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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: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.

Project description:To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status.Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors.UK Biobank.119,669 men and women of British ancestry, aged between 37 and 73 years.Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index.In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6 × 10(-3)) lower annual household income in men and a £1890 (£1680 to £2100; P=6 × 10(-15)) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6 × 10(-7)), and a £1130 (£680 to £1580) higher annual household income (P=4 × 10(-8)). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m(2)) caused a £2940 (£1680 to £4200; P=1 × 10(-5)) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only.These data support evidence that height and BMI play an important partial role in determining several aspects of a person's socioeconomic status, especially women's BMI for income and deprivation and men's height for education, income, and job class. These findings have important social and health implications, supporting evidence that overweight people, especially women, are at a disadvantage and that taller people, especially men, are at an advantage.

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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