RGD Reference Report - Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer. - Rat Genome Database

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Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.

Authors: Zhang, B  Sun, T  Xue, L  Han, X 
Citation: Zhang B, etal., Carcinogenesis. 2007 May;28(5):1067-73. Epub 2006 Dec 20.
RGD ID: 2290054
Pubmed: PMID:17183065   (View Abstract at PubMed)

The FAS-FASL system plays crucial role in counterattack of cancer cell against immune system. This study examined the effects of FAS (-1377G/A and -670A/G) and FASL (-844T/C and 7896G/C) polymorphisms on breast cancer risk and apoptosis of T lymphocytes. The effect on breast cancer risk was determined by case-control analysis of 840 patients and 840 controls. The effects on T-lymphocyte apoptosis were determined by activation-induced cell death (AICD) of T cells ex vivo and by analyzing apoptotic tumor-infiltrating lymphocytes (TILs) in breast cancer tissue. We found moderately increased risk associated with FAS -1377AG [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.59] and -1377AA (OR, 1.36; 95% CI, 1.01-1.82) genotypes compared with the -1377GG genotype and decreased risk associated with FASL -844CT (OR, 0.76; 95% CI, 0.62-0.94) and -844TT (OR, 0.66; 95% CI, 0.43-1.00) genotypes compared with the -844CC genotype. T lymphocytes with the FASL -844CC genotype had heightened FASL expression that is associated with increased AICD of the T cells stimulated by MCF-7 cells or phytohemagglutinin compared with the FASL -844TT genotype (10.38 +/- 4.09% and 24.29 +/- 1.50% versus 6.03 +/- 0.41% and 17.96 +/- 3.66%; P < 0.05 and 0.001). Breast cancer patients with the FASL -844CC genotype had higher apoptotic TILs in their cancer tissues than those with the FASL -844TT genotype (33.7 +/- 1.2% versus 19.1 +/- 2.0%; P = 0.007). These findings indicate that functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
breast cancer susceptibilityIAGP 2290054DNA:polymorphism:promoter:-1377G>ARGD 
breast cancer susceptibilityISOFAS (Homo sapiens)2290054; 2290054DNA:polymorphism:promoter:-1377G>ARGD 
Breast Neoplasms susceptibilityIAGP 2290054DNA:polymorphism:promoter:-844T>CRGD 
Breast Neoplasms susceptibilityISOFASLG (Homo sapiens)2290054; 2290054DNA:polymorphism:promoter:-844T>CRGD 

Objects Annotated

Genes (Rattus norvegicus)
Fas  (Fas cell surface death receptor)
Faslg  (Fas ligand)

Genes (Mus musculus)
Fas  (Fas cell surface death receptor)
Fasl  (Fas ligand)

Genes (Homo sapiens)
FAS  (Fas cell surface death receptor)
FASLG  (Fas ligand)


Additional Information