Melbourne School of Population and Global Health - Research Publications

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Author: English, Dallas × Author: Giles, Graham × Author: Hopper, John × End date: 2009 × Start date: 2006 ×

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    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.
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    Is there a positive association between mammographic density and bone mineral density?
    Dite, GS ; Wark, JD ; Giles, GG ; English, DR ; McCredie, MRE ; Hopper, JL (BMC, 2006)
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    A comparison of different methods for including 'age at menopause' in analyses of the association between hormone replacement therapy use and breast cancer
    Simpson, Julie A. ; English, Dallas R. ; MacInnis, Robert J. ; Gertig, Dorata M. ; Hopper, John L. ; Giles, Graham G. ( 2007)
    Background and methodology: Late ‘age at menopause’ is a recognised risk factor for postmenopausal breast cancer and is also associated with decreased use of hormone replacement therapy (HRT). When investigating the association between HRT use and breast cancer risk it is therefore necessary to adjust for the potential confounder, ‘age at menopause’. ‘Age at menopause’, however, cannot be determined for women with a hysterectomy and ovarian conservation. Using data on 13 357 postmenopausal women in whom 396 cases of invasive breast cancer were diagnosed during 9 years of follow-up from the Melbourne Collaborative Cohort Study, we compared the estimates of relative risk of HRT use for breast cancer for three different methods of dealing with missing data: complete-case analysis single imputation and multiple imputation. Results: ‘Age at menopause’ was missing for 17% of the data. Both HRT use and ‘age at menopause’ were significant risk factors for breast cancer, although ‘age at menopause’ only marginally confounded the estimates of risk for HRT. Women with ‘age at menopause’ missing did not represent a random sample of the population. Complete-case analyses resulted in higher estimates of the risk associated with HRT use compared with the different methods of imputation. Discussion and conclusions: We recommend that analyses investigating the association between HRT and breast cancer should present the results in two ways: excluding women with ‘age at menopause’ missing and including the women using multiple imputation. For both methods, estimates of risk, with and without the adjustment of ‘age at menopause’, should be given.