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Excess body weight is associated with increased risk of colorectal cancer (CRC). However, it is currently not clear how weight loss strategies alter future CRC risk. Bariatric (or obesity) surgery (BS) is increasingly performed in individuals who are 'morbidly' obese (body mass index [BMI] >40 Kg/m2). A recent human mucosal biomarker study (Gut 2011;60;893-901) and a Swedish population-based epidemiological (BMJ, in review) study by the Applicants have both demonstrated that CRC risk actually increases with time after BS (in a cohort of 15095 individuals). Increased CRC risk was particularly evident greater than 10 yrs after BS (consistent with the natural history of CRC) and was similar for gastric bypass, gastric banding and gastroplasty. By contrast, CRC risk in non-operated obese individuals remained stable.
To confirm and extend (with individual BMI data and colorectal adenoma outcomes) the important (but counter-intuitive, in the presence of weight loss) finding from the Swedish population-based study that CRC risk actually increases after BS, by performing a larger British population study based on individual-level linkage of the Hospital Episode Statistics (HES) database, National Cancer Data Registry (NCDR) and General Practice Research Database (GPRD).
Ethically-approved database linkage will be performed using an established National Cancer Intelligence Network (NCIN) linkage approach in NYCRIS. HES data (NICE-utilised codes for BS [G30-33] or obesity alone [E66; ICD-10]) from 1997-2010 will be linked to NCDR data on CRC diagnosis, tumour location and stage at diagnosis until 2014. Separate linkage of NCDR data to the GPRD (covering approximately 5% of the population) will validate HES coding for the BS procedure or obesity alone for a subset of the study population. Where possible, we will use longitudinal BMI data from the GPRD to link changes in body weight over time with CRC risk. The GPRD will also allow us to investigate colorectal adenoma (polyp) risk after BS. The National Bariatric Surgery Register (NBSR) can not be used as it does not have approval for use of individual data. The risk of developing CRC will be compared between those who underwent BS and non-operated obese individuals. Incidence rates will be compared to the expected risk of developing CRC in the English population as a whole. The expected number of CRCs will be calculated for each cohort by multiplying the observed person-time by age, sex and calendar year-specific cancer incidence rates in the corresponding background population. Standardised incidence ratios will then be calculated. Person-years at risk in each cohort will be calculated from the date of entry into the study to the diagnosis of a cancer, death or the end of the study period (2014). HES data predict that, during the study period from 1997 until 2010, the BS cohort with greater than 10 year post-BS exposure will be approximately 6700 with an estimated 70 incident CRCs based on an age-standardised CRC rate of 50/100000/year and an age range of 40-60 years during follow-up (cf. 49 CRCs in the Swedish population study).
Confirmation that BS is associated with increased CRC risk has profound implications for CRC surveillance in an increasingly large population of BS patients world-wide. This work would prompt immediate evaluation of colonoscopy for colorectal adenoma detection and polypectomy in a newly defined risk group for CRC.
Obesity is an enormous global health problem. In addition to excess heart disease, diabetes and musculoskeletal disease, obesity also increases the risk of large bowel (also known as colorectal) cancer, as well as other common malignancies. The high number of people with excess body weight means that obesity has become a major risk factor for colorectal cancer (CRC) and is believed to be responsible for approximately 16% of all CRC in men in Europe. Obesity (or bariatric) surgery is increasingly used to treat obesity that is refractory to other treatment measures. There are considerable short-term benefits from surgery for heart disease and diabetes but long-term effects on cancer risk after obesity surgery are not well characterised. The Applicants have recently published results from an experimental study and a separate population-based study in Sweden that both suggest that CRC risk actually increases after obesity surgery, despite weight loss.
We propose to confirm and extend (also looking at the benign precursor of CRC called the adenoma or polyp) the findings from the Swedish study that CRC risk actually increases after obesity surgery. We will perform a larger British population study based on linking established hospital admission, cancer registry and general practice databases at an individual level.
Databases will be linked by the Northern & Yorkshire Cancer Registry Information Service based in Leeds using ethically-approved methods already established by the National Cancer Intelligence Network. Individuals identified as having had obesity surgery, or diagnosed with obesity with no prior obesity surgery, between 1997 and 2010 will be identified from a national hospital admission database (called HES). These cases will be linked to National Cancer Registry (NCDR) data on diagnosis and characteristics of CRC occurring until 2014. Separate linkage of the cancer registry data to a general practice database will validate the HES identification of patients and will also allow us to investigate colorectal adenoma risk after obesity surgery. The number of CRCs in patients who underwent obesity surgery and non-operated obese individuals will be compared to the expected risk of developing CRC in the English population as a whole. This will allow a value called the standardised incidence ratio to be calculated for direct comparison of the bariatric surgery and obese no surgery groups. Preliminary HES data predict that this English study will be 50% larger than the Swedish study.
It is vitally important that we confirm the somewhat controversial findings from our Swedish study using independent databases in another country. Confirmation that bariatric surgery is associated with increased CRC (and polyp) risk in the UK has profound implications for the need to monitor patients at future increased risk of CRC after obesity surgery. The work would prompt immediate evaluation of the need to undergo periodic optical bowel examination (called colonoscopy) for surveillance and prevention of CRC following obesity surgery.