Differences in survival for patients with familial and sporadic cancer

Abstract Therapy-related acute myeloid leukemia (t-AML) is a rare but fatal complication of cytotoxic therapy. Whereas sporadic cancer results from interactions between complex exposures and low-penetrance alleles, t-AML results from an acute exposure to a limited number of potent genotoxins. Consequently, we hypothesized that the effect sizes of variants associated with t-AML would be greater than in sporadic cancer, and, therefore, that these variants could be detected even in a modest-sized cohort. To test this, we undertook an association study in 80 cases and 150 controls using Affymetrix Mapping 10K arrays. Even at nominal significance thresholds, we found a significant excess of associations over chance; for example, although 6 associations were expected at P less than .001, we found 15 (Penrich = .002). To replicate our findings, we genotyped the 10 most significantly associated single nucleotide polymorphisms (SNPs) in an independent t-AML cohort (n = 70) and obtained evidence of association with t-AML for 3 SNPs in the subset of patients with loss of chromosomes 5 or 7 or both, acquired abnormalities associated with prior exposure to alkylator chemotherapy. Thus, we conclude that the effect of genetic factors contributing to cancer risk is potentiated and more readily discernable in t-AML compared with sporadic cancer.

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Tissue microarrays for testing basal biomarkers in familial breast cancer cases

Sao Paulo Medical Journal ◽

10.1590/s1516-31802007000400007 ◽

2007 ◽

Vol 125 (4) ◽

pp. 226-230 ◽

Cited By ~ 2

Author(s):

Rozany Mucha Dufloth ◽

Irina Matos ◽

Fernando Schmitt ◽

Luiz Carlos Zeferino

Keyword(s):

Breast Cancer ◽

Tissue Microarray ◽

Familial Breast Cancer ◽

Case Series ◽

Breast Cancer Case ◽

Cancer Case ◽

Microarray Technology ◽

Sporadic Cancer ◽

Familial Tumors ◽

Cancer Phenotype

CONTEXT AND OBJECTIVE: The proteins p63, p-cadherin and CK5 are consistently expressed by the basal and myoepithelial cells of the breast, although their expression in sporadic and familial breast cancer cases has yet to be fully defined. The aim here was to study the basal immunopro-file of a breast cancer case series using tissue microarray technology. DESIGN AND SETTING: This was a cross-sectional study at Universidade Estadual de Campinas, Brazil, and the Institute of Pathology and Mo-lecular Immunology, Porto, Portugal. METHODS: Immunohistochemistry using the antibodies p63, CK5 and p-cadherin, and also estrogen receptor (ER) and Human Epidermal Receptor Growth Factor 2 (HER2), was per-formed on 168 samples from a breast cancer case series. The criteria for identifying women at high risk were based on those of the Breast Cancer Linkage Consortium. RESULTS: Familial tumors were more frequently positive for the p-cadherin (p = 0.0004), p63 (p < 0.0001) and CK5 (p < 0.0001) than was sporadic cancer. Moreover, familial tumors had coexpression of the basal biomarkers CK5+/ p63+, grouped two by two (OR = 34.34), while absence of coexpression (OR = 0.13) was associ-ated with the sporadic cancer phenotype. CONCLUSION: Familial breast cancer was found to be associated with basal biomarkers, using tissue microarray technology. Therefore, characterization of the familial breast cancer phenotype will improve the understanding of breast carcinogenesis.

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Microsatellite Instability and its Significance to Hereditary and Sporadic Cancer

Microsatellite Markers ◽

10.5772/65065 ◽

2016 ◽

Author(s):

Jeffery W. Bacher ◽

Linda Clipson ◽

Leta S. Steffen ◽

Richard B. Halberg

Keyword(s):

Microsatellite Instability ◽

Sporadic Cancer

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