当前位置： SCI文献检索 > CARCINOGENESIS期刊下所有文献 > Nucleotide excision repair core gene polymorphisms and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck.

Nucleotide excision repair core gene polymorphisms and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck.

Abstract：

:The nucleotide excision repair (NER) pathway is central in response to damage induced by environmental carcinogens. Efficiency of this pathway, probably genetically determined, may modulate individual risk of developing squamous cell carcinoma of the head and neck (SCCHN) as well as second primary malignancy (SPM) after the index tumor. We hypothesized that common non-synonymous and regulatory single-nucleotide polymorphisms (SNPs) in the NER core genes individually, and more probably collectively, associated with the risk of SPM. We genotyped for seven selected SNPs in 1376 incident SCCHN patients who were prospectively recruited between 1995 and 2006 and followed for SPM development. We found that 110 patients (8%) developed SPM: 43 (39%) second SCCHN; 38 (35%) other tobacco-associated sites and 29 (26%) other non-tobacco-associated sites. The associations of these SNPs with SPM risk were assessed assuming a recessive genetic model. We did not find any significant associations of each or in combination of the seven SNPs with SPM risk in the recessive models. However, when we explored the combined effect based on an alternatively dominant genetic model, we found that the number of observed risk genotypes was associated with a significantly increased SPM risk in a dose-response manner (P = 0.005) and patients with five to seven risk genotypes had a significantly 2.4-fold increased SPM risk compared with patients with zero to two risk genotypes. These findings suggest that a profile of NER core gene polymorphisms might collectively contribute to risk of SPM not in a recessive model but in a dominant model among patients with an index primary SCCHN. These findings need to be validated in future studies with larger sample sizes and longer follow-up time.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Zafereo ME,Sturgis EM,Liu Z,Wang LE,Wei Q,Li G

doi

10.1093/carcin/bgp096

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

997-1002

issue

eissn

0143-3334

issn

1460-2180

pii

bgp096

journal_volume

pub_type

杂志文章

在线工具

Nucleotide excision repair core gene polymorphisms and risk of second primary malignancy in patients with index squamous cell carcinoma of the head and neck.