘s wellness. Datas on socio-demographic and socioeconomic features was collected including smoke and intoxicant ingestion. Biological samples of blood and buccal cells ( cheek cells ) were obtained from a sample of participants, 5343 buccal cell DNA ; 2589 blood samples.
Administration
Regulated by Ethical motives and Governance Framework, covered by Human Tissue Act, Data Protection Act, informations will be held at Leeds University by the immediate research squad in secure databases.
Student research workers will hold to subscribe confidentiality declarations and must be supervised by an appropriate member of staff to guarantee informations is used suitably. Datas used for pupil research undertakings has been made anon. .
6. Analysis of Datas
Data will be analyzed utilizing STATA 10. Datas from the cohort has collected sums of foods in “ gms per twenty-four hours calculated by multiplying frequence of ingestion of each nutrient group by the alimentary content of the indicated part size and summing all nutrients ” . ( Cade et al. , 2007 ) Nutrient composing was derived from UK nutrient composing tabular arraies to enable analysis of single alimentary consumption.
Cohort baseline features will be analysed showing mean and standard divergence for entire sample population baseline steps obtained. The statistical relationship between entire sugar consumption, entire consumption of saccharose and entire fructose consumption will be investigated utilizing Cox relative jeopardy arrested development. Predictor variables will be entire sugars, entire saccharose, and entire fructose consumption. Outcome variable will demand age on diagnosing of chest malignant neoplastic disease.
There are a figure of available Multivariate endurance analysis theoretical accounts utilizing metric and non-metric independent Variables. The advantage of the Cox relative jeopardy arrested development is it can be used when there is a demand to measure multiple co-variates on endurance ( Cleves et al. , 2008 ) , and is the most widely used multivariate method. It is easy to implement in STATA, works with a jeopardy theoretical account, and handily separates baseline jeopardy map from covariates ( Cleves et al. , 2008 ) . Cox can besides manage both uninterrupted and categorical forecaster variables wwithout cognizing baseline jeopardy Ho ( T ) , can still cipher coefficients for each covariate, and hence hazard ratio ( Margetts & A ; Nelson, 2008 ) . It besides assumes multiplicative hazard, the relative jeopardy premise ( Cleves et al. , 2008 ) .
Associations will be investigated for sugar consumption for pre and station menopausal position individually. This will be achieved by looking at a simple analysis theoretical account that adjusts for age and entire energy consumption for forecaster variables and be presented in a table screening mean and standard divergence food consumptions for entire sample by chest malignant neoplastic disease position. This is so malignant neoplastic disease instances can be compared between pre-menopausal and post-menopausal adult females. This can so be compared to the cohort paper by Nielson, et Al. ( 2005, pp. 124-129 ) who looked at a figure of different sugars in their cohort.
A 2nd theoretical account more complex theoretical account will be derived to diminish the opportunity of common confounding variables seen in this type of cohort dietetic analysis. The complex theoretical account will set for age, organic structure mass index, usage of unwritten preventive pill, current smoke position, intoxicant ingestion, usage of endocrine replacing therapy, physical activity, figure of kids, age of menarche, age at first birth, void para, entire energy consumption at baseline, instruction, societal economic position. Due to the graded sampling strategy within this analysis, persons will necessitate to be weighted in both theoretical accounts for the reverse chance of being sampled.
Sensitivity analysis will be used to except adult females who were diagnosed with chest malignant neoplastic disease in the first twelvemonth after finishing the FFQ. It will besides except persons with old malignant malignant neoplastic diseases. This has been done as participants with old instances of malignant neoplastic disease are at increased hazard therefore may bias any baseline step.
When information was originally collected by Cade, et Al ( 2004 ) a 2nd FFQ was taken from a sub sample of the cohort. This was done so the sum of random mistake could be “ estimated utilizing arrested development standardization attack ” . This allowed single predicted values of dietetic exposure for all participants.
Cox ‘s relative jeopardy arrested development will so be run utilizing the predicted values for each participant. Participants will be categorised into quintiles of alimentary consumption to give estimated hazard ratios. These will necessitate to be corrected for the effects of measuring mistake based on single nutrients in relation of diet to breast malignant neoplastic disease ( Cade, et al. , 2004 ) . The complex theoretical account will be presented in a tabular array so comparison between quintiles for pre-menopausal and post-menopausal cases/non instances, person-years of exposure, and showing jeopardy ratio ‘s with 95 % assurance intervals obtained from bootstrap estimations ( Cade, et al. , 2004 ) .
