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Supplementary materialsPersonal history of diabetes as important as family history of colorectal cancer for risk of colorectal cancer: A nationwide cohort studyAli Khan U, Fallah M, Tian Y, Sundquist K, Sundquist J, Brenner H, Kharazmi E eMethodsIn this study, we reported standard incidence ratios (SIRs), which could be considered comparable to hazards ratios (HRs) from Cox regression because previous studies have shown that both methods result in similar estimates that are also similar to risk ratios (RRs) calculated by Poisson regression or even negative binomial regression. For example, regardless of the method of calculation, familial risk of colorectal cancer (CRC) was around 1.9-fold in the Swedish family-cancer datasets [HR=1.9 ADDIN EN.CITE <EndNote><Cite><Author>Kharazmi</Author><Year>2012</Year><RecNum>2236</RecNum><DisplayText>(1)</DisplayText><record><rec-number>2236</rec-number><foreign-keys><key app="EN" db-id="ezdavffp3asesxe2sr759v9a0dxpt9zx99fr" timestamp="1583525742">2236</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kharazmi, E.</author><author>Fallah, M.</author><author>Sundquist, K.</author><author>Hemminki, K.</author></authors></contributors><auth-address>Division of Molecular Genetic Epidemiology, German Cancer Research Centre, 69120 Heidelberg, Germany. E.Kharazmi@dkfz.de</auth-address><titles><title>Familial risk of early and late onset cancer: nationwide prospective cohort study</title><secondary-title>Bmj</secondary-title><alt-title>BMJ (Clinical research ed.)</alt-title></titles><periodical><full-title>BMJ</full-title></periodical><pages>e8076</pages><volume>345</volume><edition>2012/12/22</edition><keywords><keyword>Age Factors</keyword><keyword>Age of Onset</keyword><keyword>Aged</keyword><keyword>Aged, 80 and over</keyword><keyword>Confidence Intervals</keyword><keyword>Female</keyword><keyword>*Genetic Predisposition to Disease</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Neoplasms/epidemiology/*genetics</keyword><keyword>Proportional Hazards Models</keyword><keyword>Prospective Studies</keyword><keyword>Risk Factors</keyword><keyword>Sweden/epidemiology</keyword></keywords><dates><year>2012</year><pub-dates><date>Dec 20</date></pub-dates></dates><isbn>0959-8138</isbn><accession-num>23257063</accession-num><urls></urls><custom2>PMC3527651</custom2><electronic-resource-num>10.1136/bmj.e8076</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>(1), SIR=1.9 PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5GcmFuazwvQXV0aG9yPjxZZWFyPjIwMTQ8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (2), average RR for an affected parent or an affected sibling=1.9 by both Poisson regression and negative binomial regression ADDIN EN.CITE <EndNote><Cite><Author>Frank</Author><Year>2015</Year><RecNum>1701</RecNum><DisplayText>(3)</DisplayText><record><rec-number>1701</rec-number><foreign-keys><key app="EN" db-id="sd0sfpsfraaevbe05tax9wtmvxd5apavsdvp" timestamp="1583152865">1701</key></foreign-keys><ref-type name="Thesis">32</ref-type><contributors><authors><author>Frank, Christoph</author></authors><tertiary-authors><author>Hemminki, K.</author></tertiary-authors></contributors><titles><title>Population landscape of familial cancer</title></titles><pages>59</pages><volume>Ph.D.</volume><number>1525377256</number><dates><year>2015</year></dates><publisher>Heidelberg University</publisher><work-type>Thesis</work-type><urls></urls></record></Cite></EndNote>(3)] and also in the Utah Population DataBase [HR=1.9 ADDIN EN.CITE <EndNote><Cite><Author>Samadder</Author><Year>2015</Year><RecNum>2238</RecNum><DisplayText>(4)</DisplayText><record><rec-number>2238</rec-number><foreign-keys><key app="EN" db-id="ezdavffp3asesxe2sr759v9a0dxpt9zx99fr" timestamp="1583526044">2238</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Samadder, N. Jewel</author><author>Smith, Ken Robert</author><author>Hanson, Heidi</author><author>Pimentel, Richard</author><author>Wong, Jathine</author><author>Boucher, Kenneth</author><author>Ahnen, Dennis</author><author>Singh, Harminder</author><author>Ulrich, Cornelia M.</author><author>Burt, Randall W.</author><author>Curtin, Karen</author></authors></contributors><titles><title>Increased Risk of Colorectal Cancer Among Family Members of All Ages, Regardless of Age of Index Case at Diagnosis</title><secondary-title>Clinical Gastroenterology and Hepatology</secondary-title></titles><periodical><full-title>Clinical Gastroenterology and Hepatology</full-title></periodical><pages>2305-2311.e2</pages><volume>13</volume><number>13</number><keywords><keyword>Colon Cancer</keyword><keyword>Inherited</keyword><keyword>Genetic Factor</keyword><keyword>Gender</keyword></keywords><dates><year>2015</year><pub-dates><date>2015/12/01/</date></pub-dates></dates><isbn>1542-3565</isbn><urls><related-urls><url>;(4);?SIR=1.9 ADDIN EN.CITE <EndNote><Cite><Author>Taylor</Author><Year>2010</Year><RecNum>2239</RecNum><DisplayText>(5)</DisplayText><record><rec-number>2239</rec-number><foreign-keys><key app="EN" db-id="ezdavffp3asesxe2sr759v9a0dxpt9zx99fr" timestamp="1583526106">2239</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Taylor, David P.</author><author>Burt, Randall W.</author><author>Williams, Marc S.</author><author>Haug, Peter J.</author><author>Cannon–Albright, Lisa A.</author></authors></contributors><titles><title>Population-Based Family History–Specific Risks for Colorectal Cancer: A Constellation Approach</title><secondary-title>Gastroenterology</secondary-title></titles><periodical><full-title>Gastroenterology</full-title><abbr-1>Gastroenterology</abbr-1></periodical><pages>877-885</pages><volume>138</volume><number>3</number><keywords><keyword>Colorectal</keyword><keyword>Relative Risk</keyword><keyword>UPDB</keyword></keywords><dates><year>2010</year><pub-dates><date>2010/03/01/</date></pub-dates></dates><isbn>0016-5085</isbn><urls><related-urls><url>;(5)].eResultsWe observed that the lifetime cumulative risk (age 0-79 years) for those with a diabetes mellitus (DM) diagnosis at any age was higher (7.2%, 95% CI: 7.2%-7.2%) than for those without a DM diagnosis (3.8%, 95% CI: 3.8%-3.8%) and for those with only one FDR with CRC (6.3%, 95% CI: 6.3%-6.4%; Table 2 in the main manuscript). The highest absolute risk was for those with a DM diagnosis at any age and at least two first-degree relatives (FDRs; 20%, 95% CI: 10.8%-28.3%). The lifetime CRC risk when one only had two or more FDRs with CRC and no DM diagnosis was 11% (95% CI: 9.9%-12.3%).eDiscussionA limitation of our study was lack of data on treatment of DM. However, our findings showed that patients with no family history of CRC who received a DM diagnosis in their 40s had a much higher risk of early-onset CRC diagnosed before age 50 (SIR=3.6, 95% CI: 2.8-4.5) than those with a DM diagnosis before age 30 (SIR=1.2, 95% CI: 0.8-1.6). Metformin is generally the first line of treatment for patients with DM type 2 ADDIN EN.CITE <EndNote><Cite><Author>Rojas</Author><Year>2013</Year><RecNum>1697</RecNum><DisplayText>(6)</DisplayText><record><rec-number>1697</rec-number><foreign-keys><key app="EN" db-id="sd0sfpsfraaevbe05tax9wtmvxd5apavsdvp" timestamp="1583150268">1697</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rojas, L. B.</author><author>Gomes, M. B.</author></authors></contributors><auth-address>Department of Medicine, Diabetes Unit, State University of Rio de Janeiro, Av 28 setembro 77, Rio de Janeiro CEP20555-030, Brazil. lilian_aguayo@.</auth-address><titles><title>Metformin: an old but still the best treatment for type 2 diabetes</title><secondary-title>Diabetol Metab Syndr</secondary-title></titles><periodical><full-title>Diabetology & Metabolic Syndrome</full-title><abbr-1>Diabetol. Metab. Syndr.</abbr-1><abbr-2>Diabetol Metab Syndr</abbr-2></periodical><pages>6</pages><volume>5</volume><number>1</number><edition>2013/02/19</edition><dates><year>2013</year><pub-dates><date>Feb 15</date></pub-dates></dates><isbn>1758-5996 (Print)
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ADDIN EN.CITE.DATA (7-9), we found elevated risk of CRC before age 50 in type 2 diabetic patients. Therefore, the true risk without metformin could have been even higher. Moreover, if insulin, which is the first line of treatment for type 1 DM and has association with increased risk of cancer ADDIN EN.CITE <EndNote><Cite><Author>Atkinson</Author><Year>2014</Year><RecNum>1699</RecNum><DisplayText>(10)</DisplayText><record><rec-number>1699</rec-number><foreign-keys><key app="EN" db-id="sd0sfpsfraaevbe05tax9wtmvxd5apavsdvp" timestamp="1583150701">1699</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Atkinson, M. A.</author><author>Eisenbarth, G. S.</author><author>Michels, A. W.</author></authors></contributors><auth-address>Department of Pathology and Department of Pediatrics, University of Florida, Gainesville, FL, USA. Electronic address: atkinson@ufl.edu.
Barbara Davis Center for Childhood Diabetes, Aurora, CO, USA.</auth-address><titles><title>Type 1 diabetes</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1><abbr-2>Lancet</abbr-2></periodical><pages>69-82</pages><volume>383</volume><number>9911</number><edition>2013/07/31</edition><keywords><keyword>Diabetes Mellitus, Type 1/complications/diagnosis/epidemiology/*therapy</keyword><keyword>Humans</keyword><keyword>Hypoglycemic Agents/administration & dosage/therapeutic use</keyword><keyword>Insulin/administration & dosage/therapeutic use</keyword><keyword>Islets of Langerhans/pathology</keyword><keyword>Pancreas, Artificial</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan 4</date></pub-dates></dates><isbn>1474-547X (Electronic)
0140-6736 (Linking)</isbn><accession-num>23890997</accession-num><urls><related-urls><url>(13)60591-7</electronic-resource-num></record></Cite></EndNote>(10), was the mediator of the association we found between DM and CRC, we would expect higher CRC risk in type 1 and lower risk in type 2 DM (due to metformin), which was not the case based on our large cohort study. Information on insulin use or end-organ manifestations of DM was lacking in this study. However, in previous studies greater DM severity, established by hemoglobin A1C (HgbA1C) concentration, a measure of DM control, and administration of insulin therapy, has been associated with CRC risk. In a prospective cohort study, a 1.3-fold increase in CRC risk was reported with every 1% increase in HgbA1C concentrations PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LaGF3PC9BdXRob3I+PFllYXI+MjAwNDwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (14) and aspirin is recommended to diabetic patients at high risk of coronary heart disease ADDIN EN.CITE <EndNote><Cite><Author>Armstrong</Author><Year>2010</Year><RecNum>1708</RecNum><DisplayText>(15)</DisplayText><record><rec-number>1708</rec-number><foreign-keys><key app="EN" db-id="sd0sfpsfraaevbe05tax9wtmvxd5apavsdvp" timestamp="1583510308">1708</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Armstrong, C.</author></authors></contributors><titles><title>Updated Recommendations on Daily Aspirin Use in Patients with Diabetes</title><secondary-title>American Family Physician</secondary-title><alt-title>Am Fam Physician</alt-title></titles><periodical><full-title>American Family Physician</full-title><abbr-1>Am. Fam. Physician</abbr-1><abbr-2>Am Fam Physician</abbr-2></periodical><alt-periodical><full-title>American Family Physician</full-title><abbr-1>Am. Fam. Physician</abbr-1><abbr-2>Am Fam Physician</abbr-2></alt-periodical><pages>1559-+</pages><volume>82</volume><number>12</number><dates><year>2010</year><pub-dates><date>Dec 15</date></pub-dates></dates><isbn>0002-838x</isbn><accession-num>WOS:000208405600013</accession-num><urls><related-urls><url><Go to ISI>://WOS:000208405600013</url></related-urls></urls><language>English</language></record></Cite></EndNote>(15). Aspirin is also associated with reduced risk of CRC ADDIN EN.CITE <EndNote><Cite><Author>Rothwell</Author><Year>2010</Year><RecNum>1709</RecNum><DisplayText>(16)</DisplayText><record><rec-number>1709</rec-number><foreign-keys><key app="EN" db-id="sd0sfpsfraaevbe05tax9wtmvxd5apavsdvp" timestamp="1583510380">1709</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Rothwell, P. M.</author><author>Wilson, M.</author><author>Elwin, C. E.</author><author>Norrving, B.</author><author>Algra, A.</author><author>Warlow, C. P.</author><author>Meade, T. W.</author></authors></contributors><auth-address>Stroke Prevention Research Unit, Department of Clinical Neurology, University of Oxford, Oxford, UK. peter.rothwell@clneuro.ox.ac.uk</auth-address><titles><title>Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials</title><secondary-title>Lancet</secondary-title></titles><periodical><full-title>Lancet</full-title><abbr-1>Lancet</abbr-1><abbr-2>Lancet</abbr-2></periodical><pages>1741-50</pages><volume>376</volume><number>9754</number><edition>2010/10/26</edition><keywords><keyword>Aspirin/*administration & dosage/adverse effects</keyword><keyword>Cardiovascular Diseases/prevention & control</keyword><keyword>Colonic Neoplasms/prevention & control</keyword><keyword>Colorectal Neoplasms/epidemiology/mortality/*prevention & control</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Incidence</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>Thrombosis/prevention & control</keyword></keywords><dates><year>2010</year><pub-dates><date>Nov 20</date></pub-dates></dates><isbn>1474-547X (Electronic)
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ADDIN EN.CITE.DATA (18). Detection bias due to family history of CRC, regardless, does not affect the main finding of our study, which proposes DM personal history is a risk factor for early-onset CRC. In addition, the investigation into the association between DM and CRC (which is not in any CRC screening guideline) is fairly young in comparison to the established association between CRC and family history (which is already in CRC screening guidelines), making it unlikely that patients with DM being referred to colonoscopy more often than those with a family history. Moreover, there is no clear evidence that DM associates with colonoscopy. In fact, diabetic patients are known for being poor at adhering to their DM treatment regimen ADDIN EN.CITE <EndNote><Cite><Author>Kurtz</Author><Year>1990</Year><RecNum>1687</RecNum><DisplayText>(19)</DisplayText><record><rec-number>1687</rec-number><foreign-keys><key app="EN" db-id="sd0sfpsfraaevbe05tax9wtmvxd5apavsdvp" timestamp="1581593433">1687</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kurtz, S. M.</author></authors></contributors><titles><title>Adherence to diabetes regimens: empirical status and clinical applications</title><secondary-title>Diabetes Educ</secondary-title></titles><periodical><full-title>Diabetes Educator</full-title><abbr-1>Diabetes Educ.</abbr-1><abbr-2>Diabetes Educ</abbr-2></periodical><pages>50-9</pages><volume>16</volume><number>1</number><edition>1990/01/01</edition><keywords><keyword>Diabetes Mellitus/diet therapy/*psychology/rehabilitation</keyword><keyword>Education, Nursing, Continuing</keyword><keyword>Humans</keyword><keyword>Internal-External Control</keyword><keyword>*Patient Compliance</keyword><keyword>Patient Education as Topic</keyword><keyword>Professional-Patient Relations</keyword><keyword>Socioeconomic Factors</keyword></keywords><dates><year>1990</year><pub-dates><date>Jan-Feb</date></pub-dates></dates><isbn>0145-7217 (Print)
0145-7217 (Linking)</isbn><accession-num>2178896</accession-num><urls><related-urls><url>;(19). Studies have observed that self-care in diabetes management is not up to standard in approximately 45% of patients with type 2 DM ADDIN EN.CITE <EndNote><Cite><Author>Polonsky</Author><Year>2016</Year><RecNum>1688</RecNum><DisplayText>(20)</DisplayText><record><rec-number>1688</rec-number><foreign-keys><key app="EN" db-id="sd0sfpsfraaevbe05tax9wtmvxd5apavsdvp" timestamp="1581593507">1688</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Polonsky, W. H.</author><author>Henry, R. R.</author></authors></contributors><auth-address>Behavioral Diabetes Institute, San Diego; University of California, San Diego.
University of California, San Diego; Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA, USA.</auth-address><titles><title>Poor medication adherence in type 2 diabetes: recognizing the scope of the problem and its key contributors</title><secondary-title>Patient Prefer Adherence</secondary-title></titles><periodical><full-title>Patient Prefer Adherence</full-title></periodical><pages>1299-307</pages><volume>10</volume><edition>2016/08/16</edition><keywords><keyword>HbA1c</keyword><keyword>glycemic control</keyword><keyword>hypoglycemia</keyword><keyword>medication adherence</keyword><keyword>psychosocial</keyword><keyword>type 2 diabetes</keyword></keywords><dates><year>2016</year></dates><isbn>1177-889X (Print)
1177-889X (Linking)</isbn><accession-num>27524885</accession-num><urls><related-urls><url>;(20). This makes it unlikely that patients with type 2 DM would be motivated to be regular in CRC screening (let alone earlier screening than the general population) when they struggle to even adhere to treatment recommendations for their disease.We also identified families that likely had patients with hereditary nonpolyposis colorectal cancer (HNPCC) based on Amsterdam II criteria. Removal of these individuals did not alter CRC familial risk estimates PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UaWFuPC9BdXRob3I+PFllYXI+MjAxOTwvWWVhcj48UmVj
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ADDIN EN.CITE.DATA (18). Irrespective of this, the major findings of this study were involving sporadic CRC and familial cases with only one diagnosed FDR, making it highly unlikely that HNPCC cases affected the observed risk estimates since Amsterdam II criteria specifies that a person should have at least three relatives with CRC to qualify for HNPCC testing. We were also able to exclude patients with inflammatory bowel disease (IBD) in our sensitivity analysis and ensured that IBD as a CRC risk factor was not confounding the association observed between DM and CRC.We also did not have data on lifestyle factors such as diet or physical activity, but we adjusted our results for sex, age, calendar period, socioeconomic status, and residential area to reconcile to some extent the effect of lifestyle factors on the association between DM and CRC risk and also the advantageous access to healthcare in large cities. In addition, we had information on hospitalization for chronic obstructive pulmonary diseases (COPD, as a surrogate to heavy smoking), alcoholism, and obesity; after further adjustment for these factors, our risk estimates did not change substantially.One way to check whether the association between DM and CRC is due to increased access of diabetic patients to health care or not is to see if another chronic medical condition similar to DM like hypertension, which would not normally be associated with CRC but does associate with increased access to health care, has an association with increased CRC incidence (supporting a detection bias). We did not have data on hypertension, but a study involving several cohorts from Sweden and other Scandinavian countries showed a very weak or no association between hypertension and colon or anorectal cancer risk [in men (1.1-fold per 10 mm Hg increment in mid-blood pressure and in women (0.95 to1.03-fold)], suggesting that detection bias could not have a major role in our results PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdG9ja3M8L0F1dGhvcj48WWVhcj4yMDEyPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (21). If the detection bias was the cause of the DM association with CRC risk, one would also expect a similar strong association with hypertension in both sexes, especially in women who seem to be more health conscious than men ADDIN EN.CITE <EndNote><Cite><Author>Ek</Author><Year>2015</Year><RecNum>1700</RecNum><DisplayText>(22)</DisplayText><record><rec-number>1700</rec-number><foreign-keys><key app="EN" db-id="sd0sfpsfraaevbe05tax9wtmvxd5apavsdvp" timestamp="1583150776">1700</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ek, S.</author></authors></contributors><auth-address>Information Studies, Abo Akademi University, Turku, Finland& Information Studies, University of Oulu, Oulu, Finland sek@abo.fi.</auth-address><titles><title>Gender differences in health information behaviour: a Finnish population-based survey</title><secondary-title>Health Promot Int</secondary-title></titles><periodical><full-title>Health Promotion International</full-title><abbr-1>Health Promot. Int.</abbr-1><abbr-2>Health Promot Int</abbr-2></periodical><pages>736-45</pages><volume>30</volume><number>3</number><edition>2013/08/30</edition><keywords><keyword>Adolescent</keyword><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Aged</keyword><keyword>Consumer Health Information/*methods</keyword><keyword>Female</keyword><keyword>Finland</keyword><keyword>Global Health</keyword><keyword>*Health Behavior</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Motivation</keyword><keyword>Sex Factors</keyword><keyword>Young Adult</keyword><keyword>Northern Europe</keyword><keyword>consumer health information</keyword><keyword>health awareness</keyword><keyword>health information seeking</keyword></keywords><dates><year>2015</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1460-2245 (Electronic)
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Health Promot Int 2015;30:736-45.Supplementary Table S1: Risk of colorectal cancer (CRC) by type of diabetes mellitus (DM) in period 1997-2015Follow-up periodRelative with CRCDM personal history by age at DM diagnosis (years)DM Age at CRC diagnosis (years)All ages<50≥50ObsSIR95% CI?ObsSIR95% CI?ObsSIR95% CI1997-2015NoNoNo72,514Reference?4,190Reference?68,324Reference<50Type 1711.20.91.5141.00.61.7571.20.91.6?Type 2941.51.21.8?263.52.35.1681.20.91.51 FDRType 151.40.53.348.62.321.010.30.01.8???Type 2113.01.55.4?5185.94261.80.73.9CRC = Colorectal cancer; DM = Diabetes mellitus; Obs = Observed number of colorectal cancer cases in each risk group; SIR = Standardized incidence ratio; FDR = First-degree relative; Bold values indicate significant risks.Supplementary Table S2: Standardized incidence ratio (SIR) of colorectal cancer by personal history of diabetes mellitus (DM), family history of CRC, and age at diagnosis of DM by CRC subsiteCRC subsiteRelative with CRCDM personal history by age at DM diagnosis (years)Age at CRC diagnosis (years)All ages<50≥50ObsSIR95% CIObsSIR95% CIObsSIR95% CIProximal colonNoNo58,333Reference?4,735Reference?53,598Reference?<502831.51.31.7?581.91.42.4?2251.41.21.6?<30471.51.12.0?221.40.92.1?251.51.02.2?30-39631.31.01.7?151.81.02.9?481.30.91.7?40-491731.51.31.8?212.91.84.4?1521.41.21.71 FDRNo2,3071.71.61.7?2352.42.12.7?2,0721.61.51.7?<50262.71.83.9?78.23.317?192.11.33.4Distal colonNoNo35,852Reference?2,216Reference?33,636Reference?<502071.51.31.7?392.31.73.2?1681.41.21.6?<30251.20.81.8?81.20.52.3?171.20.72.0?30-39471.41.01.8?102.01.03.7?371.30.91.7?40-491351.61.41.9?214.42.76.7?1141.51.21.81 FDRNo1,6991.71.71.8?1642.82.43.3?1,5351.71.61.8?<50192.51.53.9?6114.125?131.91.03.2RectumNoNo50,072Reference?3,129Reference?46,943Reference?<502481.21.11.4?441.81.32.4?2041.21.01.3?<30301.00.71.4?80.80.41.6?221.10.71.7?30-39511.00.81.4?81.10.52.1?431.00.81.4?40-491671.41.21.6?283.82.55.4?1391.21.01.51 FDRNo2,0271.51.51.6?1902.31.92.6?1,8371.51.41.5?<50181.71.02.6?22.50.39.1?161.60.92.6CRC = Colorectal cancer; DM = Diabetes mellitus; Obs = Observed number of colorectal cancer cases in each risk group; SIR = Standardized incidence ratio; Distal colon = Descending colon and sigmoid colon; FDR = First-degree relative; Bold values indicate significant risks.Supplementary Table S3: Risk of colorectal cancer (CRC) by type of diabetes mellitus (DM) in those without any inflammatory bowel disease (IBD)IBD statusRelative with CRCDM personal history by age at DM diagnosis (years)Age at CRC diagnosis (years)All ages<50≥50ObsSIR95% CI?ObsSIR95% CI?ObsSIR95% CINoNoNo138,975Reference?9,512Reference?129,463Reference<507001.41.31.51281.91.62.25721.31.21.4<30931.21.01.5?351.20.81.6?581.31.01.630-391511.21.11.5301.51.02.21211.21.01.440-494561.51.41.7?633.42.64.4?3931.41.31.51 FDRNo5,7831.61.61.75692.52.32.75,2141.61.51.6??<50602.31.83.0?136.43.411?472.01.42.6IBD = Inflammatory bowel disease; CRC = Colorectal cancer; DM = Diabetes mellitus; Obs = Observed number of colorectal cancer cases in each risk group; SIR = Standardized incidence ratio; FDR = First-degree relative; Bold values indicate significant risks. ................
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