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Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.

ABSTRACT: BACKGROUND: Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT). METHODS: We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case-control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model. RESULTS: One SNP (rs851987 in ESR1) tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007) and rs13281615 (on 8q24) tended to confer risk only in non users of HRT (p-for interaction = 0.03). There were no significant interactions after correction for multiple testing. CONCLUSIONS: We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.

SUBMITTER: Harlid S

PROVIDER: S-EPMC3460750 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.

Harlid Sophia S Butt Salma S Ivarsson Malin I L MI Eyfjörd Jorunn Erla JE Lenner Per P Manjer Jonas J Dillner Joakim J Carlson Joyce J

BMC women's health 20120622

<h4>Background</h4>Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT).<h4>Methods</h4>We analyzed samples from three different study populations: ...[more]

PMID: 22726230

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Project description:BackgroundChildren with familial dysautonomia (FD) are smaller and grow more slowly than the general population. It is unknown whether this abnormal growth is due to comorbidities that patients with FD live with, or if it is a direct effect of the disease-causing homozygous ELP-1 mutations. Here, we created growth curves for weight, height, and body mass index (BMI) in male and female children with FD to monitor the nutritional status of patients with FD.MethodsWe used the New York University (NYU) FD Registry which includes data from 680 individuals with FD who were followed longitudinally since birth. We generated sex-specific FD growth charts for three age ranges (birth to 36 months, 2 to 20 years, and 2 to 40 years) and compared them to the general population. We generated Kaplan-Meier curves to test the hypothesis that FD patients with low BMI had shorter survival than the rest of the cohort.ResultsGrowth charts generated from 591 individuals with FD show that these patients grow more slowly, reach less height, and gain less weight than the general population. The impact of FD on height was more pronounced in girls than in boys. However, both groups showed markedly low weights, which resulted in low BMI. Low weight, but not height, is already evident at birth. In a subpopulation of FD patients, we found that treatment with growth hormone or spinal fusion surgery helped patients achieve the expected growth characteristic of FD patients, but these treatments did not lead FD patients to achieve the growth pattern of the general population. Contrary to our hypothesis, low BMI had no impact on patient survival.ConclusionsPediatric patients with FD have lower height, weight, and BMI compared to the general pediatric population, but this does not appear to affect survival. Growth curves specific to the FD population are an important tool to monitor growth and nutritional status in pediatric patients with FD when the general population growth curves are of limited use.

Project description:BACKGROUND:Children with acute lymphoblastic leukemia (ALL) have an increased risk of obesity and short stature. To the authors' knowledge, data regarding patients treated on contemporary protocols without cranial irradiation are limited. METHODS:Changes in z scores for body mass index (BMI), height, and weight from the time of diagnosis to 5 years off therapy were evaluated using multivariable analysis in 372 children with ALL who were aged 2 to 18 years at the time of diagnosis and were enrolled on the St. Jude Children's Research Hospital Total XV protocol from 2000 through 2007. RESULTS:The percentage of overweight/obese patients increased from 25.5% at the time of diagnosis to approximately 50% during the off-therapy period. Median BMI z scores increased significantly during glucocorticoid therapy (induction: ?0.56; 95% confidence interval [95% CI], 0.29-0.64 [P<.001]; and reinduction II: ?0.22; 95% CI, 0.13-0.49 [P=.001]) and during the first year after therapy (?0.18; 95% CI, 0.08-0.46 [P=.006]). Among patients who were of healthy weight/underweight at the time of diagnosis, those aged 2 to <10 years at diagnosis had a significantly higher risk of becoming overweight/obese during or after therapy compared with those aged ?10 years (P=.001). Height z scores declined during treatment and improved after therapy. Being aged 2 to <10 years at the time of diagnosis, being of low-risk status, having a white blood cell count?<?50×109 /L at the time of diagnosis, and having negative central nervous system disease were associated with significantly better improvements in z scores for height during the off-therapy period compared with being aged ?10 years, being of standard-risk/high-risk status, having a white blood cell count ???50×109 /L, and having positive central nervous system disease, respectively. CONCLUSIONS:The results of the current study demonstrate that obesity is prevalent, and height growth, especially in patients with identified risk factors, appears compromised. Multidisciplinary intervention should begin during induction therapy and continue during the off-therapy period.

Dataset Information

Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.

Publications

Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.

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