Role Of GSTM1 And GSTT1 Copy Number Variations In Differentiated Thyroid Cancer Risk In Europeans From Metropolitan France And Melanesians From New-Caledonia

Catherine Ines TCHEANDJIEU , Inserm U1018, France
EMILIE C. 1,2 , MARIE S. 1,2 , MULOT C. 3 , LAURENT-PUIG P. 3 , GUENEL P. 1,2 , TRUONG T. 1,2

1 CESP-Centre for research in Cancer Epidemiology and Population Health, Inserm U1018, Cancer Epidemiology: genes and environment, 94807 Villejuif, France
2 Univ Paris Sud 11, UMRS 1018, 94807 Villejuif, France
3 Université Paris Descartes, Inserm UMR 5775 EPIGENETEC, Paris, France

GSTM1 and GSTT1 are involved in the detoxification of various exogenous and endogenous substances. Copy number variations (CNVs) or deletion of these genes can lead to increase or decrease of enzyme activities. GSTM1 and GSTT1 deletions have been associated to risk of several cancers. We investigated whether CNVs of GSTM1 and GSTT1 influenced the risk of differentiated thyroid carcinoma (DTC) and whether they modify the association between DTC risk and previously described risk factors including body mass index (BMI), tobacco smoking, alcohol intake and reproductive factors such as age at menarche and numbers of pregnancy.
We analyzed GSTM1 and GSTT1 CNVs in 505 cases and 622 controls of European descent and, 156 cases and 114 controls of Melanesian descent from 2 population-based case-control studies conducted in Metropolitan France and in New Caledonia. 
GSTM1 and GSTT1 CNVs were not associated to DTC risk in Europeans and Melanesians. However, they modulated the association between DTC risk and BMI, alcohol drinking or tobacco smoking in both populations.
The OR contrasting BMI>25 to BMI≤25 kg/m² was stronger in GSTT1 non-carriers (OR(95%CI)= 2.87(1.14-7.22)) than in GSTT1 carriers (OR(95%CI)= 1.41(1.00-0.99)); the corresponding ORs in Melanesians women were 5.9(1.61-21.53) and 0.87(0.31-2.46), respectively. The strongest association of BMI with DTC was observed among Melanesians women deleted for GSTM1 and GSTT1 (OR(95%CI)=  9.36(2.09-41.84)).
In Europeans and Melanesians, we reported an inverse association between alcohol consumption and DTC risk that was stronger among subjects with deletion of GSTM1, GSTT1 and both GSTM1/GSTT1. Regarding cigarette smoking, we reported an inverse association with DTC risk among GSTM1/GSTT1 non-carriers, whereas a positive association was reported among carriers of at least 2 copies of GSTM1/GSTT1. No effect modification was observed for reproductive factors.
Our results suggest that GSTM1 and GSTT1 genotypes modify the association between DTC risk and BMI, cigarette smoking and alcohol drinking.