Integrin alpha-2 and beta-3 gene polymorphisms and colorectal cancer risk.

Background And Aims: Integrins such as alpha(2)beta(1), alpha(IIb)beta(3), and alpha(v)beta(3) have been suggested as key players for cancer development and progression. Several polymorphisms affecting these molecules, two in integrin alpha(2) (ITGA2 807C>T and 1648G>A) and one in beta(3) (ITGB3 176T>C), influence their levels, structure, and possibly their function. To analyze the role of ITGA2 and ITGB3 polymorphisms for colorectal cancer risk and clinical presentation, we performed a case-control study.

A multigenic approach to predict breast cancer risk.

In the biology of complex disorders, such as breast cancer, interactions among genetic factors may play an important role and theoretical considerations suggest that gene-gene interactions are quite common in such diseases. In this case-control study with 500 breast cancer patients and 500 population-based healthy sex- and age-matched control subjects, we applied a multigenic approach to examine the associations with breast cancer risk of a comprehensive panel of 16 selected polymorphisms in a variety of pathways using classification tree analysis (CART). Overall, 79.

The cyclooxygenase-2 (PTGS2) 8473T>C polymorphism is associated with breast cancer risk.

Cyclooxygenase-2 (COX-2) is involved in carcinogenesis, immune response suppression, apoptosis inhibition, angiogenesis, and tumor cell invasion and metastasis. The gene for COX-2, designated as PTGS2, carries a common polymorphism at position 8473 in the 3'-untranslated region (PTGS2 8473T>C), which has been associated with susceptibility to malignant disease. To investigate the role of this polymorphism for breast cancer, we determined the prevalence of PTGS2 genotypes in 500 women with breast cancer and 500 sex- and age-matched healthy control subjects.

Genetic variants of the sulfotransferase 1A1 and breast cancer risk.

Sulfotransferase 1A1 (SULT1A1), also designated as phenol-preferring sulfotransferase, is involved in the bioactivation and detoxification of a variety of potential carcinogens, including iodothyronines, hydroxylated aromatic amines, and phenolic xenobiotics. A common arginine (R) to histidine (H) polymorphism at amino acid position 213 influences SULT1A1 activity and has been suggested as risk factor for a different types of cancers. To investigate the role of this polymorphism for breast cancer risk, SULT1A1 genotype was determined in 500 women with clinically verified breast cancer and 500 female age-matched healthy control subjects.

The 870G>A polymorphism of the cyclin D1 gene is not associated with breast cancer.

A common 870G > A polymorphism in the gene for cyclin D1, CCND1, has been linked to alternative splicing and cancer susceptibility. To analyze its role for breast cancer, we determined the CCND1 genotype in 500 breast cancer patients and 500 controls. CCND1 genotype frequencies were similar among patients and controls.

The common 677C>T gene polymorphism of methylenetetrahydrofolate reductase gene is not associated with breast cancer risk.

Methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism and plays a role in DNA biosynthesis, methylation, and repair in actively dividing cells. A common 677C>T polymorphism in the gene for MTHFR, leading to a thermolabile enzyme with decreased activity, has been associated with reduced plasma folate levels and elevated homocysteine levels and could be a risk factor for breast cancer. In the present case-control study, MTHFR genotype was determined in 500 women with clinically verified breast cancer and 500 female age-matched healthy control subjects.