title: Genetic variants at chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 influence the risk of breast cancer in men.
abstract: 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.
authors.affiliation: The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, United Kingdom. nicholas.orr@icr.ac.uk
authors.forename: Nick
authors.initials: N
authors.lastname: Orr
authors.forename: Rosie
authors.initials: R
authors.lastname: Cooke
authors.forename: Michael
authors.initials: M
authors.lastname: Jones
authors.forename: Olivia
authors.initials: O
authors.lastname: Fletcher
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.forename: Sarah
authors.initials: S
authors.lastname: Chilcott-Burns
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Tomczyk
authors.forename: Peter
authors.initials: P
authors.lastname: Broderick
authors.forename: Richard
authors.initials: R
authors.lastname: Houlston
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
authors.forename: Anthony
authors.initials: A
authors.lastname: Swerdlow
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics*; D016022:Case-Control Studies; D002877:Chromosomes, Human / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D000079922:Copper Transport Proteins; D045222:Electron Transport Chain Complex Proteins; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006609:High Mobility Group Proteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011980:Receptors, Progesterone / Q000235:genetics; D012307:Risk Factors; D015534:Trans-Activators; D044465:White People; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C484188:COX11 protein, human; D000079922:Copper Transport Proteins; D045222:Electron Transport Chain Complex Proteins; D006609:High Mobility Group Proteins; D024101:Mitochondrial Proteins; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators; D003576:Electron Transport Complex IV