Multiple pathway-based genetic variations associated with tobacco related multiple primary neoplasms.
PLoS One
; 7(1): e30013, 2012.
Article
en En
| MEDLINE
| ID: mdl-22253860
ABSTRACT
BACKGROUND:
In order to elucidate a combination of genetic alterations that drive tobacco carcinogenesis we have explored a unique model system and analytical method for an unbiased qualitative and quantitative assessment of gene-gene and gene-environment interactions. The objective of this case control study was to assess genetic predisposition in a biologically enriched clinical model system of tobacco related cancers (TRC), occurring as Multiple Primary Neoplasms (MPN).METHODS:
Genotyping of 21 candidate Single Nucleotide Polymorphisms (SNP) from major metabolic pathways was performed in a cohort of 151 MPN cases and 210 cancer-free controls. Statistical analysis using logistic regression and Multifactor Dimensionality Reduction (MDR) analysis was performed for studying higher order interactions among various SNPs and tobacco habit.RESULTS:
Increased risk association was observed for patients with at least one TRC in the upper aero digestive tract (UADT) for variations in SULT1A1 Arg²¹³His, mEH Tyr¹¹³His, hOGG1 Ser³²6Cys, XRCC1 Arg²8°His and BRCA2 Asn³7²His. Gene-environment interactions were assessed using MDR analysis. The overall best model by MDR was tobacco habit/p53(Arg/Arg)/XRCC1(Arg³99His)/mEH(Tyr¹¹³His) that had highest Cross Validation Consistency (8.3) and test accuracy (0.69). This model also showed significant association using logistic regression analysis.CONCLUSION:
This is the first Indian study on a multipathway based approach to study genetic susceptibility to cancer in tobacco associated MPN. This approach could assist in planning additional studies for comprehensive understanding of tobacco carcinogenesis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nicotiana
/
Variación Genética
/
Transducción de Señal
/
Predisposición Genética a la Enfermedad
/
Neoplasias Primarias Múltiples
Tipo de estudio:
Observational_studies
/
Qualitative_research
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2012
Tipo del documento:
Article
País de afiliación:
India