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Genes of detoxification are important modulators of hereditary medullary thyroid carcinoma risk

Authors

Errata

This article is corrected by:

  1. Errata: Genes of detoxification are important modulators of hereditary medullary thyroid carcinoma risk Volume 79, Issue 5, 750, Article first published online: 3 October 2013

Correspondence: Laura Sterian, Ward, Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences, PO Box 6111, Campinas, SP-Brazil. Tel.: +55 19 3521 9081; Fax: +55 19 3521 9081; E-mail: ward@fcm.unicamp.br

Summary

Context

Different inherited profiles of genes involved in cellular mechanisms of activation and detoxification of carcinogenic products can provide specific protection or determine the risk for cancer. Low-penetrance polymorphic genes related to the biotransformation of environmental toxins have been associated with susceptibility to and the phenotype of, human tumours.

Objective

To investigate the role of germline inheritance of polymorphisms in CYP1A2*F, CYP1A1 m1, GSTP1, NAT2 and TP53 genes in hereditary medullary thyroid carcinoma (HMTC) patients.

Design

This study was developed in University of Campinas (Unicamp).

Patients

We studied 132 patients with HMTC, 88 first-degree relatives of HMTC patients and 575 control individuals.

Measurements

All patients with MTC and their relatives were sequenced for the RET gene and five genes were genotyped using TaqMan® system.

Results

We observed that the inheritance of CYP1A2*F (OR = 2·10; 95% CI = 1·11–3·97; P = 0·022), GSTP1 (OR = 4·41; 95% CI = 2·47–7·88; P < 0·001) and NAT2 (OR = 2·54; 95% CI = 1·16–5·58; P = 0·020) variants increased the risk for HMTC. In addition, multiple regression analysis showed that the inheritance of GSTP1 polymorphisms was associated with the diagnosis in older patients (B = 8·0229; 95% IC = ± 5·5735; P = 0·0054). Concerning the group of HTMC relatives, CYP1A2*F (OR = 2:40; 95% CI = 1·19–4·86; P = 0·015), CYP1A1 m1 (OR = 2·79; 95% CI = 1:04–7·51; P = 0·042), GSTP1 (OR = 2·86; 95% IC = 1·53–5·32; P < 0·001) and NAT2 (OR = 2·25; 95% IC = 1·20–4·22; P = 0·012) were associated with HMTC risk.

Conclusions

We have demonstrated that the inheritance of specific genes determining the individual response to environmental toxins may contribute to the risk and phenotypic variability that exists in patients with HMTC. Moreover, we identified a group at risk in relatives of HMTC patients.

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