eAppendix Child socioeconomic conditions (CHSEC) and oral cancer 1. Syntax: Model 1: Total effect TITLE "TOTAL EFFECT OF CHSEC"; PROC GENMOD DATA=OCMSM DESCENDING; CLASS CENTRE; MODEL CASE_I= OCCP_CH_C2 PAT_ALC/ DIST=BINOMIAL LINK=LOG; REPEATED SUBJECT= CENTRE / TYPE= cs corrw covb; RUN; Model 2: Conventional regression TITLE "ADJUSTED EFFECT";*USED POISSON BECAUSE THE MODEL WAS NOT CONVERGING FOR DIST=BINOMIAL; PROC GENMOD DATA=OCMSM DESCENDING; CLASS CENTRE; MODEL CASE_I= OCCP_CH_C2 PAT_ALC SMK_NSMK CHW_NCHW DRNK_NDRNK SELF_EDU_C2 OCCP_ADLT_C2 AGE_2 SEX / DIST=POISSON LINK=LOG; REPEATED SUBJECT= CENTRE / TYPE= cs corrw covb; RUN; Model 4: Estimating CDE using marginal structural model Estimating weight for child socioeconomic condition Stabilized weight for CHSEC TITLE "CALCULATING DENOMINATOR OF WEIGHT FOR CHSEC DEPENDENT ON PATERNAL ALCOHOL"; PROC LOGISTIC DATA=CNTRLDTA DESCENDING OUTEST=PARAMS1; MODEL OCCP_CH_C2= PAT_ALC ;STRATA CENTRE; OUTPUT OUT=OCMSM P=PHAT; RUN; PROC LOGISTIC DATA=OCMSM DESCENDING INEST=PARAMS1; MODEL OCCP_CH_C2= PAT_ALC ;STRATA CENTRE; OUTPUT OUT=OCMSM P=PHAT; RUN; TITLE "CALCULATING NUMERATOR OF WEIGHT FOR CHSEC DEPENDENT ON PATERNAL ALCOHOL"; PROC LOGISTIC DATA=CNTRLDTA DESCENDING OUTEST=PARAMS2; MODEL OCCP_CH_C2=; RUN; PROC LOGISTIC DATA=OCMSM DESCENDING INEST=PARAMS2; MODEL OCCP_CH_C2=; OUTPUT OUT=OCMSM P=PHAT1; RUN; 1 TITLE "CALCULATING STABILIZED WEIGHT FOR CHSEC"; DATA OCMSM; SET OCMSM; IF OCCP_CH_C2=1 THEN SW=PHAT1/PHAT; ELSE IF OCCP_CH_C2=0 THEN SW=(1-PHAT1)/(1-PHAT); RUN; Stabilized weight for smoking TITLE "CALCULATING DENOMINATOR OF WEIGHT FOR SMOKING"; PROC LOGISTIC DATA=CNTRLDTA DESCENDING OUTEST=PARAMS3; MODEL SMK_NSMK= OCCP_CH_C2 SELF_EDU_C2 OCCP_ADLT_C2 AGE_2 SEX PAT_ALC CHW_NCHW DRNK_NDRNK ;STRATA CENTRE; RUN; PROC LOGISTIC DATA=OCMSM DESCENDING INEST=PARAMS3; MODEL SMK_NSMK= OCCP_CH_C2 SELF_EDU_C2 OCCP_ADLT_C2 AGE_2 SEX PAT_ALC CHW_NCHW DRNK_NDRNK; OUTPUT OUT=OCMSM P=PHAT2;STRATA CENTRE; RUN; TITLE "CALCULATING NUMERATOR OF WEIGHT FOR SMOKING"; PROC LOGISTIC DATA=CNTRLDTA DESCENDING OUTEST=PARAMS4; MODEL SMK_NSMK=OCCP_CH_C2;STRATA CENTRE; RUN; PROC LOGISTIC DATA=OCMSM DESCENDING INEST=PARAMS4; MODEL SMK_NSMK=OCCP_CH_C2 ; OUTPUT OUT=OCMSM P=PHAT3;STRATA CENTRE; RUN; DATA OCMSM; SET OCMSM; IF SMK_NSMK=1 THEN SWS=PHAT3/PHAT2; ELSE IF SMK_NSMK=0 THEN SWS=(1-PHAT3)/(1-PHAT2); RUN; DATA OCMSM; SET OCMSM; SW_SWS=SW*SWS; RUN; CDE of CHSEC controlled for smoking TITLE "SMOKING CONTROLLED DIRECT EFFECT OF CHSEC-CLUSTER"; PROC GENMOD DATA=OCMSM DESCENDING; CLASS CENTRE;WEIGHT SW_SWS; MODEL CASE_I= OCCP_CH_C2 SMK_NSMK / DIST=BINOMIAL LINK=LOG; REPEATED SUBJECT= CENTRE / type=cs corrw covb; RUN; Stabilized weight for chewing quid/alcohol TITLE "CALCULATING DENOMINATOR OF WEIGHT FOR CHEWING"; PROC LOGISTIC DATA=CNTRLDTA DESCENDING OUTEST=PARAMS5; 2 MODEL CHW_NCHW=OCCP_CH_C2 SELF_EDU_C2 OCCP_ADLT_C2 AGE_2 SEX PAT_ALC SMK_NSMK DRNK_NDRNK;STRATA CENTRE; RUN; PROC LOGISTIC DATA=OCMSM DESCENDING INEST=PARAMS5; MODEL CHW_NCHW=OCCP_CH_C2 SELF_EDU_C2 OCCP_ADLT_C2 AGE_2 SEX PAT_ALC SMK_NSMK DRNK_NDRNK;STRATA CENTRE; OUTPUT OUT=OCMSM P=PHAT4; RUN; TITLE "CALCULATING NUMERATOR OF WEIGHT FOR CHEWING"; PROC LOGISTIC DATA=CNTRLDTA DESCENDING OUTEST=PARAMS6; MODEL CHW_NCHW=OCCP_CH_C2;STRATA CENTRE; RUN; PROC LOGISTIC DATA=OCMSM DESCENDING INEST=PARAMS6; MODEL CHW_NCHW=OCCP_CH_C2 ;STRATA CENTRE; OUTPUT OUT=OCMSM P=PHAT5; RUN; DATA OCMSM; SET OCMSM; IF CHW_NCHW=1 THEN SWC=PHAT5/PHAT4; ELSE IF CHW_NCHW=0 THEN SWC=(1-PHAT5)/(1-PHAT4); SW_SWC=SW*SWC; RUN; CDE of CHSEC controlled for chewing TITLE "CHEWING CONTROLLED DIRECT EFFECT OF CHSEC-CLUSTER"; PROC GENMOD DATA=OCMSM DESCENDING; CLASS CENTRE ;WEIGHT SW_SWC; MODEL CASE_I= OCCP_CH_C2 CHW_NCHW / DIST=BINOMIAL LINK=LOG; REPEATED SUBJECT= CENTRE / type=cs corrw covb; RUN; Stabilized weight for alcohol TITLE "CALCULATING DENOMINATOR OF WEIGHT FOR ALCOHOL"; PROC LOGISTIC DATA=CNTRLDTA DESCENDING OUTEST=PARAMS7; MODEL DRNK_NDRNK= OCCP_CH_C2 SELF_EDU_C2 OCCP_ADLT_C2 AGE_2 SEX PAT_ALC CHW_NCHW SMK_NSMK;STRATA CENTRE; RUN; PROC LOGISTIC DATA=OCMSM DESCENDING INEST=PARAMS7; MODEL DRNK_NDRNK= OCCP_CH_C2 SELF_EDU_C2 OCCP_ADLT_C2 AGE_2 SEX PAT_ALC CHW_NCHW SMK_NSMK;STRATA CENTRE; OUTPUT OUT=OCMSM P=PHAT6 ; RUN; TITLE "CALCULATING NUMERATOR OF WEIGHT FOR ALCOHOL"; PROC LOGISTIC DATA=CNTRLDTA DESCENDING OUTEST=PARAMS8; MODEL DRNK_NDRNK=OCCP_CH_C2;STRATA CENTRE; RUN; 3 PROC LOGISTIC DATA=OCMSM DESCENDING INEST=PARAMS8; MODEL DRNK_NDRNK=OCCP_CH_C2 ;STRATA CENTRE; OUTPUT OUT=OCMSM P=PHAT7; RUN; DATA OCMSM; SET OCMSM; IF DRNK_NDRNK=1 THEN SWA=PHAT7/PHAT6; ELSE IF DRNK_NDRNK=0 THEN SWA=(1-PHAT7)/(1-PHAT6); SW_SWA=SW*SWA; RUN; CDE of CHSEC controlled for alcohol TITLE "ALCOHOL CONTROLLED DIRECT EFFECT OF CHSEC-CLUSTER"; PROC GENMOD DATA=OCMSM DESCENDING; CLASS CENTRE; WEIGHT SW_SWA; MODEL CASE_I= OCCP_CH_C2 DRNK_NDRNK/ DIST=BINOMIAL LINK=LOG; REPEATED SUBJECT= CENTRE / type=cs corrw covb; RUN; CDE of CHSEC controlled for smoking, chewing and alcohol (Final model) Final tabilized weights DATA OCMSM; SET OCMSM; SWSCA=.; SWSCA=SW*SWS*SWC*SWA; RUN; TITLE "CONTROLLED DIRECT EFFECT OF CHSEC-CONTROLLED FOR SMOKING, CHEWING AND ALCOHOL"; PROC GENMOD DATA=OCMSM DESCENDING; CLASS CENTRE; WEIGHT SWSCA; MODEL CASE_I= OCCP_CH_C2 SMK_NSMK CHW_NCHW DRNK_NDRNK/ DIST=BINOMIAL LINK=LOG; REPEATED SUBJECT= CENTRE / type=cs corrw covb; RUN; Additive interaction on risk ratio scale: Interaction between CHSEC and smoking: TITLE "RERI CHSEC SMK ON RR SCALE"; PROC NLMIXED DATA=OCMSM; 4 *LOGISTIC REGRESSION MODEL; ODDS = EXP(B0 +B1*OCCP_CH_C2 + B2*SMK_NSMK + B3*OCCP_CH_C2*SMK_NSMK); PI = ODDS/(1+ODDS); MODEL CASE_I~BINARY(PI); ESTIMATE 'P00' EXP(B0)/(1+EXP(B0)); ESTIMATE 'P01' EXP(B0+B1)/(1+EXP(B0+B1)); ESTIMATE 'P10' EXP(B0+B2)/(1+EXP(B0+B2)); ESTIMATE 'P11' EXP(B0+B1+B2+B3)/(1+EXP(B0+B1+B2+B3)); ESTIMATE 'ICR= RERI USING RR = P11/P00 - P10/P00 - P01/P00 + 1' EXP(B0+B1+B2+B3)/(1+EXP(B0+B1+ B2+B3))/ (EXP(B0)/(1+EXP(B0))) - EXP(B0+B2)/(1+EXP(B0+B2))/ (EXP(B0)/(1+EXP(B0))) - EXP(B0+B1)/(1+EXP(B0+B1)) / (EXP(B0)/(1+EXP(B0))) + 1; REPLICATE SW_SWS; RUN; Interaction between CHSEC and chewing; TITLE "RERI CHSEC CHW ON RR SCALE"; PROC NLMIXED DATA=OCMSM; *LOGISTIC REGRESSION MODEL; ODDS = EXP(B0 +B1*OCCP_CH_C2 + B2*CHW_NCHW + B3*OCCP_CH_C2*CHW_NCHW); PI = ODDS/(1+ODDS); MODEL CASE_I~BINARY(PI); ESTIMATE 'P00' EXP(B0)/(1+EXP(B0)); ESTIMATE 'P01' EXP(B0+B1)/(1+EXP(B0+B1)); ESTIMATE 'P10' EXP(B0+B2)/(1+EXP(B0+B2)); ESTIMATE 'P11' EXP(B0+B1+B2+B3)/(1+EXP(B0+B1+B2+B3)); ESTIMATE 'ICR= RERI USING RR = P11/P00 - P10/P00 - P01/P00 + 1' EXP(B0+B1+B2+B3)/(1+EXP(B0+B1+ B2+B3))/ (EXP(B0)/(1+EXP(B0))) - EXP(B0+B2)/(1+EXP(B0+B2))/ (EXP(B0)/(1+EXP(B0))) - EXP(B0+B1)/(1+EXP(B0+B1)) / (EXP(B0)/(1+EXP(B0))) + 1; REPLICATE SW_SWC; RUN; Interaction between CHSEC and alcohol TITLE "RERI CHSEC ALC ON RR SCALE"; PROC NLMIXED DATA=OCMSM; *LOGISTIC REGRESSION MODEL; ODDS = EXP(B0 +B1*OCCP_CH_C2 + B2*DRNK_NDRNK + B3*OCCP_CH_C2*DRNK_NDRNK); PI = ODDS/(1+ODDS); MODEL CASE_I~BINARY(PI); ESTIMATE 'P00' EXP(B0)/(1+EXP(B0)); ESTIMATE 'P01' EXP(B0+B1)/(1+EXP(B0+B1)); ESTIMATE 'P10' EXP(B0+B2)/(1+EXP(B0+B2)); ESTIMATE 'P11' EXP(B0+B1+B2+B3)/(1+EXP(B0+B1+B2+B3)); ESTIMATE 'ICR= RERI USING RR = P11/P00 - P10/P00 - P01/P00 + 1' EXP(B0+B1+B2+B3)/(1+EXP(B0+B1+ B2+B3))/ (EXP(B0)/(1+EXP(B0))) - EXP(B0+B2)/(1+EXP(B0+B2))/ (EXP(B0)/(1+EXP(B0))) - EXP(B0+B1)/(1+EXP(B0+B1)) / (EXP(B0)/(1+EXP(B0))) + 1; REPLICATE SW_SWA; RUN; Multiplicative interaction on risk ratio scale 5 CHSEC and smoking; TITLE "INTERACTION B/W CHSEC*SMOKING"; PROC GENMOD DATA=OCMSM DESCENDING; CLASS CENTRE ;WEIGHT SW_SWS; MODEL CASE_I= OCCP_CH_C2 SMK_NSMK OCCP_CH_C2*SMK_NSMK / DIST=BINOMIAL LINK=LOG; REPEATED SUBJECT= CENTRE / type=cs corrw covb; RUN; CHSEC and chewing; TITLE " INTERACTION B/W CHSEC*CHEWING"; PROC GENMOD DATA=OCMSM DESCENDING; CLASS CENTRE ;WEIGHT SW_SWC; MODEL CASE_I= OCCP_CH_C2 CHW_NCHW OCCP_CH_C2*CHW_NCHW / DIST=BINOMIAL LINK=LOG; REPEATED SUBJECT= CENTRE / type=cs corrw covb; RUN; CHSEC and alcohol; TITLE " INTERACTION B/W CHSEC*ALCOHOL"; PROC GENMOD DATA=OCMSM DESCENDING; CLASS CENTRE ;WEIGHT SW_SWA; MODEL CASE_I= OCCP_CH_C2 DRNK_NDRNK OCCP_CH_C2*DRNK_NDRNK/ DIST=BINOMIAL LINK=LOG; REPEATED SUBJECT= CENTRE / type=cs corrw covb; RUN; 6 2. Tables eTable 1 Joint distribution of Child SEC (CHSEC) and Smoking among cases and controls Cases (n) 64 76 11 26 CHSEC1 SMOKING1 CHSEC1SMOKING0 CHSEC0SMOKING1 CHSEC0SMOKING0 Controls (n) 39 131 15 87 eTable 2 RERI between child SEC and smoking ‡ Estimate Parameter Parameter Estimates Standard DF t Value Error Pr > |t| Alpha Lower Upper b0 b1 b2 b3 -1.01 0.46 0.84 0.30 0.21 0.26 0.56 0.64 433 433 433 433 -4.76 1.78 1.50 0.47 <.0001 0.076 0.135 0.638 0.05 0.05 0.05 0.05 -1.42 -0.05 -0.26 -0.95 -0.59 0.97 1.94 1.55 p00 p01 p10 p11 0.27 0.37 0.46 0.64 0.04 0.03 0.13 0.06 433 433 433 433 6.44 10.71 3.55 10.81 <0.001 <0.001 <0.001 <0.001 0.05 0.05 0.05 0.05 0.19 0.30 0.20 0.53 0.349 0.433 0.712 0.760 RERI using RR = p11/p00 p10/p00 - p01/p00 + 1 0.32 0.56 433 0.58 0.561 0.05 -0.77 1.420 Z Pr> |Z| -6.40 3.97 7.52 0.60 <.0001 <.0001 <.0001 0.5480 ‡Beta estimates for CHSEC =b1, Smoking =b2 and CHSEC*Smoking =b3 eTable 3 Multiplicative interaction between child SEC and smoking Parameter Intercept Child SEC Smoking Child SEC*Smoking Estimate -1.3352 0.3211 0.5363 0.0319 Standard Error 0.2085 0.0809 0.0714 0.0531 7 95% CI -1.7439 0.1625 0.3965 -0.0722 -0.9264 0.4796 0.6762 0.1360 eTable 4 Joint distribution of CHSEC and Chewing quid/tobacco (CHEWING) among cases and controls Cases (n) 101 39 20 17 CHSEC1 CHEWING1 CHSEC1 CHEWING0 CHSEC0 CHEWING1 CHSEC0 CHEWING0 Controls (n) 50 120 13 89 eTable 5 RERI between Child SEC and Chewing ‡ Estimate Parameter Parameter Estimates Standard DF t Value Error 0.25 433 -5.82 0.31 433 1.02 0.44 433 3.93 0.51 433 0.19 Pr > |t| Alpha Lower Upper <.0001 0.307 <.0001 0.851 0.05 0.05 0.05 0.05 -1.94 -0.29 0.87 -0.91 -0.96 0.93 2.60 1.10 b0 b1 b2 b3 -1.45 0.32 1.73 0.10 p00 p01 p10 p11 0.19 0.24 0.57 0.67 0.04 0.03 0.09 0.04 433 433 433 433 4.97 7.07 6.41 17.03 <.001 <.001 <.001 <.001 0.05 0.05 0.05 0.05 0.12 0.18 0.40 0.59 0.27 0.31 0.75 0.74 RERI using RR = p11/p00 p10/p00 - p01/p00 + 1 0.23 0.56 433 0.4 0.687 0.05 -0.88 1.33 ‡ Beta estimates for CHSEC =b1, Chewing =b2 and CHSEC*Chewing =b3 eTable 6 Multiplicative interaction between child SEC and chewing Parameter Intercept Child SEC Chewing Child SEC*Chewing Estimate -1.6769 0.2938 1.1284 -0.1447 Standard Error 0.4652 0.3261 0.6989 0.6011 95% CI -2.5887 -0.3453 -0.2414 -1.3228 -0.7651 0.9330 2.4982 1.0334 eTable 7 Joint distribution of CHSEC and alcohol among cases and controls 8 Z Pr> |Z| -3.60 0.90 1.61 -0.24 0.0003 0.3676 0.1064 0.8098 CHSEC1ALCOHOL1 CHSEC1ALCOHOL0 CHSEC0ALCOHOL1 CHSEC0ALCOHOL0 Cases (n) 74 66 19 18 Controls (n) 43 127 14 88 eTable 8 RERI between Child SEC and Alcohol Parameter‡ Estimate Parameter Estimates Standard DF t Value Error 0.28 433 -6.32 0.32 433 3.99 0.55 433 3.68 0.61 433 -1.32 Pr > |t| Alpha Lower Upper <0.001 <0.001 <0.001 0.187 0.05 0.05 0.05 0.05 -2.34 0.65 0.94 -2.00 -1.23 1.91 3.08 0.39 b0 b1 b2 b3 -1.78 1.28 2.01 -0.81 p00 p01 p10 p11 0.14 0.38 0.56 0.67 0.04 0.04 0.12 0.05 433 433 433 433 4.14 10.63 4.83 13.32 <.001 <.001 <.001 <.001 0.05 0.05 0.05 0.05 0.08 0.31 0.33 0.57 0.21 0.45 0.78 0.77 RERI using RR = p11/p00 - p10/p00 p01/p00 + 1 -0.84 1.01 433 -0.83 0.668 0.05 -2.82 1.15 ‡ Beta estimates for CHSEC=b1, Alcohol=b2 and CHSEC*Alcohol=b3 eTable 9 Multiplicative interaction between child SEC and alcohol Parameter Intercept Child SEC Alcohol Child SEC*Alcohol Estimate -1.9427 0.9673 1.3365 -0.7733 Standard Error 0.3528 0.1747 0.3917 0.2662 9 95% CI -2.6342 0.6250 0.5687 -1.2950 -1.2513 1.3097 2.1043 -0.2515 Z Pr> |Z| -5.51 5.54 3.41 -2.90 <.0001 <.0001 0.0006 0.0037 eTable 10 Sensitivity analysis for unmeasured confounding considering three estimates of controlled direct effect (CDE) of early-life socioeconomic condition (SEC) on oral cancer Sensitivity analysis for unmeasured confounder that would invalidate CDE not mediated by smoking 𝜸1a P11b P21c P11-P21d RR1e Sensitivity analysis for unmeasured confounder that would invalidate CDE not mediated by chewing 𝜸2f P12g P22h P12-P22i RR2j Sensitivity analysis for unmeasured confounder that would invalidate CDE not mediated by drinking 𝜸3k P13l P23m P13-P23n RR3 o 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 0.50 0.51 0.52 0.53 0.55 0.62 0.77 0.90 0.27 0.28 0.30 0.31 0.39 0.53 0.68 0.83 0.02 0.03 0.03 0.04 0.05 0.10 0.20 0.29 0.02 0.03 0.04 0.05 0.11 0.20 0.30 0.40 0.48 0.48 0.49 0.49 0.50 0.52 0.57 0.61 0.25 0.25 0.26 0.26 0.28 0.33 0.38 0.43 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 4 4 4 4 4 4 4 4 4 4 - 0.19 0.20 0.21 0.22 0.24 0.31 0.46 0.60 0.75 0.90 - 0.02 0.03 0.04 0.04 0.06 0.10 0.21 0.30 0.40 0.50 - 0.17 0.17 0.17 0.18 0.18 0.21 0.25 0.30 0.35 0.40 - 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 1.5 - 2 2 2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 3 4 4 4 4 4 4 4 4 4 4 4 0.26 0.27 0.28 0.30 0.36 0.48 0.61 0.60 0.14 0.15 0.16 0.17 0.18 0.24 0.37 0.49 0.61 0.74 0.86 0.11 0.11 0.12 0.13 0.14 0.20 0.33 0.45 0.57 0.70 0.82 0.02 0.03 0.04 0.05 0.10 0.20 0.30 0.30 0.02 0.03 0.04 0.04 0.05 0.10 0.21 0.30 0.40 0.50 0.60 0.03 0.03 0.04 0.04 0.05 0.10 0.21 0.30 0.40 0.50 0.60 0.24 0.24 0.24 0.25 0.26 0.28 0.31 0.30 0.12 0.12 0.12 0.13 0.13 0.14 0.16 0.19 0.21 0.24 0.26 0.08 0.08 0.08 0.09 0.09 0.10 0.12 0.15 0.17 0.20 0.22 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 1.2 3 3 3 3 3 3 3 4 4 4 4 4 4 4 - 0.51 0.52 0.53 0.55 0.57 0.66 0.86 0.35 0.36 0.37 0.39 0.41 0.70 0.90 - 0.02 0.03 0.03 0.04 0.05 0.10 0.20 0.02 0.03 0.03 0.04 0.05 0.20 0.31 - Note: Bias formula for CDE given by VanderWeeleTJ48 was used by specifying sensitivity parameters 𝛾, P1 and P2 to calculate RR; a 𝛾1 = conditional increase in the risk for oral cancer when smoking is the mediator in model 4; b P11= prevalence in smokers; c P21= prevalence in non-smokers; d P11-P21= Calculated differences in the probability of U; e RR1 = direct effect of child SEC controlled for smoking; f 𝛾2 = conditional increase in the risk for oral cancer when chewing is the mediator in model 4; g P12= prevalence in chewers; h P22= prevalence in non-chewers; i P12-P22= Calculated differences in the probability of U ; j RR2 = direct effect of child SEC controlled for chewing; 10 0.49 0.49 0.50 0.51 0.52 0.56 0.66 0.33 0.33 0.34 0.35 0.36 0.50 0.59 - 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 1.9 - k 𝛾3 = conditional increase in the risk for oral cancer when drinking is the mediator in model 4; l P13= prevalence in drinkers; m P23 = prevalence in non-drinkers; n P13-P23= Calculated differences in the probability of U; o RR3 = direct effect of child SEC controlled for drinking; eTable 11 Naive and Misclassification-corrected mediation analysis in the absence of mediator exposure interaction (Specificity = (0.75, 0.80, 0.85, 0.90, 0.95), Sensitivity = (0.75, 0.80, 0.85, 0.90, 0.95)), 95%CI obtained from bootstrap, effects not adjusted for clustering. Estimates (95%CI) Naïve CDEc (M= Smoking)b 1.38 (1.02-1.86) CDEc (M=Alcohol)b 1.89 (1.30-2.75) CDEc (M=Chewing)b 1.21 (0.92-1.59) SP=SN=0.95a 1.35 (0.98-1.82) 1.86 (1.24-2.75) 1.20 (0.90-1.56) SP=SN=0.90 a 1.33 (0.97-1.84) 1.84 (1.27-2.70) 1.19 (0.90-1.52) SP=SN=0.85 a 1.32 (0.98-1.84) 1.83 (1.27-2.70) 1.19 (0.90-1.52) SP=SN=0.80 a 1.31 (0.95-1.87) 1.82 (1.26-2.70) 1.19 (0.87-1.51) SP=SN=0.75 a 1.29 (0.95-1.79) 1.82 (1.26-2.70) 1.17 (0.87-1.54) a SP indicates Specificity and SN indicates Sensitivity M indicates mediator c CDE indicates controlled direct effect b 11 3. Life grid The life grid method was developed by Blane (1996) and validated by Berney and Blane (1997). It is very useful in collecting life-course information by recalling where cross-referencing with personal life events or historical events act as triggers in temporal referencing. In the present study, there were 12 columns in the life grid chart, arranged from left to right in order: year, external events, age, life events, area of residence, occupation, income, diet, smoking, Smokeless tobacco, quid and alcohol use. Crossreferencing each of the aspects along the columns with the participant’s own life events (marriage, birth of a child, death of a family member) and major external events during their lifetime (for example political events, a natural disaster) were used as triggers to improve the accuracy in recall (Blane, 1996; Berney and Blane, 2003). Initially changes in residential areas, occupational, dietary and behavioural histories were recorded with a life-grid that was later utilised as a guide throughout the structured part of the interview to keep a track of the timeline. Below is an example of the life grid used in the study. 12 ವರ್ಷ ಬಾಹ್ಯ ಘಟನೆಗಳು ವಯಸ್ಸು ಜೀವನದ ಘಟನೆಗಳು ವಾಸ್ಸ್ಥಳ ಉದೆ್ಯೀಗ ಆದಾಯ Year 1930 1931 External events Age Life events Born Occupation Income 1940 1947 Indian independence 1950 1960 1962 1970 1980 1984 Married Drought Assasination of Indira Gandhi 1990 2000 2010 13 Residence ವರ್ಷ ಆಹಾರ ಧೂಮಪಾನ ತಂಬಾಕು Year 1930 Diet Smoking Smokeless tobaccoQuid 1940 1950 1960 1970 1980 1990 2000 2010 14 ಎಲೆ-ಅಡಿಕೆ ಮದ್ಯಪಾನ Alcohol