Birthweight, early environment, and genetics: a study of twins discordant for acute myocardial infarction

Hübinette, Anna; Cnattingius, Sven; Ekbom, Anders; Fairé, Ulf dé; Kramer, Michael S.; Lichtenstein, Paul

doi:10.1016/s0140-6736(00)05111-4

Cited by 77 publications

(57 citation statements)

References 26 publications

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“…9 However, recent data suggest that high birth weight and long gestational age among twins are risk factors for breast cancer but whether these would modify the comparisons to the singleton population remains to be established. [11][12][13] The studies in families with multiple twins showed no excess risks of cancer among twins. In one family with 3 twins and an excess of breast cancer, the risk is unlikely to be related to twinning.…”

Section: Discussionmentioning

confidence: 99%

Cancer risks in twins: Results from the Swedish family‐cancer database

Hemminki

2002

Intl Journal of Cancer

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Twin studies on cancer have addressed two general questions, one about the possible carcinogenic effects of twinning and the second about heritable effects of cancer. The first question is answered by comparing the occurrence of cancer in twins to that in singletons; the second is answered in probandwise analysis of monozygotic twins compared to dizygotic twins or siblings. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 62,574 0 -66-year-old twins to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all main cancer compared to cancer in singletons. In probandwise analysis, the SIR was calculated for the co-twin of an affected twin. The overall risk of cancer in same or opposite sex twins was at the level of the risk for singletons. Testicular cancer was increased among same sex twins and all twins to an SIR of 1.43. Melanoma was decreased in these groups of twins to an SIR of 0.84. Some other cancer sites were increased or decreased in some groups of twins, but none in all twins. The SIR of breast cancer was 1.01 and 1.04 in same and opposite sex twins, respectively. Probandwise analysis showed increased risks for Hodgkin's disease in males and breast cancer and childhood acute lymphoid leukemia among females. The data on this unselected population of twins suggest that twinning per se is not a risk factor of cancer. However, because twins are smaller than singletons at birth, some possible effects could be masked by such differences. In utero hormonal exposures may be related to the risk of testicular cancer. The protective effects in melanoma may be due to socioeconomic factors.

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Section: Discussionmentioning

confidence: 99%

Cancer risks in twins: Results from the Swedish family‐cancer database

Hemminki

2002

Intl Journal of Cancer

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“…Moreover, this together with two other studies using the same approach applied to blood pressure suggests that causes of variation in fetal growth between twin pairs are sufficient to exert programming effects and draws attention to the importance of the fetal supply line (9,10). However, more recent studies have not confirmed these initial findings (11)(12)(13).…”

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confidence: 83%

The Influence of Maternal BMI and Age in Twin Pregnancies on Insulin Resistance in the Offspring

et al. 2002

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OBJECTIVE -There is strong evidence that low birth weight is associated with glucose intolerance and diabetes in adults. We have carried out a twin study to distinguish among maternal influences, which affect both twins; fetoplacental influences, which are unique to each twin; and the genetic factors that may underlie this association. RESEARCH DESIGN AND METHODS-We identified a sample of 423 twin pairs (250 monozygotic and 173 dizygotic) from the East Flanders Prospective Twin Survey who were born between 1964 and 1982. Data collected in this study included the mother's body composition and weight gain during pregnancy, the twins' birth weights, and gestational age. The twins (aged 18 -34 years) attended a research center for measurement of height, weight, and waist-tohip ratio as well as fasting glucose, proinsulin, and insulin concentrations.RESULTS -Among twin pairs discordant for birth weight, we found little evidence that the lighter twin had abnormal glucose-insulin metabolism in adult life. However, both a low prepregnancy maternal BMI and older maternal age at delivery were associated with hyperinsulinemia and evidence of insulin resistance in the offspring. Fasting insulin increased by 1.3% (95% CI 0.1-2.6%) per unit fall in maternal BMI and by 1.1% (0.02-2.0%) per year increase in maternal age. These associations were independent of the twins' BMI and waist-to-hip ratio and their zygosity.CONCLUSIONS -These novel findings suggest that in twin pregnancies, maternal factors are more important than fetoplacental factors in determining glucose-insulin metabolism in the offspring. Diabetes Care 25:2191-2196, 2002T here is strong evidence that low birth weight is associated with insulin resistance, impaired glucose tolerance, and type 2 diabetes in adult life (1). Because the nutrients and oxygen that a fetus receives are major determinants of its growth rate and eventual size at term, these observations have led to the hypothesis that diabetes may result from fetal undernutrition arising from an imbalance between the supply of nutrients to the fetus and its nutrient requirements (2). It is suggested that this imbalance results in metabolic and endocrine adaptations that benefit the fetus in the short term but are detrimental in the longer term. Relatively little, however, is known about the processes that lead to fetal nutrient imbalance. The availability of nutrients to the fetus is determined by both maternal factors such as the mother's nutritional status, which include her nutritional reserves and dietary intake, and the fetoplacental factors that govern the nutrient transfer to the fetus. Recently, a number of studies have suggested that a low maternal weight or BMI is linked with insulin resistance and hyperglycemia in the offspring (3-5). However, factors originating in the fetus, such as a genetic predisposition to both low birth weight and glucose intolerance (6), or local intrauterine influences, such as uteroplacental blood flow and the size of the placenta and its transfer capabilities, could a...

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“…Similarly, the twin-pair design can also be used to investigate whether low birthweight is associated with increased risk of CHD. Such a study has been carried out in Sweden (Hubinette et al, 2001) where, in a case-control design of 132 same-sex twin pairs discordant for myocardial infarction and 118 individually matched control twin pairs, there was no within-pair association between birth characteristics and risk of myocardial infarction. Clearly, further research is required to improve understanding of the causal pathways and, therefore, investigation of these hypotheses using the much larger numbers of twins in GenomEUtwin should help to elucidate the associations between birth characteristics and subsequent risk of CHD.…”

Section: Addressing the Life Course Events Hypothesis In Twin Studiesmentioning

confidence: 99%