Dataset Information

No association between FTO or HHEX and endometrial cancer risk.

ABSTRACT: INTRODUCTION:Obesity and diabetes are known risk factors for endometrial cancer; thus, the genetic risk factors of these phenotypes might also be associated with endometrial cancer risk. To evaluate this hypothesis, we genotyped tag-single nucleotide polymorphisms (SNP) and candidate SNPs in FTO and HHEX in a primary set of 417 endometrial cancer cases and 406 population-based controls, and validated significant findings in a replication set of approximately 2,347 cases and 3,140 controls from three additional studies. METHODS:We genotyped 189 tagSNPs in FTO (including rs8050136) and five tagSNPs in HHEX (including rs1111875) in the primary set and one SNP each in FTO (rs12927155) and HHEX (rs1111875) in the validation set. Per allele odds ratios (OR) and 95% confidence intervals (CI) were calculated to estimate the association between the genotypes of each SNPs (as an ordinal variable) and endometrial cancer risk using unconditional logistic regression models, controlling for age and site. RESULTS:In the primary study, the most significant finding in FTO was rs12927155 (OR, 1.56; 95% CI, 1.21-2.01; P = 5.8 x 10(-4)), and in HHEX, it was rs1111875 (OR, 0.80; 95% CI, 0.66-0.97; P = 0.026). In the validation studies, the pooled per allele OR, adjusted for age and study for FTO, was rs12927155 (OR, 0.94; 95% CI, 0.83-1.06; P = 0.29), whereas for HHEX, it was rs1111875 (OR, 1.00; 95% CI, 0.92-1.10; P = 0.96). CONCLUSION:Our data indicate that common genetic variants in two genes previously related to obesity (FTO) and diabetes (HHEX) by genome-wide association scans were not associated with endometrial cancer risk. IMPACT:Polymorphisms in FTO and HHEX are unlikely to have large effects on endometrial cancer risk but may have weaker effects.

SUBMITTER: Gaudet MM

PROVIDER: S-EPMC2919629 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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No association between FTO or HHEX and endometrial cancer risk.

Gaudet Mia M MM Yang Hannah P HP Bosquet Jesus Gonzalez JG Healey Catherine S CS Ahmed Shahana S Dunning Alison M AM Easton Doug F DF Spurdle Amanda B AB Ferguson Kaltin K O'Mara Tracy T Lambrechts Diether D Despierre Evelyn E Vergote Ignace I Amant Frederic F Lacey James V JV Lissowska Jola J Peplonska Beata B Brinton Louise A LA Chanock Stephen S Garcia-Closas Montserrat M

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20100720 8

<h4>Introduction</h4>Obesity and diabetes are known risk factors for endometrial cancer; thus, the genetic risk factors of these phenotypes might also be associated with endometrial cancer risk. To evaluate this hypothesis, we genotyped tag-single nucleotide polymorphisms (SNP) and candidate SNPs in FTO and HHEX in a primary set of 417 endometrial cancer cases and 406 population-based controls, and validated significant findings in a replication set of approximately 2,347 cases and 3,140 control ...[more]

PMID: 20647405

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Project description:A growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI).A total of 88 107 postmenopausal women aged 50-79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer.Over a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13-1.85 for diabetes, HR=1.57, 95% CI: 1.19-2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08-1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer risk.Our results suggest that the relationship observed in previous research between diabetes and endometrial cancer incidence may be largely confounded by body weight, although some modest independent elevated risk remains.

Project description:BACKGROUND:Murine double minute 2 homolog (MDM2) plays an important role in the downregulation of P53 tumor suppressor gene. MDM2 inhibits P53 transcriptional activity and thereby results in accelerated tumor formation. Overexpression of MDM2 has been found in several cancer types including endometrial cancer. SNP309 is located in the promoter region of MDM2 and contributes to the overexpression of MDM2. The association between MDM2 SNP309 polymorphism and endometrial cancer risk has been investigated in several studies; however, the conclusion remains controversial. OBJECTIVES:We performed the present meta-analysis to give a comprehensive conclusion of the association between MDM2 SNP309 polymorphism and endometrial cancer susceptibility. METHODS:We conducted a literature research on PubMed, Embase, Cochrane Library, OVID, Web of Science, Wan Fang, CNKI, and CQVIP databases up to July 31, 2018. Newcastle-Ottawa scale was used to assess the quality of studies. We evaluated the strength of association by combining odds ratios (ORs) and 95% confidence intervals (CIs) in 5 different genetic models under a fixed-effect model or random-effect model. We further conducted subgroup analysis by ethnicity, source of control, histological type, clinical type, grade, and stage of tumor. Sensitivity analysis and publication bias were also performed. RESULTS:Nine eligible studies were finally included in our meta-analysis. We found MDM2 SNP309 polymorphism increased the risk of endometrial cancer under allele model (OR: 1.23, 95% CI: 1.06-1.41, P?=?.005), homozygote model (OR: 1.43, 95% CI: 1.13-1.81, P?=?.003) and recessive model (OR: 1.55, 95% CI: 1.17-2.04, P?=?.002). Subgroup analysis suggested a similar elevated risk in both Asians and Caucasians. We identified a strong association of enhanced susceptibility to endometrial cancer in endometrioid group (OR: 2.13, 95% CI: 1.28-3.54, P?=?.004) and Type I group (OR: 1.89, 95% CI: 1.25-2.86, P?=?.002) under dominant model. We identified no significant publication bias according to Egger's test. CONCLUSIONS:Our meta-analysis suggested that MDM2 SNP309 polymorphism increased the risk of endometrial cancer significantly, especially in endometrioid and Type I endometrial cancer, indicating MDM2 could serve as a potential diagnostic factor marker for endometrial cancer.

Project description:OBJECTIVE:To evaluate the risk of a second primary cancer after endometrial cancer according to histological subtype. METHODS:Using data from the 13 National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries we identified women diagnosed with a primary endometrial cancer between 1992 and 2014. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for second primary cancer risk (all anatomical sites combined and for individual anatomical sites) among patients with endometrial cancer compared with the general population, in the overall study population and according to histological subtype. RESULTS:Among 96 256 women diagnosed with endometrial cancer, 8.4% (n=8083) developed a second primary cancer. The risk of second primary cancer was higher among patients with endometrial cancer than in the general population (SIR=1.05, 95% CI 1.03 to 1.07). We observed significantly higher second primary cancer risk among women with high grade endometrioid (SIR=1.12, 95% CI 1.05 to 1.19), serous (SIR=1.24, 95% CI 1.11 to 1.38), carcinosarcoma (SIR=1.18, 95% CI 1.02 to 1.35), mixed epithelial (SIR=1.22, 95% CI 1.06 to 1.40), and sarcoma (SIR=1.28, 95% CI 1.12 to 1.45) compared with the general population, but not for women with low grade endometrioid (SIR=1.01, 95% CI 0.98 to 1.03) or clear cell (SIR=1.09, 95% CI 0.88 to 1.33) endometrial cancer. Women with low grade endometrioid endometrial cancer had significantly lower second primary cancer risks in the gum and other mouth (SIR=0.57, 95% CI 0.30 to 0.97), lung and bronchus (SIR=0.72, 95% CI 0.66 to 0.77), and lymphocytic leukemia (SIR=0.71, 95% CI 0.54 to 0.93) while women with high risk endometrial cancer histological subtypes experienced significantly higher second primary cancer risk at several anatomical sites. CONCLUSIONS:Risk of developing second primary cancersat all anatomic sites combined and at individual anatomical sites varied according to histological subtype. Clinicians should be aware that women with different histological subtypes carry different second primary cancer risks .

Dataset Information

No association between FTO or HHEX and endometrial cancer risk.

Publications

No association between FTO or HHEX and endometrial cancer risk.

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