Perinatal factors, growth and development, and osteosarcoma risk

Abstract

Osteosarcoma incidence patterns suggest an aetiologic role for perinatal factors, and growth and development. Osteosarcoma patients (n ¼ 158) and controls with benign orthopaedic conditions (n ¼ 141) under age 40 were recruited from US orthopaedic surgery departments. Exposures were ascertained by interview, birth, and growth records. Age-and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. Current height and age-and sex-specific height percentiles were not associated with osteosarcoma risk. Male cases, however, appeared to have an earlier adolescent growth period, and earlier attainment of final height (OR ¼ 7.1; 95% CI ¼ 1.6 -50 for o19 vs 19 þ years), whereas earlier puberty appeared protective with ORs of 0.41 (95% CI 0.18 -0.89) and 0.68 (95% CI 0.31 -1.5) for developing facial and pubic hair, respectively. High birth weight was associated with an elevated osteosarcoma risk (OR ¼ 3.9; CI ¼ 1.7 -10 for 4000 g vs 3000 -3500 g), although there was no trend in risk with increasing weight. These data provide some evidence that osteosarcoma is related to size at birth and in early adolescence, while earlier puberty in male subjects may be protective.

Analysis of Genes Critical for Growth Regulation Identifies Insulin-like Growth Factor 2 Receptor Variations with Possible Functional Significance as Risk Factors for Osteosarcoma

“…Reasons for nonparticipation in the questionnaire component of the study included death, extreme illness following surgery or failure to return for follow-up care, and refusal. Cases (6.3%) and controls (20%) completed interviews but declined to participate in the blood component of the study (10).…”

“…Study subjects and controls were drawn from the Bone Disease and Injury Study of Osteosarcoma initiated in 1995 by the Harvard School of Dental Medicine and the National Cancer Institute as described previously (9,10 Institutional review boards at each of the medical centers approved the study protocol and informed consent was obtained from all study subjects. Approximately 14% of eligible subjects were not enrolled and a further 3% declined to participate in any of the study components (10). Of subjects who were enrolled in the study, 93.5% of cases and 98% of controls completed interviews.…”

Pathology from evolutionary conflict, with a theory of X chromosome versus autosome conflict over sexually antagonistic traits

“…An indirect link between imprinting and childhood cancer comes from the association between higher birth weight, accelerated fetal growth, and higher rates of most of the major childhood cancers (17)(18)(19)(20)(21). To the extent that perturbations to imprinting can lead to misregulated growth, this association between growth and cancer may also link misregulated imprinting to cancer.…”

Age-Period-Cohort Analysis of Primary Bone Cancer Incidence Rates in the United States (1976–2005)

“…Higher male than female incidence rates in puberty and the early age at which OS incidence first peaks, at ages 10 to 14 and 15 to 19 years for girls and boys respectively, may indicate the importance of accelerated growth and hormonal differences. Very early-in-life characteristics including high birth weight have also been implicated in the etiology of OS (12).…”