Intrauterine environments and breast cancer risk: meta-analysis and systematic review

INTRODUCTION: Various perinatal factors, including birth weight, birth order, maternal age, gestational age, twin status, and parental smoking, have been postulated to affect breast cancer risk in daughters by altering the hormonal environment of the developing fetal mammary glands. Despite ample biologic plausibility, epidemiologic studies to date have yielded conflicting results. We investigated the associations between perinatal factors and subsequent breast cancer risk through meta-analyses. METHODS: We reviewed breast cancer studies published from January 1966 to February 2007 that included data on birth weight, birth order, maternal age, gestational age, twin status, and maternal or paternal smoking. Meta-analyses using random effect models were employed to summarize the results. RESULTS: We found that heavier birth weights were associated with increased breast cancer risk, with studies involving five categories of birth weight identifying odds ratios (ORs) of 1.24 (95% confidence interval [CI] 1.04 to 1.48) for 4,000 g or more and 1.15 (95% CI 1.04 to 1.26) for 3,500 g to 3,999 g, relative to a birth weight of 2,500 to 2,599 g. These studies provided no support for a J-shaped relationship of birthweight to risk. Support for an association with birthweight was also derived from studies based on three birth weight categories (OR 1.15 [95% CI 1.01 to 1.31] for > or =4,000 g relative to or =3,000 g relative to <3,000 g). Women born to older mothers and twins were also at some increased risk, but the results were heterogeneous across studies and publication years. Birth order, prematurity, and maternal smoking were unrelated to breast cancer risk. CONCLUSION: Our findings provide some support for the hypothesis that in utero exposures reflective of higher endogenous hormone levels could affect risk for development of breast cancer in adulthood

Gender mix in twins and fetal growth, length of gestation and adult cancer risk

This study evaluated the effect of gender mix (the gender combinations of twin pairs) on fetal growth and length of gestation, and reviewed the literature on the long-term effects of this altered fetal milieu on cancer risk. In singletons, it is well established that females weigh less than males at all gestations, averaging 125–135 g less at full term. This gender difference is generally believed to be the result of the effect of androgens on fetal growth. The gender difference in fetal growth is greater before the third trimester and less towards term, with males growing not only more, but also earlier than females. Plurality is a known risk factor for reduced fetal growth and birthweight. Compared with singletons, the mean birthweight percentiles of twins fall substantially (by 10% or more) below the singleton 10th percentile by 28 weeks, below the singleton 50th percentile by 30 weeks, and below the singleton 90th percentile by 34 weeks. In unlike-gender twin pairs, it has been reported that the female prolongs gestation for her brother, resulting in a higher birthweight for the male twin than that of like-gender male twins. Other researchers have demonstrated that females in unlike-gender pairs had higher birthweights than females in like-gender pairs. Analyses from our consortium on 2491 twin pregnancies with known chorionicity showed longer gestations and faster rates of fetal growth in both males and females in unlike-gender pairs compared with like-gender male or female pairs, although these differences were not statistically significant. The post-natal effects for females growing in an androgenic-anabolic environment include increased sensation-seeking behaviour and aggression, lowered visual acuity, more masculine attitudes and masculinising effects of the auditory system and craniofacial growth. In contrast, there is no evidence to suggest that there might be a similar feminising effect on males from unlike-gender pairs. This hormonal exposure in utero may influence adult body size and susceptability to breast cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71549/1/j.1365-3016.2005.00616.x.pd

Appropriate Body Mass Index Cut-Offs to Determine Thinness, Overweight and Obesity in South Asian Children in The Netherlands

BACKGROUND: Asian populations have an increased risk of developing cardiometabolic disorders at a lower body mass index (BMI) than other ethnic groups. Therefore, lower adult BMI cut-offs to determine overweight and obesity are recommended to assess the associated health risks for Asian (23 and 27.5 kg/m(2) respectively) and Asian Indian (23, 25 kg/m(2)) populations. The objective of this study was to develop BMI cut-offs for thinness, overweight, and obesity for South Asian children in the Netherlands, and to compare the BMI cut-offs and distribution with an Asian Indian reference, the WHO Child Growth Reference, and universal BMI cut-offs. METHODS: A reference cohort of 546 Surinamese South Asian boys and 521 girls, born between 1974–1976 (during the pre-obesity era) with 3408 and 3267 BMI measurements respectively, was retrospectively analysed. BMI-for-age charts were created with the LMS method. BMI centile curves passing through the cut-off points of 15 (thinness), 23 (overweight), 25 and 27.5 kg/m(2) (obesity) at 18y were drawn as cut-off levels. RESULTS: The BMI of Surinamese South Asian children had a similar distribution to the Asian Indian reference, apart from a lower mean and less variation. The BMI distribution differed considerably from the WHO reference and universal BMI criteria. The calculated BMI cut-offs corresponding to a BMI of 15, 23, 25, and 27.5 kg/m(2) at 18y were at the 7.1, 81.1, 89.8, and 95.5 percentile respectively in boys, and at the 2.7, 79.5, 89.2, and 95.2 percentile in girls. CONCLUSIONS: This is the first study proposing BMI cut-offs for South Asian children based on measurements from a prosperous population unaffected by the obesity epidemic. We recommend the use of these cut-offs in South Asian children in the Netherlands as these better reflect the health risks associated with thinness, overweight and obesity, and therefore may prevent the development of cardiometabolic disorders