Genetic Variants at Chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 Influence the Risk of Breast Cancer in Men

• DOI: 10.1371/journal.pgen.1002290
• Publication Date: 2011-09-16T04:24:41Z
• Authors: Nick Orr; Rosie Cooke; Michael Jones; Olivia Fletcher; Frank Dudbridge; Sarah Chilcott-Burns; Katarzyna Tomczyk; Peter Broderick; Richard Houlston; Alan Ashworth; Anthony Swerdlow
• Keywords: Adult; Adolescent; Breast Neoplasms; QH426-470; Breast Neoplasms, Male; Electron Transport Complex IV; 03 medical and health sciences; 0302 clinical medicine; Copper Transport Proteins; Genetics; Chromosomes, Human; Genetic Predisposition to Disease; Genetic Association Studies; Aged; Chromosomes, Human, Pair 10; Genetic Variation; 3. Good health; Electron Transport Chain Complex Proteins; Case-Control Studies; Chromosomes, Human, Pair 2; Chromosomes, Human, Pair 5; Chromosomes, Human, Pair 6; Female; Apoptosis Regulatory Proteins; Chromosomes, Human, Pair 16; Research Article

Male breast cancer accounts for approximately 1% of all breast cancer. To date, risk factors for male breast cancer are poorly defined, but certain risk factors and genetic features appear common to both male and female breast cancer. Genome-wide association studies (GWAS) have recently identified common single nucleotide polymorphisms (SNPs) that influence female breast cancer risk; 12 of these have been independently replicated. To examine if these variants contribute to male breast cancer risk, we genotyped 433 male breast cancer cases and 1,569 controls. Five SNPs showed a statistically significant association with male breast cancer: rs13387042 (2q35) (odds ratio (OR) = 1.30, p = 7.98×10⁻⁴), rs10941679 (5p12) (OR = 1.26, p = 0.007), rs9383938 (6q25.1) (OR = 1.39, p = 0.004), rs2981579 (FGFR2) (OR = 1.18, p = 0.03), and rs3803662 (TOX3) (OR = 1.48, p = 4.04×10⁻⁶). Comparing the ORs for male breast cancer with the published ORs for female breast cancer, three SNPs--rs13387042 (2q35), rs3803662 (TOX3), and rs6504950 (COX11)--showed significant differences in ORs (p<0.05) between sexes. Breast cancer is a heterogeneous disease; the relative risks associated with loci identified to date show subtype and, based on these data, gender specificity. Additional studies of well-defined patient subgroups could provide further insight into the biological basis of breast cancer development.