Pathology - Research Publications

Permanent URI for this collection

Search Results

Now showing 1 - 3 of 3
  • Item
    No Preview Available
    Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
    Garcia-Closas, M ; Hall, P ; Nevanlinna, H ; Pooley, K ; Morrison, J ; Richesson, DA ; Bojesen, SE ; Nordestgaard, BG ; Axelsson, CK ; Arias, JI ; Milne, RL ; Ribas, G ; Gonzalez-Neira, A ; Benitez, J ; Zamora, P ; Brauch, H ; Justenhoven, C ; Hamann, U ; Ko, Y-D ; Bruening, T ; Haas, S ; Doerk, T ; Schuermann, P ; Hillemanns, P ; Bogdanova, N ; Bremer, M ; Karstens, JH ; Fagerholm, R ; Aaltonen, K ; Aittomaki, K ; Von Smitten, K ; Blomqvist, C ; Mannermaa, A ; Uusitupa, M ; Eskelinen, M ; Tengstrom, M ; Kosma, V-M ; Kataja, V ; Chenevix-Trench, G ; Spurdle, AB ; Beesley, J ; Chen, X ; Devilee, P ; Van Asperen, CJ ; Jacobi, CE ; Tollenaar, RAEM ; Huijts, PEA ; Klijn, JGM ; Chang-Claude, J ; Kropp, S ; Slanger, T ; Flesch-Janys, D ; Mutschelknauss, E ; Salazar, R ; Wang-Gohrke, S ; Couch, F ; Goode, EL ; Olson, JE ; Vachon, C ; Fredericksen, ZS ; Giles, GG ; Baglietto, L ; Severi, G ; Hopper, JL ; English, DR ; Southey, MC ; Haiman, CA ; Henderson, BE ; Kolonel, LN ; Le Marchand, L ; Stram, DO ; Hunter, DJ ; Hankinson, SE ; Cox, DG ; Tamimi, R ; Kraft, P ; Sherman, ME ; Chanock, SJ ; Lissowska, J ; Brinton, LA ; Peplonska, B ; Klijn, JGM ; Hooning, MJ ; Meijers-Heijboer, H ; Collee, JM ; Van den Ouweland, A ; Uitterlinden, AG ; Liu, J ; Lin, LY ; Yuqing, L ; Humphreys, K ; Czene, K ; Cox, A ; Balasubramanian, SP ; Cross, SS ; Reed, MWR ; Blows, F ; Driver, K ; Dunning, A ; Tyrer, J ; Ponder, BAJ ; Sangrajrang, S ; Brennan, P ; Mckay, J ; Odefrey, F ; Gabrieau, V ; Sigurdson, A ; Doody, M ; Struewing, JP ; Alexander, B ; Easton, DF ; Pharoah, PD ; Leal, SM (PUBLIC LIBRARY SCIENCE, 2008-04)
    A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
  • Item
    Thumbnail Image
    Risk factors for breast cancer in young women by oestrogen receptor and progesterone receptor status
    McCredie, MRE ; Dite, GS ; Southey, MC ; Venter, DJ ; Giles, GG ; Hopper, JL (NATURE PUBLISHING GROUP, 2003-11-03)
    We used data from 765 cases and 564 controls in the population-based Australian Breast Cancer Family Study to investigate whether, in women under the age of 40, the profile of risk factors differed between breast cancer subtypes defined by joint oestrogen and progesterone receptor status. As hypothesised, no significant differences were found.
  • Item
    No Preview Available
    The intronic G13964C variant in p53 is not a high-risk mutation in familial breast cancer in Australia
    Marsh, A ; Spurdle, AB ; Turner, BC ; Fereday, S ; Thorne, H ; Pupo, GM ; Mann, GJ ; Hopper, JL ; Sambrook, JF ; Chenevix-Trench, G (BIOMED CENTRAL LTD, 2001)
    BACKGROUND: Mutations in BRCA1 and BRCA2 account for approximately 50% of breast cancer families with more than four affected cases, whereas exonic mutations in p53, PTEN, CHK2 and ATM may account for a very small proportion. It was recently reported that an intronic variant of p53--G13964C--occurred in three out of 42 (7.1%) 'hereditary' breast cancer patients, but not in any of 171 'sporadic' breast cancer control individuals (P = 0.0003). If this relatively frequent occurrence of G13964C in familial breast cancer and absence in control individuals were confirmed, then this would suggest that the G13964C variant plays a role in breast cancer susceptibility. METHOD: We genotyped 71 familial breast cancer patients and 143 control individuals for the G13964C variant using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis. RESULTS: Three (4.2%; 95% confidence interval [CI] 0-8.9%) G13964C heterozygotes were identified. The variant was also identified in 5 out of 143 (3.5%; 95% CI 0.6-6.4%) control individuals without breast cancer or a family history of breast cancer, however, which is no different to the proportion found in familial cases (P = 0.9). CONCLUSION: The present study would have had 80% power to detect an odds ratio of 4.4, and we therefore conclude that the G13946C polymorphism is not a 'high-risk' mutation for familial breast cancer.