SUPPLEMENTARY MATERIALS AND METHODS Additionl informtion bout the twin cohorts Cncers in NorTwinCn re clssified ccording to the Interntionl Clssifiction of Diseses (ICD). Those dignosed in Denmrk before 1978 re clssified ccording to ICD-7 coding, nd the remining cncers dignosis codes hve been trnslted to the ICD-O prdigm. For this study, we defined colon cncers s ll mlignnt neoplsms of the lrge intestine, except the rectum (ICD-7: 153; ICD-O: C18). Proximl colon cncers were defined s those occurring in the cecum, ppendix, scending colon, heptic flexure, trnsverse colon or splenic flexure. Distl colon cncers included those dignosed in the descending or sigmoid colon. Colon cncers tht were dignosed in multiple or unspecified prts of the lrge intestine were not ctegorized into proximl or distl disese. Rectl cncers included neoplsms of the rectum nd rectosigmoid junction (ICD-7: 154; ICD-O: C199, C209), nd excluded cncers of the nus. Denmrk initited cncer registrtion in 1943. For these nlyses, Dnish twins were followedup through 2009, t which point 1,153 prticipnts hd been dignosed with colorectl cncer. Cncer registrtion in Finlnd strted in 1953, but zygosity in the Finnish Twin Cohort ws only determined beginning in 1974. We thus restricted nlyses to twin pirs live s of the ltter yer. 1 Through 2010, totl of 357 incident cses of colorectl cncer hd been dignosed in Finnish twins. Norwy estblished its registry of twin pirs in 1964. 2 As of 2008, 316 incident cses of colorectl cncer hd been dignosed in twins from Norwy. Lstly, for the Swedish cohort, we required tht twin pirs be live s of 1961 t the initition of their twin registry. 3,4 Between 1961 nd 2009, 1,268 twins from Sweden were dignosed with colorectl cncer.
In ll four countries zygosity ws determined by vlidted questionnire, which hs been shown to clssify more thn 95% of twin pirs correctly. 5 Twins identicl t the DNA sequence level were clssified s MZ nd those s geneticlly similr s full siblings were clssified s DZ.
REFERENCES 1. Kprio J, Koskenvuo M. Genetic nd environmentl fctors in complex diseses: the older Finnish Twin Cohort. Twin Res 2002;5:358-365. 2. Nilsen TS, Brndt I, Mgnus P, et l. The Norwegin Twin Registry. Twin Res Hum Genet 2012;15:775-780. 3. Lichtenstein P, De Fire U, Floderus B, et l. The Swedish Twin Registry: unique resource for clinicl, epidemiologicl nd genetic studies. J Intern Med 2002;252:184-205. 4. Pedersen NL, Lichtenstein P, Svedberg P. The Swedish Twin Registry in the third millennium. Twin Res 2002;5:427-432. 5. Christinsen L, Frederiksen H, Schousboe K, et l. Age- nd sex-differences in the vlidity of questionnire-bsed zygosity in twins. Twin Res 2003;6:275-278.
SUPPLEMENTARY TABLES Supplementry Tble S1. Number of pirs by vitl sttus for nlyses t the end of follow-up mong monozygotic (MZ) nd dizygotic (DZ) twin pirs in NorTwinCn Pirs (MZ / DZ) Dignosed w/ Cncer Decesed w/o Cncer Alive w/o Cncer Colorectl Cncer Mle Pirs Dignosed w/ Cncer 33 / 38 285 / 579 178 / 343 Decesed w/o Cncer 3,756 / 6,670 1,783 / 4,208 Alive w/o Cncer 12,834 / 18,600 Femle Pirs Dignosed w/ Cncer 40 / 32 243 / 558 237 / 361 Decesed w/o Cncer 3,724 / 6,508 1,787 / 3,689 Alive w/o Cncer 15,090 / 19,857 Colon Cncer Mle Pirs Dignosed w/ Cncer 10 / 16 161 / 327 110 / 195 Decesed w/o Cncer 3,885 / 6,902 1,829 / 4,330 Alive w/o Cncer 12,874 / 18,668 Femle Pirs Dignosed w/ Cncer 20 / 15 162 / 386 142 / 241 Decesed w/o Cncer 3,810 / 6,660 1,844 / 3,771 Alive w/o Cncer 15,143 / 19,932 Proximl Colon Cncer Dignosed w/ Cncer 11 / 9 136 / 308 120 / 185 Decesed w/o Cncer 7,881 / 13,948 3,757 / 8,270 Alive w/o Cncer 28,085 / 38,723 Distl Colon Cncer Dignosed w/ Cncer 5 / 3 131 / 267 111 / 207 Decesed w/o Cncer 7,891 / 13,978 3,757 / 8,286 Alive w/o Cncer 28,095 / 38,702 Rectl Cncer Mle Pirs Dignosed w/ Cncer 8 / 8 148 / 285 81 / 154 Decesed w/o Cncer 3,894 / 6,942 1,846 / 4,354 Alive w/o Cncer 12,892 / 18,695 Femle Pirs Dignosed w/ Cncer 6 / 5 106 / 197 103 / 131 Decesed w/o Cncer 3,875 / 6,857 1,868 / 3,846 Alive w/o Cncer 15,163 / 19,969 Note: Bold indictes number of pirs (MZ/DZ) tht re concordnt for sttus
Supplementry Tble S2. P-vlues for the equl thresholds ssumption in MZ nd DZ pirs with cumultive risks from ACE models llowing different risks in MZ nd DZ twins Cumultive Risk MZ (%) Cumultive Risk DZ (%) P-vlue Colorectl Cncer 4.6 4.5 0.03 Mle Pirs 4.8 4.5 0.002 Femle Pirs 4.5 4.3 0.18 Colon Cncer 2.8 2.7 0.10 Mle Pirs 2.6 2.5 0.17 Femle Pirs 2.8 2.8 0.80 Proximl 1.0 1.1 0.52 Distl 0.65 0.72 0.008 Rectl Cncer 1.8 1.7 <0.001 Mle Pirs 2.1 2.0 0.03 Femle Pirs 1.5 1.3 0.002
Supplementry Tble S3. Fmilil risk nd heritbility of cncers in NorTwinCn, specifying lterntive models to the ACE pproch for libility to disese, corrected for bis resulting from censoring nd competing risk of deth AE Model CE Model Fmilil Risk (%) Estimtes from Twin Modeling (%) Fmilil Risk (%) Estimtes from Twin Modeling (%) MZ DZ Heritbility Unique Envt. MZ DZ Common Envt. Unique Envt. Colorectl Cncer 18.1 (14.7, 22.1) 9.9 (8.7, 11.2) 40.2 (32.8, 47.5) 59.8 (52.5, 67.2) 13.1 (11.0, 15.5) 13.1 (11.0, 15.5) 29.0 (23.4, 34.5) 71.0 (65.5, 76.6) Mle Pirs 16.3 (11.7, 22.2) 9.4 (7.7, 11.4) 35.6 (24.5, 46.8) 64.4 (53.2, 75.5) 12.5 (9.6, 16.1) 12.5 (9.6, 16.1) 26.6 (18.3, 34.8) 73.4 (65.2, 81.7) Femle Pirs 20.3 (15.5, 26.1) 10.4 (8.8, 12.3) 45.0 (35.3, 54.7) 55.0 (45.3, 64.7) 13.8 (10.9, 17.3) 13.8 (10.9, 17.3) 31.5 (24.0, 38.9) 68.5 (61.1, 76.0) Colon Cncer 11.8 (8.6, 16.1) 6.1 (5.1, 7.4) 35.0 (25.6, 44.3) 65.0 (55.7, 74.4) 9.0 (6.9, 11.6) 9.0 (6.9, 11.6) 27.2 (20.1, 34.3) 72.8 (65.7, 79.9) Mle Pirs 8.9 (5.4, 14.3) 5.1 (3.8, 6.8) 27.8 (14.4, 41.1) 72.2 (58.9, 85.6) 7.7 (5.2, 11.3) 7.7 (5.2, 11.3) 23.9 (13.7, 34.1) 76.1 (65.9, 86.3) Femle Pirs 14.5 (9.5, 21.4) 7.1 (5.5, 9.1) 40.4 (27.7, 53.2) 59.6 (46.8, 72.3) 10.0 (7.0, 14.1) 10.0 (7.0, 14.1) 29.6 (19.8, 39.4) 70.4 (60.6, 80.2) Proximl 11.5 (6.9, 18.7) 4.1 (3.0, 5.7) 46.6 (33.8, 59.4) 53.4 (40.6, 66.2) 6.9 (4.4, 10.8) 6.9 (4.4, 10.8) 34.4 (24.3, 44.4) 65.6 (55.6, 75.7) Distl 6.6 (3.0, 14.0) 2.5 (1.5, 4.0) 37.9 (21.1, 54.6) 62.1 (45.4, 78.9) 3.7 (1.9, 7.3) 3.7 (1.9, 7.3) 26.4 (13.5, 39.3) 73.6 (60.7, 86.5) Rectl Cncer 7.0 (4.4, 11.1) 3.8 (2.8, 5.0) 27.6 (16.2, 38.9) 72.4 (61.1, 83.8) 5.4 (3.6, 7.9) 5.4 (3.6, 7.9) 21.5 (12.7, 30.3) 78.5 (69.7, 87.3) Mle Pirs 6.5 (3.4, 12.0) 3.9 (2.7, 5.6) 22.8 (7.7, 37.9) 77.2 (62.1, 92.3) 5.3 (3.1, 8.8) 5.3 (3.1, 8.8) 18.0 (6.3, 29.7) 82.0 (70.3, 93.7) Femle Pirs 7.8 (3.8, 15.4) 3.6 (2.3, 5.6) 33.2 (16.0, 50.4) 66.8 (49.9, 84.0) 5.5 (3.0, 9.9) 5.5 (3.0, 9.9) 25.4 (12.2, 38.6) 74.6 (61.4, 87.8)
Supplementry Tble S4. Akike Informtion Criterion (AIC) for ACE, ADE, AE, nd CE models ACE Model ADE Model AE Model CE Model Colorectl Cncer 145,825 145,825 145,823 145,892 Mle Pirs 73,684 Femle Pirs 71,754 73,686 73,692 71,752 71,811 Colon Cncer 100,815 100,824 100,822 100,820 Mle Pirs 46,827 Femle Pirs 53,571 46,840 46,825 53,569 53,589 Proximl 46,903 46,904 46,902 46,914 Distl 33,444 33,443 33,442 33,449 Rectl Cncer 72,194 72,197 72,195 72,195 Mle Pirs 39,623 Femle Pirs 30,853 ADE models were not estimble in nlyses strtified by sex; AIC estimtes re thus missing. 39,623 39,621 30,851 30,854