Nội dung

Fowler et al. BMC Cancer (2020) 20:2 https://doi.org/10.1186/s12885-019-6472-9 RESEARCH ARTICLE Open Access Comorbidity prevalence among cancer patients: a population-based cohort study of four cancers Helen Fowler1* , Aurelien Belot1, Libby Ellis1, Camille Maringe1, Miguel Angel Luque-Fernandez2,3, Edmund Njeru Njagi1, Neal Navani4,5, Diana Sarfati6 and Bernard Rachet1 Abstract Background: The presence of comorbidity affects the care of cancer patients, many of whom are living with multiple comorbidities. The prevalence of cancer comorbidity, beyond summary metrics, is not well known. This study aims to estimate the prevalence of comorbid conditions among cancer patients in England, and describe the association between cancer comorbidity and socio-economic position, using population-based electronic health records. Methods: We linked England cancer registry records of patients diagnosed with cancer of the colon, rectum, lung or Hodgkin lymphoma between 2009 and 2013, with hospital admissions records. A comorbidity was any one of fourteen specific conditions, diagnosed during hospital admission up to 6 years prior to cancer diagnosis. We calculated the crude and age-sex adjusted prevalence of each condition, the frequency of multiple comorbidity combinations, and used logistic regression and multinomial logistic regression to estimate the adjusted odds of having each condition and the probability of having each condition as a single or one of multiple comorbidities, respectively, by cancer type. Results: Comorbidity was most prevalent in patients with lung cancer and least prevalent in Hodgkin lymphoma patients. Up to two-thirds of patients within each of the four cancer patient cohorts we studied had at least one comorbidity, and around half of the comorbid patients had multiple comorbidities. Our study highlighted common comorbid conditions among the cancer patient cohorts. In all four cohorts, the odds of having a comorbidity and the probability of multiple comorbidity were consistently highest in the most deprived cancer patients. Conclusions: Cancer healthcare guidelines may need to consider prominent comorbid conditions, particularly to benefit the prognosis of the most deprived patients who carry the greater burden of comorbidity. Insight into patterns of cancer comorbidity may inform further research into the influence of specific comorbidities on socio-economic inequalities in receipt of cancer treatment and in short-term mortality. Keywords: Cancer, Comorbidity, Multimorbidity, Deprivation, Prevalence, England, Epidemiology * Correspondence: Helen.Fowler@lshtm.ac.uk 1 Cancer Survival Group, Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Fowler et al. BMC Cancer (2020) 20:2 Background Comorbidity refers to the existence of a long-term health condition in the presence of a primary disease of interest [1]. Having one or more comorbidities may influence the patient’s prognosis for a primary disease such as cancer. Comorbidity may influence the timing of cancer diagnosis, in either a positive or a negative way. For example, the symptoms of comorbidity may drive a patient to seek medical care sooner, potentially leading to an earlier diagnosis. Alternatively, cancer symptoms may be mistakenly considered as symptoms of a pre-existing health condition, and could delay diagnosis [2–4]. Following diagnosis, the presence of comorbidity may also influence timing, receipt, or outcome of treatment, with clear evidence that those with comorbidity are less likely to receive curative treatment than those without, despite increasing evidence that many patients with comorbidity benefit from such treatment [3]. Although the presence of multiple co-existent health conditions is commonplace, the guidelines, funding and structures of primary care may not support the care of more patients with multiple conditions [5], and care in secondary and tertiary centres is typically highly siloed [3]. Methods used in the scientific literature to describe, measure and quantify the status of comorbidity as an explanatory factor in adverse disease outcomes are varied. Many summarised metrics of comorbidity have been proposed, providing an overall picture of a patient’s comorbidity status, some specific to a primary disease while others are more general. For example, a widely used metric of comorbidity in epidemiological studies is the Charlson Comorbidity Index (CCI) [6], which weights 19 long-term health conditions according to their relative risk of one-year mortality, to produce an overall index score. In this study, we firstly aimed to examine the prevalence of comorbid conditions in cancer patients using English population-based electronic health records of patients diagnosed with cancer of the colon, rectum, or lung or with Hodgkin lymphoma (HL). An association between comorbidity (not specific to any primary disease of interest) and socio-economic position has been widely reported: the prevalence of certain specific comorbid conditions [7–10] and general comorbidity prevalence being higher in deprived groups of patients [11–13]. Our second aim was to describe patterns of comorbidities and multiple comorbidity in these cancer patient cohorts, according to patient characteristics such as socioeconomic position (deprivation). Page 2 of 15 chronic obstructive pulmonary disease (COPD), rheumatological conditions, liver disease, diabetes, hemiplegia or paraplegia, renal disease, previous malignancy, obesity or hypertension. The conditions, selected following a systematic search of the data, included conditions of the Charlson Comorbidity Index [6] and any highly prevalent conditions that may influence cancer management alone or in combination with another condition. Data This study used England National Cancer Registry data of 331,655 patients aged 15–90 years at diagnosis with cancer of the colon, rectum, lung or Hodgkin’s lymphoma, between 2009 and 2013. Registry data provided information on patient sex, age at diagnosis, site of cancer, date of cancer diagnosis and area of residence at time of diagnosis, which was used to derive socio-economic position, based on deprivation quintiles of the Income Domain of the Indices of Multiple Deprivation [14]. The five-level, ordinal variable indicates the level of deprivation from 1 (least deprived) to 5 (most deprived). Areas of residence are defined at the Lower Super Output Area level (mean population 1500). Inpatient, outpatient and emergency hospital admissions records (Hospital Episode Statistics, HES) [15] were successfully linked with over 99% of the cancer registry records, using common unique variables present in both data sources. The International Statistical Classification of Diseases and Related Health Conditions tenth edition (ICD-10) [16] codes captured within the diagnostic fields of HES records provided information on health conditions recorded during hospital admissions. We used the ICD-10 code groupings of health conditions proposed by Quan and colleagues for defining comorbidities using administrative data (see Additional file 1) [17], and used an algorithm [18] to identify whether these conditions had been recorded in the six-year period prior to cancer diagnosis. In contrast to the approach of Maringe and colleagues [18], we included diagnoses of conditions recorded up to 6 months prior to cancer diagnosis. We anticipated that first-time diagnoses of the conditions could occur in this period, and wanted to obtain the most complete picture of patient comorbidity. We used cancer registry data to identify whether a patient had been diagnosed with an unrelated malignancy up to 6 years before their diagnosis with the cancer of interest. Descriptive data analysis Methods We defined a comorbid condition as one of the following fourteen health conditions: myocardial infarction (MI), congestive heart failure (CHF), peripheral vascular disease (PVD), cerebrovascular disease (CVD), dementia, We calculated the prevalence of a comorbid condition within each of the four patient cohorts defined by cancer site, firstly as a crude measure, calculating the percentage of patients who had a recorded diagnosis of the comorbidity in HES records, and secondly adjusting for Fowler et al. BMC Cancer (2020) 20:2 age and sex to account for the older age demographic of cancer patient populations. Weights for this adjustment were obtained from 2011 UK census published population estimates of persons living in England [19]. Statistical analysis Logistic regression models were used to estimate the odds ratio (OR) of having each comorbidity by cancer site, adjusting for sex, age at cancer diagnosis and deprivation group. The binary outcome variable indicated the presence of the comorbidity. To account for a non-linear association between increasing age and the presence of comorbidity, age was modelled as a continuous variable using a restricted cubic spline with one knot fixed at 70 years in analyses conducted for cancers of the colon, rectum and lung and at 45 years for HL (the knot position was chosen as to be close to the mean age of the patients in each of these cancer cohorts). To reduce the risk of unstable models, we ensured there were at least ten or more occurrences of a comorbidity within the specific cancer patient cohort for every parameter of the model (events per variable, EPV) [20]. Multinomial logistic regression was used to estimate the probability of having a given comorbidity, either in isolation, or as one of multiple comorbidities, according to cancer site. The three-category outcome variable indicated whether the patient did not have the given comorbidity, only had this comorbidity, or had this comorbidity with other comorbidities. Models were adjusted for age, sex and deprivation, and were run for each cancer site and comorbidity combination with at least ten EPV. All data analyses were conducted in STATA v.15.1 [21]. Results Patient characteristics The characteristics of patients diagnosed with cancer of the colon (N = 102,216), rectum (N = 56,342), lung (N = 165,677) or with HL (N = 7420) between 2009 and 2013, stratified by comorbidity status, are shown in Table 1. The majority of patients in each cohort were male: approximately 55% of colon, lung and HL patients and 63% of rectal cancer patients. At least 80% of colon, rectum and lung cancer patients were in the two oldest age group categories, while 50% of the HL patients were within the two youngest age groups. There was an even distribution of patients among each of the deprivation groups, except among lung cancer patients, where the percentage of patients in each group increased with deprivation level. Comorbidity was over twice as prevalent in lung cancer patients than in patients with HL: 67% of lung cancer patients had one or more comorbidities versus Page 3 of 15 almost 30% of HL patients. Similar patterns in comorbidity prevalence were seen in males and females. The prevalence of either single or multiple comorbidity rose with increasing age. Single comorbidity was more common than multiple comorbidity in the younger age groups, whereas in the older patients the opposite was observed. For example, approximately 29.2% of lung cancer patients aged 15–29 years had one comorbidity and 3.4% had multiple comorbidities, while in lung cancer patients aged 75–90 years the percentage of patients with one comorbidity or with multiple comorbidities were 26.9 and 49.9%, respectively. The prevalence of multiple comorbidity increased with deprivation level in colon, rectum and lung cancer patients, but there was no pattern with deprivation in HL patients or in the prevalence of one comorbidity. For example, from 24.7 to 25.7% of rectal cancer patients had one comorbidity, while 17.7 to 27.6% of patients had multiple comorbidities. Crude and adjusted prevalence of comorbidities at the time of cancer diagnosis Across all cancer patient cohorts, hypertension, COPD, diabetes, CVD, CHF and PVD were among the most commonly recorded comorbid conditions. Adjusting for age and sex strongly impacted the prevalence of some comorbid conditions in colon, rectum and lung cancer patients (Fig. 1). The three most prevalent comorbidities in all four cancer patient cohorts were hypertension, COPD and diabetes. The adjusted prevalence of hypertension and of diabetes was similar among patients in each of the four cohorts (approximately 15–20% of patients had hypertension while approximately 5% of patients had diabetes). However, the adjusted prevalence of COPD was markedly higher in patients with lung cancer: approximately 25% of lung cancer patients had COPD versus 10% of patients in the other patient cohorts. Similarly, in comparison between the four cohorts, the prevalence of several other conditions (CVD, CHF, PVD or previous malignancy) was highest among the lung cancer patients. Combinations of multiple comorbidity The relative frequency (%) in which five of the most common conditions (COPD, diabetes, CVD, CHF and PVD) are present either as a single comorbidity or in combination with ten other common comorbid conditions is shown in Fig. 2. For a given cancer (identified by colour), the denominator is the number of patients with the comorbid condition, as represented on the y-axis, and the numerator is the number of those patients who had the condition as a single comorbidity or who had another condition, as depicted by the x-axis. Patients Female 46.8 53.2 % 2666 11,971 42,166 44,644 30–44 45–59 60–74 75–90 43.7 41.3 11.7 2.6 0.8 21,591 19,940 15,651 3 4 Most deprived 15.3 19.5 21.1 22.1 21.9 % n % n % N % 67.1 2619 80.7 416 86.0 103 21.9 1317 15.6 99 13.4 5 0.7 207 1552 0.4 17.0 2.8 23.2 25,230 44.8 11.0 9597 3.7 5868 8118 9460 37.5 4394 40.7 5614 43.8 6123 10,484 46.3 6303 10,864 48.5 6331 28.1 5389 28.2 6208 28.4 6008 27.9 5836 28.2 5216 34.4 9225 16.4 31.1 11,266 20.0 27.8 11,750 20.9 25.8 12,222 21.7 23.3 11,879 21.1 13,251 29.7 13,931 31.2 17,462 39.1 19,756 35.1 20,696 49.1 11,696 27.7 9774 8035 2151 661 21,339 44.7 13,878 29.0 12,574 26.3 20,712 36.8 23,455 43.1 14,887 27.4 16,083 29.6 35,630 63.2 n 2+ % n 1 87.0 22 74.4 1635 83.9 203 4312 5646 6219 6810 6839 7128 46.7 2371 50.1 2838 52.9 2970 55.7 3031 57.6 2939 36.1 5868 14,073 55.8 6421 7143 1302 180 11,044 53.3 5299 18,782 52.7 8850 n 0 n 25.7 2542 25.2 2782 25.3 2561 24.8 2381 24.7 2101 29.7 6760 25.4 4736 17.0 819 13.1 47 10.6 5 25.6 4369 24.8 7998 % 2+ Number of patient comorbidities N 178 19,923 1757 27.6 42,158 24.7 39,220 21.8 32,822 19.5 28,411 17.7 23,066 34.2 68,734 18.8 75,085 8.5 3.0 2.4 21.1 74,109 22.4 91,568 % 25.4 23.7 19.8 17.1 13.9 41.5 45.3 12.0 1.1 0.1 44.7 55.3 % All patients Lung % n 1 % n 2+ % N % All patients 67.4 52 69.0 435 29.2 6 28.0 3581 24.8 110 3.4 2111 28.5 1660 22.4 18.0 1461 19.7 6.3 34.9 8025 37.2 6528 34.5 1339 18.0 28.5 12,477 38.0 1462 19.7 28.2 10,473 36.9 1428 19.2 28.3 7949 10.6 12,156 28.8 12,016 28.5 17,986 42.7 1573 21.2 12,356 31.5 10,885 27.8 15,979 40.7 1618 21.8 10,980 33.5 9365 9913 8589 15,921 23.2 18,517 26.9 34,296 49.9 790 25,973 34.6 22,241 29.6 26,871 35.8 1398 18.8 10,768 54.0 5574 1212 120 24,661 33.3 21,536 29.1 27,912 37.7 3257 43.9 % n 1 73.2 217 33.5 217 46.6 366 1071 68.1 291 1132 70.0 277 1018 69.6 263 1013 70.9 222 980 265 651 1001 68.5 288 1412 85.1 194 1885 89.3 205 2307 70.8 573 2907 69.8 697 n 0 n 2+ % 21 1.0 3.3 18.5 211 13.4 17.1 209 12.9 18.0 181 12.4 15.5 193 13.5 16.2 142 10.6 27.5 308 39.0 26.2 381 27.3 19.7 172 11.8 11.7 54 9.7 17.6 377 11.6 16.7 559 13.4 % Number of patient comorbidities Hodgkin lymphoma 29,333 32.0 25,283 27.6 36,952 40.4 4163 56.1 n 0 Number of patient comorbidities Abbreviations - IMD Indices of Multiple Deprivation 102,216 100.0 44,794 43.8 28,765 28.1 28,657 28.0 56,342 100.0 29,826 52.9 14,149 25.1 12,367 21.9 165,677 100.0 53,994 32.6 46,819 28.3 64,864 39.2 7420 100.0 5214 70.3 1270 17.1 936 12.6 22,623 2 TOTAL 22,411 Least deprived Deprivation group (IMD income) 769 15–29 Age at cancer diagnosis (years) 54,425 47,791 Male Sex N 1 All patients 0 Rectum All patients Number of patient comorbidities Colon Cancer Table 1 Patient characteristics according to comorbidity status, by cancer Fowler et al. BMC Cancer (2020) 20:2 Page 4 of 15 Fowler et al. BMC Cancer (2020) 20:2 Page 5 of 15 Rectum Colon 40 40 35 35 30 30 25 % 20 % 20 15 15 10 10 5 5 25 0 0 1 2 3 4 5 6 7 8 9 1 10 11 12 13 14 2 3 4 5 6 7 8 9 10 11 12 13 14 Adjusted Adjusted 95%CIs Hodgkin lymphoma Lung 40 35 35 30 30 25 25 % Crude 40 20 % 20 15 15 10 10 5 5 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1: Liver disease; 2: Previous malignancy; 3: Diabetes; 4: Obesity; 5: Dementia; 6: Hemi / Paraplegia; 7: CVD; 8: Hypertension; 9: Renal disease; 10: MI; 11: COPD; 12: CHF; 13: PVD; 14: Rheumatological conditions Fig. 1 Crude and adjusted prevalence (%) of fourteen comorbidities among cancer patients in England, by cancer with two or more of the x-axis conditions are represented in the numerator for each condition. Approximately one third of colorectal and lung cancer patients with COPD, and over half of HL patients with COPD, had this condition as a single comorbidity. By comparison, under one fifth of patients with diabetes, CVD, CHF and PVD had these conditions as a single comorbidity. CHF was the condition least frequently observed as a single comorbidity across all four cancer sites (89% or more of patients with CHF had additional comorbidities). Hypertension was the condition most commonly present with each of comorbidities for which cross tabulations were investigated. In each of the cancer cohorts, approximately three-quarters of patients with CHF, and a similar proportion with CVD, also had hypertension. COPD was most commonly seen in combination with diabetes, CVD, CHF or PVD in lung cancer patients: while over 50% of lung cancer patients with CHF also had COPD, around one third of patients with HL, colon or rectal cancers with CHF also had COPD. Multivariate analysis The odds ratios derived from logistic regression of each comorbid condition being present at the time of cancer diagnosis, by cancer site, for females relative to males, age (relative to age 70 in colon, rectal and lung cancer patients, and relative to age 45 in HL patients) and increasing deprivation, adjusted for the other listed variables, are shown in Table 2. Analyses conducted for patients with HL were restricted to the comorbidities of diabetes, hypertension and COPD, as the prevalence counts of the other conditions did not adhere to the minimum of ten EPV required for the analyses. Female patients with colon, rectal or lung cancer had up to 29% increased adjusted odds of having dementia (rectal cancer: OR 1.29; 95%CI 1.13, 1.48), up to 34% increased adjusted odds of having a previous malignancy (rectal cancer: OR 1.34; 1.23, 1.47) and approximately twice the adjusted odds of having rheumatological conditions (colon cancer: OR 2.16; 1.98, 2.36) compared to male patients. Conversely, compared with male patients in their respective cohort, females had significantly reduced adjusted odds of having diabetes, hemiplegia or Fowler et al. BMC Cancer (2020) 20:2 Page 6 of 15 Fig. 2 Relative frequency (%) of five common conditions as a single comorbidity or with another comorbidity, by cancer paraplegia, CVD, renal disease, MI, CHF or PVD. Across all four cancer cohorts, female patients had up to 38% reduced odds of having diabetes (HL: OR 0.62; 95%CI 0.50, 0.77). The adjusted odds of dementia, CVD, hypertension, renal disease, MI and CHF being present at diagnosis consistently increased with age. For example, with 70year old patients as the reference, colon cancer patients aged 45 had 87% reduced adjusted odds of CVD (OR 0.13; 0.13, 0.13) and 88% reduced adjusted odds of CHF (OR 0.12; 0.12, 0.12), while 90-year old patients had over three times the adjusted odds of CVD (OR 3.27; 2.69, 3.99) and over four times the adjusted odds of CHF (OR 4.72; 3.63, 6.13). There was no trend with age in colon, rectal or lung cancer patients for liver disease, having had a previous malignancy, diabetes or obesity. In lung cancer patients, no trend was observed with age for having COPD. For at least eleven of the fourteen conditions, the adjusted odds of having the comorbid condition increased with the level of deprivation in colon, rectal or lung cancer patients. Obesity, dementia, hemiplegia, CVD, hypertension, renal disease, MI, COPD, CHF and PVD were associated with deprivation level in all three cancer cohorts. For example, the most deprived groups of lung cancer and colon cancer patients had approximately twice the adjusted odds of having COPD compared with the least deprived groups (OR 1.96; 1.89, 2.03 and OR 2.01; 1.89, 2.12 in the most deprived patients with lung or colon cancer, respectively). No trend with deprivation was seen with rheumatological conditions or with having a previous malignancy. Probability of having single or multiple comorbidity at the time of cancer diagnosis The graphs depicted in Fig. 3 show the adjusted probability of patients having one of the nine most common comorbid conditions recorded (hypertension, COPD, diabetes, CHF, CVD, PVD, MI, obesity or rheumatological conditions) at the time of colon cancer diagnosis, either as a single comorbidity, or as one of multiple comorbidities, according to age at cancer diagnosis and deprivation group (the least and most deprived groups), as derived from multinomial logistic regression. With the exception of COPD, there was little difference between the most and least deprived groups in the probability of having each of the conditions as a single comorbidity. Among those patients with COPD as a single comorbidity, the difference in probability between 0.99 1.23 (0.91, 1.07) (1.16, 1.32) Female 1.10 1.03 (0.96, 1.25) (0.93, 1.14) 1.13 0.99 (0.99, 1.29) (0.89, 1.09) 1.38 1.03 (1.22, 1.58) (0.93, 1.15) 1.50 1.13 (1.31, 1.71) (1.02, 1.26) 2 3 4 Most deprived 1.00 1.00 Least deprived [REF] Deprivation group 0.91 0.71 (0.88, 0.94) (0.68, 0.75) 90 1.00 1.00 1.01 1.05 (0.98, 1.05) (0.97, 1.12) 80 1.13 0.74 (1.08, 1.17) (0.70, 0.78) 60 70 [REF] 1.18 0.40 (1.13, 1.23) (0.39, 0.41) 45 Age at cancer diagnosis (years) 1.00 1.00 Colon cancer Male [REF] Sex Previous malignancy OR (95% CIs) Liver disease 1.00 Obesity 1.00 Dementia 1.00 1.00 1.49 (1.46, 1.53) 1.00 0.65 (0.65, 0.66) 0.39 (0.38, 0.39) 0.70 (0.62, 0.79) 1.00 Hemi- or paraplegia 1.00 1.00 1.75 1.91 1.70 (1.64, 1.87) (1.68, 2.16) (1.47, 1.97) 1.48 1.73 1.42 (1.39, 1.58) (1.53, 1.95) (1.23, 1.63) 1.25 1.56 1.29 (1.18, 1.33) (1.38, 1.76) (1.11, 1.48) 1.12 1.09 1.19 (1.05, 1.19) (0.95, 1.24) (1.03, 1.37) 1.00 2.29 (1.88, 2.79) 1.47 (1.20, 1.80) 1.47 (1.20, 1.79) 1.25 (1.02, 1.54) 1.00 0.82 0.17 13.95 1.42 (0.69, 0.98) (0.17, 0.17) (12.35, 15.75) (1.39, 1.45) 1.31 0.74 4.68 (1.00, 1.71) (0.72, 0.77) (4.49, 4.89) 1.00 0.64 1.00 0.18 (0.55, 0.73) (0.95, 1.05) (0.17, 0.18) 0.27 0.79 0.02 (0.25, 0.29) (0.76, 0.82) (0.02, 0.02) 0.72 0.94 1.19 (0.69, 0.75) (0.87, 1.01) (1.09, 1.30) 1.00 Diabetes 1.00 Hypertension 1.00 1.00 1.60 1.54 (1.46, 1.76) (1.47, 1.61) 1.35 1.32 (1.23, 1.47) (1.27, 1.38) 1.20 1.18 (1.09, 1.31) (1.13, 1.23) 1.11 1.08 (1.01, 1.21) (1.03, 1.12) 1.00 3.27 2.13 (2.69, 3.99) (0.72, 6.26) 2.04 1.88 (1.80, 2.32) (0.68, 5.21) 1.00 0.46 0.51 (0.45, 0.47) (0.33, 0.80) 0.13 0.14 (0.13, 0.13) (0.12, 0.16) 0.80 0.90 (0.75, 0.85) (0.87, 0.92) 1.00 CVD Table 2 Odds ratios of condition being present, by cancer (adjusted for other listed variables) 1.00 MI 1.00 COPD 1.00 CHF 1.00 PVD 1.00 Rheum. conditions 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.83 1.55 2.01 1.67 1.59 0.99 (1.67, 2.01) (1.40, 1.72) (1.89, 2.12) (1.52, 1.83) (1.42, 1.76) (0.86, 1.14) 1.55 1.33 1.56 1.38 1.38 1.00 (1.42, 1.69) (1.21, 1.47) (1.47, 1.65) (1.26, 1.50) (1.25, 1.53) (0.88, 1.14) 1.34 1.21 1.24 1.16 1.26 0.95 (1.23, 1.47) (1.10, 1.34) (1.18, 1.32) (1.06, 1.27) (1.14, 1.40) (0.84, 1.08) 1.20 1.09 1.12 1.07 1.11 1.08 (1.09, 1.31) (0.99, 1.21) (1.06, 1.18) (0.98, 1.17) (1.00, 1.24) (0.96, 1.23) 1.00 4.35 2.26 1.04 4.72 1.70 1.31 (3.50, 5.40) (1.92, 2.65) (0.84, 1.29) (3.63, 6.13) (1.52, 1.91) (1.27, 1.36) 2.64 1.60 1.38 2.43 1.88 1.64 (2.30, 3.03) (1.42, 1.80) (1.05, 1.80) (2.10, 2.80) (1.66, 2.13) (1.58, 1.71) 1.00 0.41 0.52 0.72 0.45 0.43 0.54 (0.40, 0.42) (0.50, 0.54) (0.62, 0.83) (0.43, 0.46) (0.41, 0.44) (0.53, 0.55) 0.15 0.12 0.55 0.12 0.12 0.22 (0.15, 0.15) (0.11, 0.12) (0.49, 0.62) (0.12, 0.12) (0.12, 0.13) (0.22, 0.22) 0.75 0.48 1.05 0.66 0.45 2.16 (0.71, 0.80) (0.45, 0.51) (1.01, 1.09) (0.63, 0.70) (0.42, 0.48) (1.98, 2.36) 1.00 Renal disease Fowler et al. BMC Cancer (2020) 20:2 Page 7 of 15 1.05 1.34 (0.91, 1.22) (1.23, 1.47) Female 1.00 1.08 (0.77, 1.28) (0.94, 1.24) 1.50 0.91 (1.19, 1.89) (0.79, 1.05) 1.33 1.01 (1.05, 1.69) (0.88, 1.17) 1.77 1.14 (1.39, 2.24) (0.99, 1.33) 2 3 4 Most deprived 1.00 1.00 Least deprived [REF] Deprivation group 1.11 0.96 (1.09, 1.13) (0.90, 1.02) 90 1.00 1.00 0.98 1.22 (0.96, 1.00) (1.13, 1.32) 80 1.00 0.68 (0.98, 1.02) (0.65, 0.71) 60 70 [REF] 0.93 0.42 (0.91, 0.95) (0.41, 0.43) 45 Age at cancer diagnosis (years) 1.00 1.00 Rectal cancer Male [REF] Sex Previous malignancy OR (95% CIs) Liver disease 1.00 Obesity 1.00 Dementia 1.00 1.00 1.83 (1.81, 1.86) 1.00 0.60 (0.60, 0.60) 0.39 (0.39, 0.40) 0.66 (0.54, 0.81) 1.00 Hemi- or paraplegia 1.00 1.00 1.80 1.80 1.63 (1.63, 1.97) (1.48, 2.18) (1.31, 2.02) 1.60 1.63 1.30 (1.46, 1.75) (1.35, 1.97) (1.05, 1.60) 1.29 1.27 1.21 (1.18, 1.42) (1.04, 1.54) (0.98, 1.50) 1.14 1.28 1.10 (1.04, 1.26) (1.06, 1.56) (0.89, 1.37) 1.00 2.66 (1.89, 3.74) 2.23 (1.59, 3.12) 2.13 (1.52, 2.98) 1.70 (1.20, 2.40) 1.00 0.83 0.17 13.80 1.82 (0.72, 0.95) (0.17, 0.17) (12.36, 15.40) (1.79, 1.85) 1.37 0.73 5.57 (1.11, 1.71) (0.71, 0.74) (5.32, 5.84) 1.00 0.60 0.95 0.21 (0.54, 0.66) (0.92, 0.98) (0.21, 0.21) 0.27 0.69 0.06 (0.26, 0.29) (0.68, 0.71) (0.06, 0.06) 0.80 1.17 1.29 (0.75, 0.85) (1.04, 1.32) (1.13, 1.48) 1.00 Diabetes 1.00 Hypertension 1.00 1.00 1.78 1.48 (1.54, 2.05) (1.39, 1.57) 1.51 1.26 (1.32, 1.74) (1.19, 1.34) 1.39 1.14 (1.21, 1.60) (1.07, 1.20) 1.13 1.04 (0.98, 1.30) (0.99, 1.10) 1.00 4.07 2.51 (3.35, 4.94) (0.86, 7.29) 2.14 1.74 (1.92, 2.39) (0.71, 4.22) 1.00 0.46 0.49 (0.45, 0.47) (0.34, 0.71) 0.12 0.13 (0.12, 0.12) (0.12, 0.15) 0.75 0.95 (0.69, 0.82) (0.91, 0.99) 1.00 CVD Table 2 Odds ratios of condition being present, by cancer (adjusted for other listed variables) (Continued) 1.00 MI 1.00 COPD 1.00 CHF 1.00 PVD 1.00 Rheum. conditions 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.57 1.52 2.25 1.65 1.59 1.24 (1.34, 1.83) (1.30, 1.77) (2.07, 2.46) (1.42, 1.91) (1.36, 1.87) (1.00, 1.54) 1.34 1.33 1.62 1.25 1.34 1.12 (1.15, 1.55) (1.14, 1.54) (1.49, 1.76) (1.07, 1.44) (1.14, 1.57) (0.91, 1.38) 1.26 1.17 1.36 1.23 1.11 1.13 (1.08, 1.46) (1.00, 1.36) (1.25, 1.49) (1.06, 1.42) (0.94, 1.30) (0.92, 1.39) 1.06 1.06 1.14 1.11 1.06 1.09 (0.91, 1.24) (0.91, 1.24) (1.04, 1.25) (0.95, 1.29) (0.90, 1.24) (0.89, 1.34) 1.00 5.14 2.06 1.29 4.96 2.24 1.91 (4.22, 6.26) (1.82, 2.32) (1.06, 1.58) (4.04, 6.10) (1.97, 2.54) (1.84, 1.99) 2.61 1.63 1.46 2.46 1.80 1.65 (2.35, 2.90) (1.48, 1.80) (1.17, 1.83) (2.21, 2.74) (1.62, 1.99) (1.60, 1.70) 1.00 0.37 0.49 0.66 0.44 0.40 0.58 (0.36, 0.37) (0.48, 0.51) (0.59, 0.74) (0.43, 0.44) (0.39, 0.41) (0.57, 0.59) 0.12 0.11 0.47 0.12 0.07 0.30 (0.12, 0.13) (0.11, 0.11) (0.43, 0.51) (0.12, 0.12) (0.07, 0.07) (0.29, 0.30) 0.73 0.52 1.03 0.72 0.39 1.97 (0.66, 0.80) (0.46, 0.58) (0.97, 1.09) (0.65, 0.79) (0.34, 0.44) (1.73, 2.25) 1.00 Renal disease Fowler et al. BMC Cancer (2020) 20:2 Page 8 of 15 0.87 1.11 (0.82, 0.93) (1.06, 1.16) Female 1.28 0.95 (1.13, 1.46) (0.87, 1.03) 1.29 0.89 (1.14, 1.47) (0.82, 0.96) 1.44 0.84 (1.27, 1.62) (0.78, 0.91) 1.66 0.88 (1.48, 1.87) (0.81, 0.95) 2 3 4 Most deprived 1.00 1.00 Least deprived [REF] Deprivation group 0.54 0.76 (0.53, 0.55) (0.71, 0.82) 90 1.00 1.00 0.80 1.02 (0.78, 0.82) (0.92, 1.12) 80 1.35 0.93 (1.29, 1.42) (0.85, 1.01) 60 70 [REF] 1.42 0.83 (1.35, 1.49) (0.76, 0.89) 45 Age at cancer diagnosis (years) 1.00 1.00 Lung cancer Male [REF] Sex Previous malignancy OR (95% CIs) Liver disease 1.00 Obesity 1.00 Dementia 1.00 1.00 1.10 (1.07, 1.12) 1.00 0.75 (0.74, 0.76) 0.43 (0.43, 0.43) 0.81 (0.75, 0.88) 1.00 Hemi- or paraplegia 1.00 1.00 1.29 1.69 1.52 (1.23, 1.36) (1.50, 1.90) (1.37, 1.69) 1.25 1.51 1.38 (1.18, 1.32) (1.34, 1.70) (1.24, 1.53) 1.09 1.27 1.21 (1.03, 1.15) (1.12, 1.45) (1.09, 1.36) 1.10 1.19 1.13 (1.04, 1.16) (1.05, 1.36) (1.01, 1.27) 1.00 2.17 (1.88, 2.52) 1.76 (1.51, 2.04) 1.50 (1.28, 1.76) 1.38 (1.17, 1.62) 1.00 0.82 0.18 13.22 1.23 (0.68, 0.99) (0.18, 0.18) (11.20, 15.60) (1.20, 1.27) 1.24 0.67 4.37 (0.95, 1.63) (0.65, 0.69) (4.13, 4.63) 1.00 0.60 0.97 0.28 (0.52, 0.69) (0.93, 1.00) (0.28, 0.28) 0.24 0.70 0.04 (0.23, 0.26) (0.68, 0.71) (0.04, 0.04) 0.75 1.12 1.22 (0.73, 0.78) (1.05, 1.20) (1.15, 1.30) 1.00 Diabetes 1.00 Hypertension 1.00 1.00 1.45 1.22 (1.36, 1.54) (1.18, 1.27) 1.36 1.13 (1.27, 1.45) (1.09, 1.17) 1.20 1.04 (1.12, 1.28) (1.01, 1.08) 1.09 1.02 (1.01, 1.17) (0.98, 1.05) 1.00 2.26 1.70 (1.77, 2.88) (0.59, 4.85) 1.56 1.59 (1.31, 1.85) (0.57, 4.41) 1.00 0.55 0.49 (0.52, 0.59) (0.30, 0.80) 0.22 0.12 (0.21, 0.23) (0.11, 0.14) 0.83 0.98 (0.80, 0.87) (0.96, 1.00) 1.00 CVD Table 2 Odds ratios of condition being present, by cancer (adjusted for other listed variables) (Continued) 1.00 MI 1.00 COPD 1.00 CHF 1.00 PVD 1.00 Rheum. conditions 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.33 1.33 1.96 1.35 1.32 1.05 (1.24, 1.43) (1.24, 1.43) (1.89, 2.03) (1.26, 1.44) (1.24, 1.41) (0.96, 1.14) 1.21 1.28 1.59 1.30 1.17 1.08 (1.13, 1.30) (1.19, 1.38) (1.53, 1.65) (1.22, 1.39) (1.10, 1.25) (0.99, 1.18) 1.15 1.16 1.36 1.15 1.14 1.04 (1.07, 1.24) (1.08, 1.25) (1.31, 1.41) (1.07, 1.23) (1.07, 1.21) (0.95, 1.14) 1.07 1.08 1.17 1.11 1.12 1.09 (1.00, 1.16) (1.00, 1.17) (1.12, 1.22) (1.03, 1.19) (1.05, 1.20) (0.99, 1.20) 1.00 4.16 1.51 0.80 3.55 1.08 0.92 (3.13, 5.53) (1.28, 1.78) (0.51, 1.24) (2.63, 4.79) (0.90, 1.30) (0.88, 0.96) 2.48 1.38 1.10 1.93 1.47 1.07 (2.07, 2.97) (1.19, 1.61) (0.63, 1.94) (1.62, 2.29) (1.15, 1.87) (1.02, 1.13) 1.00 0.38 0.62 0.69 0.47 0.47 0.70 (0.36, 0.39) (0.58, 0.66) (0.47, 1.03) (0.45, 0.50) (0.43, 0.51) (0.68, 0.73) 0.13 0.19 0.39 0.16 0.10 0.29 (0.13, 0.13) (0.19, 0.20) (0.31, 0.50) (0.16, 0.17) (0.09, 0.10) (0.28, 0.29) 0.72 0.60 1.09 0.76 0.50 1.98 (0.69, 0.75) (0.58, 0.63) (1.07, 1.11) (0.73, 0.80) (0.48, 0.52) (1.87, 2.09) 1.00 Renal disease Fowler et al. BMC Cancer (2020) 20:2 Page 9 of 15 – – Female – – – – – – – – 60 70 80 90 – – – – – – – – 2 3 4 Most deprived – Obesity – – 2.39 – (1.69, 3.37) 1.89 – (1.34, 2.67) 1.48 – (1.03, 2.11) 1.19 – (0.83, 1.72) 1.00 5.17 – (4.13, 6.47) 5.74 – (4.49, 7.33) 5.03 – (4.04, 6.27) 3.36 – (2.89, 3.91) 1.00 0.62 – (0.50, 0.77) 1.00 Diabetes – – – – – – – – – – – – Dementia – – – – – – – – – – – – Hemi- or paraplegia – – – – – – – – – – – – CVD – – – – Renal disease 1.96 (1.55, 2.48) 1.48 (1.18, 1.87) 1.43 (1.14, 1.81) 1.26 (1.00, 1.60) 1.00 – – – – – 18.13 – (6.70, 49.03) 13.86 – (5.84, 32.91) 8.78 – (4.57, 16.86) 4.46 (3.00, 6.63) 1.00 0.88 (0.76, 1.02) 1.00 Hypertension – – – – – – – – – – – – MI – CHF – – 1.86 – (1.45, 2.38) 1.37 – (1.07, 1.77) 1.18 – (0.91, 1.54) 1.17 – (0.90, 1.52) 1.00 1.43 – (1.23, 1.66) 2.62 – (2.02, 3.39) 2.48 – (1.94, 3.18) 1.68 – (1.41, 2.00) 1.00 1.05 – (0.90, 1.23) 1.00 COPD – – – – – – – – – – – – PVD – – – – – – – – – – – – Rheum. conditions Abbreviations - CI confidence intervals, CVD Cerebrovascular disease, MI Myocardial infarction, COPD Chronic obstructive pulmonary disease, CHF Congestive heart failure, PVD Pheripheral vascular disease, REF reference, Rheum. Rheumatological – – Least deprived [REF] Deprivation group – – 45 [REF] Age at cancer diagnosis (years) – – Hodgkin lymphoma Male [REF] Sex Previous malignancy OR (95% CIs) Liver disease Table 2 Odds ratios of condition being present, by cancer (adjusted for other listed variables) (Continued) Fowler et al. BMC Cancer (2020) 20:2 Page 10 of 15