Cohort Profile: The British Columbia Generations Project (BCGP)

The British Columbia Generations Project (BCGP) is a prospective, population-based cohort created in order to better understand the effects of environmental exposures, lifestyle and genetics on chronic diseases. Between 2009 and 2016, 29 850 British Columbians primarily between 35 and 69 years of age were recruited for the study. The cohort will be followed periodically for up to 50 years. Passive follow-up includes linkage to provincial cancer diagnoses and administrative health data. The current cohort size is 29 796. Data collected include: Health and lifestyle questionnaire: participants provided data on sociodemographics, lifestyle, medications and personal and family medical history at enrolment and several years later. Physical measures: anthropometric and physiological measurements were collected at enrolment. Biosamples: most participants donated a biosample (blood, urine). Genotyping: genotyping was conducted using the Affymetrix UK Biobank Axiom 2.0 gene chip platform. Blood measurements: standard biomarkers of cancer and inflammation were measured using BioRad’s Bio-Plex Pro™ Assay. Residential history questionnaire: participants reported the location, housing type, heating fuel, and water source of all residences over their lifetimes. For BCGP data and biosample access, see the BCGP website [https://www.bcgenerationsproject.ca/]. The British Columbia Generations Project (BCGP) is British Columbia’s (BC) largest, prospective, population-based cohort, health research databank and biobank.1 It was created in order to better understand the effects of environmental exposures, lifestyle and genetics on chronic diseases such as cancer. The resulting knowledge is intended to contribute to the development of new aetiological information leading to earlier disease detection and new prevention strategies. BCGP was approved by the University of British Columbia - British Columbia Cancer Agency Research Ethics Board. BCGP is also part of the pan-Canadian multi-centred Canadian Partnership for Tomorrow Project (CPTP).2 CPTP is a confederation of five regional cohorts, namely the Atlantic Partnership for Tomorrow’s Health (Nova Scotia, New Brunswick, Prince Edward Island, Newfoundland and Labrador), Alberta’s Tomorrow Project, the Ontario Health Study and Quebec’s CARTaGENE.3–5 CPTP was launched in 2008 with the mandate of collecting high-quality health data, physical measurements and biological specimens, constituting a research platform that can be accessed by researchers across Canada and internationally. Similar data collected across CPTP cohorts have been ‘harmonized’, i.e. converted into equivalent metrics, in order to ensure seamless integration of pooled regional cohort data. BCGP aimed to collect health information and biological samples from approximately 30 000 British Columbians, primarily between 35 and 69 years of age (refer to Supplementary material for further details, available as Supplementary data at IJE online). Between 2009 and 2013, BC residents were actively recruited through public outreach activities, using commercial mail directories, brochure distribution, media awareness campaigns and word-of-mouth referrals (Figure 1). Approximately 4% of the British Columbians in the required age range who could be contacted expressed interest in participating (29 850) (Figure 1). Schematic of BCGP cohort formation. Residents of BC, primarily between the ages of 35 and 69, were actively recruited to BCGP through various public outreach activities. Of the eligible individuals who could be contacted through these means, 4% consented to participating. The majority of the resulting 29 850 participants completed a baseline health and lifestyle questionnaire and donated blood and/or urine samples. After more than 8 years of follow-up, only 54 individuals have completely withdrawn from the study. The current update of the harmonized health and lifestyle questionnaire, which has comparable variables that can be pooled with other regional cohorts, has data from 28 825 participants. Although enrolment remained open until 2016, the majority of participants joined in the first few years of recruitment (Figure 2). Participation was fairly stable across British Columbia, with the majority of participants residing in highly populated regions of the province, such as the Lower Mainland and Vancouver Island (Figure 3). Many of these regions were also the sites of BCGP study assessment centres, which were located across BC for varying periods of time during enrolment (i.e. Vancouver, North Vancouver, Abbotsford, Coquitlam, Nanaimo, Victoria, Kamloops, Kelowna, Prince George). Number of participants recruited for BCGP from 2009 to 2016. Between 2009 and 2016, 29 850 BC residents, primarily between the ages of 35 and 69, were recruited for BCGP. The majority of participants joined between 2009 and 2012. The spikes in participation in 2009/early 2010 and in 2011–12 correspond to the establishment of the first study assessment centre and several satellite assessment centres, respectively. Biosamples (blood, urine) were collected at enrolment and during a participant outreach campaign in 2013–14. Approximate geographical distribution of BCGP participants based on self-reported postal code at enrolment. Participants reside across BC, predominantly in the Lower Mainland and on Vancouver Island. Participating regions tend to be highly populated and many are also the sites of study assessment centres (shown in photos). Only towns with at least five participants are displayed. BCCRC, BC Cancer Research Centre; DHCC, Gordon and Leslie Diamond Health Care Centre. At enrolment (baseline), participants were asked to complete a health and lifestyle questionnaire (HLQ) at an assessment centre and/or at home. HLQs were completed by 29 315 participants (Figure 1). Currently harmonized HLQ data from 28 825 BCGP participants are available. Also at enrolment, physiological measures were collected by BCGP study staff for the 56% of participants who chose to visit an assessment centre (Table 1). At a limited number of assessment centres, participants also had their blood collected by registered on-site phlebotomists or nurses. Most participants donated biosamples (blood, urine) at a participating community medical laboratory. Samples were shipped by community laboratoriess to BC Cancer and typically arrived by the following business day. Nearly 90% of BCGP participants provided a biosample at enrolment or during a participant outreach campaign in 2013–14. BCGP data QC, quality control. Numbers in the entire BCGP cohort (not limited to harmonized data except for baseline health and lifestyle questionnaire). BCGP data QC, quality control. Numbers in the entire BCGP cohort (not limited to harmonized data except for baseline health and lifestyle questionnaire). Participants consented to re-contact and follow-up. BCGP will continue to be followed periodically for up to 50 years, contingent on funding. Passive follow-up includes ongoing linkage to provincial administrative health data, such as medical claims to BC’s health insurance plan and cancer diagnoses captured by the BC Cancer Registry. Additional requests for participants to provide more information, biospecimens and/or physical measurements, also continue. In follow-up thus far, the majority of BCGP participants have continued to be active in the study, with approximately 75% of participants completing a residential history questionnaire (RHQ) in 2015–16 and/or a follow-up questionnaire to the baseline HLQ in 2016–17. Only a minority of participants have reduced their involvement in, or withdrawn from, the study since enrolment. More specifically, 1.8% passed away, 0.8% cannot be contacted and 1.5% have withdrawn and/or moved. These participants are somewhat older than the other BCGP participants who contributed to the harmonized HLQ dataset, with more than one-quarter being 65 years of age or older at enrolment (data not shown). They also tend to be male (40% versus 31%) and fewer have Bachelor’s degrees or higher. However, such differences are minor given the small proportion of the cohort they comprise. Furthermore, the majority of withdrawn individuals have permitted continued passive follow-up. Only 54 have requested complete withdrawal from the study, including removal of their previously collected data. This has resulted in data from 22 participants being removed from the harmonized HLQ dataset. Unless otherwise noted, analyses reported here are therefore restricted to the 28 825 BCGP participants whose data remain in the harmonized HLQ dataset (Table 1). At baseline, the HLQ was used to collect self-reported data on sociodemographics, lifestyle, medications and personal and family medical history. For participants who visited a study assessment centre at baseline, anthropometric measurements (height, weight, waist and hip circumferences) were collected by study staff. Otherwise, participants collected these values themselves and reported them in the HLQ. Additional physical measurements were also taken at assessment centres, including blood pressure, lung function, bone density, body fat percentage and grip strength (see Supplementary material, available as Supplementary data at IJE online). Before providing a biosample (i.e. blood, urine), participants completed a short sample donation questionnaire to record such factors as their dietary and health status at collection time (e.g. alcohol, caffeine or food consumption, recent chemotherapy or radiotherapy). The standard operating procedures for processing the biosamples can be found on the BCGP website [https://www.bcgenerationsproject.ca/researchers/bc-generations-project-open-access-biosample-information/]. Briefly, blood from each participant was collected in SST and EDTA vacutainers. ACD vacutainers were also used in approximately 60% of blood donations. For serum collection, two or three SST vacutainers were allowed to clot at room temperature for 30-60 min before being centrifuged at 1300-2200 g for 10 min at room temperature at the collection site. Three EDTA vacutainers were centrifuged for 10 min at 1300 g and 4°C, in order to separate plasma, white blood cells (buffy coat) and red blood cells. Whole blood from ACD tubes was frozen in a solution of RMPI/10%DMSO according to the UK Biobank protocol.6 All blood components were then aliquoted into cryovials. Spot urine samples were also transferred to cryovials. Long-term sample storage was either at -80°C (freezers) or -190°C (vapour phase liquid nitrogen freezers). The preanalytical conditions of the samples can be summarized using two reporting systems: Standard Preanalytical Coding (SPREC) for Biospecimens and the Biospecimen Reporting for Improved Study Quality recommendations.7,8 The seven-element-long SPREC codes summarize the type of sample, type of primary container, precentrifugation, centrifugation, second centrifugation, postcentrifugation delay and long-term storage conditions. These data are currently being harmonized with other CPTP data. In 2016–17, extracted DNA from a subset of 1000 participants was genotyped at regions of interest to disease research, using the Affymetrix UK Biobank Axiom 2.0 gene chip platform. This subset of participants had completed all baseline study activities, including answering the HLQ, having physical measures taken at an assessment centre and providing a blood sample. In addition, these participants reported being cancer-free at enrolment and being of White ethnicity. Standard biomarkers of cancer and inflammation were measured in plasma using BioRad’s Bio-Plex Pro™ Assay. The assay included the Human Cytokine 8-Plex Panel, which measures cytokines IL-2, IL-4, IL-6, IL-8, IL-10, GM-CSF, IFN-gamma and TNF-alpha, and the Human Acute Phase 4-Plex Panel, which measures the acute phase proteins 2-macroglobulin, C-reactive protein, haptoglobin and serum amyloid P. Also included was the Human Cancer Biomarker Panel 1, 16-Plex Panel, which measures the cancer biomarkers sEGFR, FGF-basic, G-CSF, follistatin, sHER-2/neu, HGF, sIL-6Ra, leptin, osteopontin, PDGF-AB/BB, PECAM-1, prolactin, SCF, sTIE-2, sVEGFR-1 and sVEGFR-2. The subsample tested comprised approximately 2000 participants (the 4-Plex tested 1300 approximately), 40 to 69 years of age, who were cancer-free at recruitment and were subsequently diagnosed with cancer within 7 to 48 months of donating blood to the study, as well as participants who reported two or three traits associated with metabolic syndrome (e.g. obesity, hypertension, diabetes) for HLQ. Age- and sex-matched controls without cancer or metabolic syndrome were also included. In order to understand how environmental exposures, such as housing type (single family, duplex, townhouse/row house, condo/apartment), heating fuel (electric, wood, gas, coal, oil) and water source (municipal, dug well, drilled well), affect health outcomes, participants were asked to complete the RHQ in 2015–16. Participants were requested to provide details on the aforementioned exposures, as well as the location (country, city) of all the residences in which they had lived for at least 1 year over their lifetimes. Street-level address, province and postal code were also collected for Canadian residences. As noted previously, participants were asked to give an update on their health and lifestyle by completing a follow-up questionnaire in 2016–17. The questionnaire was similar to the baseline HLQ, but also included questions on mental health, marijuana use and e-cigarette use. Participants have consented to linkage of their BCGP data to administrative health data. Annually the BC Cancer Registry identifies cancer diagnoses in the BCGP cohort, and vital statistics information provided by the BC Vital Statistics Agency. Population Data BC provides linkage of cohort participants to a number of administrative health datasets, including physician billings information. As in other longitudinal health studies, women and individuals with higher of up a proportion of the BCGP cohort with the (Table with the BC years, as in the in the BCGP cohort has an older distribution of individuals and more are than of White with as their only first and of Canadian or British are also in the BCGP all found in British Columbia are in the of of the BCGP cohort and the British (the 35 to 69 years of to BCGP questions were not except for first have been to participants not give a to not the or the not to For of not type of were into they up of the BCGP but is not limited and is not a separate in was therefore with and to For values with by of the BCGP It but is not limited other and other and and and BCGP not have a and were therefore with other in Also of of also or Canadian (i.e. and/or For of values with of reported by of the BCGP It but is not limited other in and the and are separate of in is not in BCGP. Canadian Health In order to BCGP and similar but variables are given in to the BC years. to are not asked status in status was asked with to a was as who reported being in the or was as who in a or and by family in the and at in time since 1 Although to was not asked in were as having that of British Columbians in age range are to also that are of of the BCGP cohort and the British (the 35 to 69 years of to BCGP questions were not except for first have been to participants not give a to not the or the not to For of not type of were into they up of the BCGP but is not limited and is not a separate in was therefore with and to For values with by of the BCGP It but is not limited other and other and and and BCGP not have a and were therefore with other in Also of of also or Canadian (i.e. and/or For of values with of reported by of the BCGP It but is not limited other in and the and are separate of in is not in BCGP. Canadian Health In order to BCGP and similar but variables are given in to the BC years. to are not asked status in status was asked with to a was as who reported being in the or was as who in a or and by family in the and at in time since 1 Although to was not asked in were as having that of British Columbians in age range are to also that are At enrolment, a proportion of BCGP participants reported having had various chronic including and syndrome with the BC of the age as in the Canadian Health In and were reported by similar of the two and blood was reported somewhat more in It be noted that on long-term conditions (i.e. diagnosed by a health that are to or have months or only cancer and blood were reported as conditions that the participant had as to conditions that the participant currently most of the BCGP cohort had or only of the in of self-reported chronic conditions at enrolment in the BCGP cohort and the British (the Canadian Health 35 to 69 years Although on long-term conditions (i.e. diagnosed by a health that are to or have months or only cancer and blood were reported as conditions that the participant as to conditions that the participant also asked the participant from the effects of BCGP asked the participant had a and were by was by BCGP. lung includes chronic and in BCGP between a of (i.e. was and (e.g. a participant only to be conditions they had (i.e. not conditions they had (i.e. and have been to the BC years. to participants not give a to not the or the not to of self-reported chronic conditions at enrolment in the BCGP cohort and the British (the Canadian Health 35 to 69 years Although on long-term conditions (i.e. diagnosed by a health that are to or have months or only cancer and blood were reported as conditions that the participant as to conditions that the participant also asked the participant from the effects of BCGP asked the participant had a and were by was by BCGP. lung includes chronic and in BCGP between a of (i.e. was and (e.g. a participant only to be conditions they had (i.e. not conditions they had (i.e. and have been to the BC years. to participants not give a to not the or the not to In and and were the with the British women and and were the most of age Similar were diagnosed in BCGP participants following enrolment, based on linkage to the BC Cancer Registry in (Table These also BCGP of they had been diagnosed with (data not shown). However, participants to cancer and lung cancer. It be noted that since the self-reported were than differences be to lung (i.e. In addition, have been self-reported as also not between and a with the BC Cancer Registry As is the for cancer the highly are not captured and are therefore by the BC Cancer Registry. of diagnosed in the BCGP cohort study enrolment as by linkage to the BC Cancer Registry in The are the cancer for the entire BCGP cohort (not limited to harmonized diagnosed study enrolment and available in the BC Cancer Registry as of the of linkage in complete up to from the participant are included. The number of blood samples collected to cancer (e.g. at are also of diagnosed in the BCGP cohort study enrolment as by linkage to the BC Cancer Registry in The are the cancer for the entire BCGP cohort (not limited to harmonized diagnosed study enrolment and available in the BC Cancer Registry as of the of linkage in complete up to from the participant are included. The number of blood samples collected to cancer (e.g. at are also As in the BCGP cohort current who are not to at home. Most more than a few a and five to of or or each day. The majority of BCGP participants are to for than on a or than on a during Although most in or of physical according to their Physical approximately of each are more than of have or only of the associated with these disease factors (i.e. three or fewer and of physical current or more BCGP lifestyle and range (i.e. standard have been to participants not give a to not the or the not to They have been from BCGP lifestyle and range (i.e. standard have been to participants not give a to not the or the not to They have been from Number of in the BCGP cohort are as having physical based on the Physical being a current a and of and day. Number of in the BCGP cohort are as having physical based on the Physical being a current a and of and day. self-reported body measurements are in More are with based on their body These metrics, as well as physical measurements, are in 8 for participants with harmonized HLQ data and harmonized physical measurements taken at assessment are similar between self-reported and anthropometric measurements and body waist and were measured and have been to participants not give a to not the or the not to body range (i.e. standard anthropometric measurements and body waist and were measured and have been to participants not give a to not the or the not to body range (i.e. standard Physical measurements at assessment centres restricted to participants with harmonized HLQ data and harmonized physical measurements data. body vital in of range (i.e. standard Physical measurements at assessment centres restricted to participants with harmonized HLQ data and harmonized physical measurements data. body vital in of range (i.e. standard number of have used BCGP and CPTP data to health For found that is not a for outcomes, such as hypertension, or using CPTP data. that have been approved to use BCGP data and resulting from use can be found on the BCGP website BCGP is through a linkage to population-based cancer and administrative health data Population Data In to BCGP has a of with approximately 90% of participants having donated physiological measurements were in more than of participants. BCGP have many of the and by studies, by collecting information Samples collected to a health can be requested for by research age namely year are also more to chronic conditions enrolment with and older with conditions. However, as the BCGP cohort to be more and includes more women than the BC that disease be than In addition, or individuals are strength of BCGP is that is within the pan-Canadian This the of health data from more than 000 across the as well as the of a of environmental exposures, and a sample size the study of and outcomes, as well as This has also the of and between the participating regional studies, and has harmonized available to researchers the of the of BCGP is to on the development and prevention of chronic diseases for other can to BCGP biosamples and the dataset, including genotyping and data, as on the BCGP website BCGP data to administrative health data be requested from Population Data BC Data to the BC Cancer Registry can be requested through the BCGP or through Population Data Additional information BCGP can be by of study has been through from the Canadian Partnership Cancer and by Health The expressed the of the and not the of Health BCGP has also been by BC Cancer and the BC Cancer to and This not have been without the of all BCGP participants. to current and BCGP including but not limited and to for also not have been to participants across the province without assessment centre staff and community BC The have of interest to

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