title: No breast cancer association for transforming growth factor-beta pathway colorectal cancer single nucleotide polymorphisms.
abstract: SMAD7 and GREM1 are signaling components on the transforming growth factor-beta pathway, which regulates normal mammary gland development and has been implicated in breast tumor invasion and metastasis. Three variants within SMAD7 and two variants in CRAC1 (a colorectal cancer-associated region on chromosome 15 in which GREM1 is located) have been associated with colorectal cancer risks [odds ratios (OR), 0.85-1.26; all P < 10(-7)]. We genotyped these five variants in a series of 1,267 bilateral breast cancer cases and 900 controls to determine whether they are associated with breast as well as colorectal cancer risk. None of these single nucleotide polymorphisms were associated with breast cancer risk in our study and the 95% confidence limits of our data, pooled with data from the Cancer Genetic Markers of Susceptibility study, exclude per allele ORs of <0.94 or >1.08. One or more of these variants may be associated with a very small OR for breast cancer, but our data suggest that the effects of these alleles are cancer site-specific.
authors.affiliation: Non-Communicable Disease Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom. lorna.gibson@lshtm.ac.uk
authors.forename: Lorna
authors.initials: L
authors.lastname: Gibson
authors.forename: Nichola
authors.initials: N
authors.lastname: Johnson
authors.forename: Agnes
authors.initials: A
authors.lastname: Fraser
authors.forename: Isabel
authors.initials: I
authors.lastname: dos Santos Silva
authors.forename: Richard
authors.initials: R
authors.lastname: Houlston
authors.forename: Julian
authors.initials: J
authors.lastname: Peto
authors.forename: Olivia
authors.initials: O
authors.lastname: Fletcher
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D015220:Calcium Channels / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008875:Middle Aged; D000071740:ORAI1 Protein; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051906:Smad7 Protein / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D015220:Calcium Channels; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta