ABSTRACT
BACKGROUND: Several recent epidemiologic studies examined the association between breast cancer risk and an inherited, single-nucleotide polymorphism in the HER2 gene, codon 655 G to A, which leads to an amino acid substitution of Ile to Val. Results of previous studies have been mixed, with most studies showing no association but some suggesting an association in younger women or women with a family history of breast cancer. METHODS: We conducted an association study of HER2 codon 655 genotype and breast cancer within the Carolina Breast Cancer study, a population-based, case-control study of in situ and invasive breast cancer in African American and white women in North Carolina. A total of 2015 cases and 1808 controls were genotyped. RESULTS: We observed no overall association between HER2 genotype and breast cancer. However, a modest positive association (OR = 2.3, 95% CI 1.0-5.3) was observed for Val/Val + Ile/Val versus Ile/Ile genotypes in women age 45 or younger with a family history of breast cancer. Val/Val homozygotes were more common among cases with in situ versus invasive disease (P = 0.002). Breast tumors from women with Val/Val genotype were more likely to exhibit HER2 overexpression, but the results were not statistically significant (P = 0.17). CONCLUSIONS: The HER2 codon 655 polymorphism may be one of many low-penetrant genes that make a minor contribution to breast cancer, particularly in subgroups of women. Additional large studies, as well as data pooling, will be needed to estimate the contribution of such genes to breast cancer risk.
Subject(s)
Black People/genetics , Breast Neoplasms/genetics , Genes, erbB-2/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , White People/genetics , Adult , Aged , Breast Neoplasms/pathology , Case-Control Studies , Codon , Female , Genotype , Humans , Immunohistochemistry , Middle Aged , Neoplasm Invasiveness , Odds Ratio , Pedigree , Point Mutation , Polymerase Chain Reaction , Risk FactorsABSTRACT
We evaluated polymorphisms in methylenetetrahydrofolate reductase (MTHFR), folate intake and alcohol consumption in relation to risk of colon cancer in a population-based case-control study in North Carolina. The study included 555 cases (244 African Americans and 311 whites) and 875 controls (331 African Americans and 544 whites). Total folate intake of <400 versus > or =400 microg/day showed a weak positive association with colon cancer among both African Americans [adjusted odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.0-2.0] and whites (OR = 1.6, 95% CI = 1.2-2.2). No association was observed with use of alcohol. Compared with wild-type genotypes, there was no association between the low activity MTHFR codon 677 TT genotype and colon cancer, but the low activity codon 1298 CC genotype was inversely associated with colon cancer in whites (OR = 0.5, 95% CI = 0.3-0.9). Unlike previous studies, we did not observe a strong protective effect of the codon 677 TT low-activity genotype when folate intake was high. Instead, we observed an increased risk of colon cancer when folate intake was low for participants with wild- type genotypes. Adjusted ORs for the combined effects of codon 677 CC and codon 1298 AA genotypes and folate intake <400 microg/day were 1.9 (95% CI = 1.1-3.4) in African Americans and 2.5 (95% CI = 1.2-5.2) in whites. Our results suggest that variation at MTHFR codon 1298 (within the COOH-terminal region) may be more important for colon cancer than variation at codon 677 (NH(2)-terminal region), and in populations where folate intake is low, wild-type MTHFR activity may increase risk for colon cancer.
