Clinical and genetic predictors of weight gain in patients diagnosed with breast cancer

Background: Post-diagnosis weight gain in breast cancer patients has been associated with increased cancer recurrence and mortality. Our study was designed to identify risk factors for this weight gain and create a predictive model to identify a high-risk population for targeted interventions. Methods: Chart review was conducted on 459 breast cancer patients from Northwestern Robert H. Lurie Cancer Centre to obtain weights and body mass indices (BMIs) over an 18-month period from diagnosis. We also recorded tumour characteristics, demographics, clinical factors, and treatment regimens. Blood samples were genotyped for 14 single-nucleotide polymorphisms (SNPs) in fat mass and obesity-associated protein (FTO) and adiponectin pathway genes (ADIPOQ and ADIPOR1). Results: In all, 56% of patients had >0.5 kg m–2 increase in BMI from diagnosis to 18 months, with average BMI and weight gain of 1.9 kg m–2 and 5.1 kg, respectively. Our best predictive model was a primarily SNP-based model incorporating all 14 FTO and adiponectin pathway SNPs studied, their epistatic interactions, and age and BMI at diagnosis, with area under receiver operating characteristic curve of 0.85 for 18-month weight gain. Conclusion: We created a powerful risk prediction model that can identify breast cancer patients at high risk for weight gain

Constitutively decreased TGFBR1 allelic expression is a common finding in colorectal cancer and is associated with three TGFBR1 SNPs

Purpose: Constitutively decreased TGFBR1 allelic expression is emerging as a potent modifier of colorectal cancer risk in mice and humans. This phenotype was first observed in mice, then in lymphoblastoid cell lines from patients with microsatellite stable colorectal tumors. Patients and Methods: We assessed the frequency of constitutively decreased TGFBR1 allelic expression and association with SNPs covering the TGFBR1 locus using RNA and DNA extracted from the peripheral blood lymphocytes of 118 consecutive patients with biopsy-proven adenocarcinoma of the colon or the rectum. Results: We found that 11(9.3%) of 118 patients exhibited decreased TGFBR1 allelic expression (TGFBR1 ASE). TGFBR1 ASE was strongly associated with three SNPs in linkage disequilibrium with each other: rs7034462 (p = 7.2 × 10-4), TGFBR1*6A (p = 1.6 × 10-4) and rs11568785 (p = 1.4 × 10-4). Conclusion: These results confirm the high prevalence of constitutively decreased TGFBR1 allelic expression among patients with colorectal cancer. The association of this phenotype with TGFBR1*6A, rs7034462 and rs1156875 suggests an association between TGFBR1 SNPs and colorectal cancer, which warrants additional studies

The role of the fat mass and obesity associated gene (FTO) in breast cancer risk

<p>Abstract</p> <p>Background</p> <p>Obesity has been shown to increase breast cancer risk. <it>FTO </it>is a novel gene which has been identified through genome wide association studies (GWAS) to be related to obesity. Our objective was to evaluate tissue expression of FTO in breast and the role of FTO SNPs in predicting breast cancer risk.</p> <p>Methods</p> <p>We performed a case-control study of 354 breast cancer cases and 364 controls. This study was conducted at Northwestern University. We examined the role of single nucleotide polymorphisms (SNPs) of intron 1 of <it>FTO </it>in breast cancer risk. We genotyped cases and controls for four SNPs: rs7206790, rs8047395, rs9939609 and rs1477196. We also evaluated tissue expression of FTO in normal and malignant breast tissue.</p> <p>Results</p> <p>We found that all SNPs were significantly associated with breast cancer risk with rs1477196 showing the strongest association. We showed that FTO is expressed both in normal and malignant breast tissue. We found that <it>FTO </it>genotypes provided powerful classifiers to predict breast cancer risk and a model with epistatic interactions further improved the prediction accuracy with a receiver operating characteristic (ROC) curves of 0.68.</p> <p>Conclusion</p> <p>In conclusion we have shown a significant expression of FTO in malignant and normal breast tissue and that <it>FTO </it>SNPs in intron 1 are significantly associated with breast cancer risk. Furthermore, these <it>FTO </it>SNPs are powerful classifiers in predicting breast cancer risk.</p

Role of polymorphisms in Adamantiades-Behçet&apos;s disease

Objective. We previously showed that Adamantiades-Behçet&apos;s disease (A-BD) is associated with a lower incidence of malignancy compared with the general population. Transforming growth factor-β (TGF-β) has been shown to play a role in cartilage regeneration and is increased in patients with A-BD. We also found 2 functional polymorphisms of the TGF-β pathway, TGFBR1*6A and TGFB1*CC, that are associated with risk of malignancy. We tested whether incidence of these polymorphisms would differ in patients with A-BD compared with healthy controls of similar age and geographic location. Methods. We performed a case-control study including 139 cases and 128 controls from Greece. Cases and controls were genotyped for TGFBR1*6A and TGFB1*CC. Results. We found that cases had lower incidence of TGFBR1*6A compared with controls (11.3% vs 13.3%, respectively). Also, the incidence of TGFB1*CC was lower in cases than controls (24.6% vs 27.0%, respectively). These differences were not statistically significant. Conclusion. Although there is a suggestion that the lower incidence of TGFBR1*6A in A-BD patients may play a protective role against development of malignancy, larger studies would be needed to fully evaluate the role of TGF-β and its polymorphisms in A-BD. Copyright © 2008. All rights reserved