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‣ Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

Olsen, C.M.; Nagle, C.M.; Whiteman, D.C.; Ness, R.; Pearce, C.L.; Pike, M.C.; Rossing, M.A.; Terry, K.L.; Wu, A.H.; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group; Risch, H.A.; Yu, H.; Doherty, J.A.; Chang-Claude, J.; Hein
Fonte: BioScientifica Publicador: BioScientifica
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
Relevância na Pesquisa
Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case–control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m2; 95% CI 1.18–1.30), invasive endometrioid (1.17; 1.11–1.23) and invasive mucinous (1.19; 1.06–1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94–1.02), but increased risks for low-grade serous invasive tumours (1.13...

‣ CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer.

Thompson, Deborah J.; O?Mara, Tracy A.; Glubb, Dylan M.; Painter, Jodie N.; Cheng, Timothy; Folkerd, Elizabeth; Doody, Deborah; Dennis, Joe; Webb, Penelope M.; Australian National Endometrial Cancer Study Group (ANECS); Gorman, Maggie; Martin, Lynn; Hodgs
Fonte: Bioscientifica Publicador: Bioscientifica
Tipo: Article; published version
Relevância na Pesquisa
This is the author accepted manuscript. The final version is available from Bioscientifica via http://dx.doi.org/10.1530/ERC-15-0386; Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol concentrations. We analysed 2,937 SNPs in 6,608 endometrial cancer cases and 37,925 controls and report the first genome wide significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8x10-11). SNP rs727479 was also among those most strongly associated with circulating estradiol concentrations in 2,767 post-menopausal controls (P=7.4x10- 8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11- 1.21) is compatible with that predicted by the observed effect on estradiol concentrations (1.09, CI=1.03-1.21), consistent with the hypothesis that endometrial cancer risk is driven by estradiol. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction.; Fine-mapping analysis was supported by NHMRC project grant [ID#1031333] to ABS...