General theories (not time period specific)

A few theories have been thought of:

  • High levels of Insulin-like growth factor-1 (IGF-1) [Renehan, 2004; Tower RL & Spector LG, 2007]
  • First-born effect [Schuz, 1999; Greaves, 2001; Shu, 2002; Jourdan-Da Silva, 2004]
  • Miscarriages [Yeazel, 1995]
  • Birth Defects [Savitz & Ananth, 1994; Nishi, 2000]
  • Cancer in the family [Hemminki & Mutanen, 2001]
  • Autoimmune disorders in the family [McKinney, 1987; Buckley, 1989; Perillat-Menegaux, 2003]

High levels of Insulin-like growth factor-1 (IGF-1)

IGF-1 is a polypeptide protein hormone similar in molecular structure to insulin (that's why it is called insulin-like). It plays an important role in childhood growth. IGF-1 has been shown to stimulate the growth of both myeloid and lymphoid cells in laboratory cultures. Hence, it has been proposed that high levels of IGF-1 may both produce a larger baby (higher birth weight) and contribute to leukaemogenesis. Studies investigated the birth weight (high and low) with leukaemia, neuroblastoma, Wilm's tumour, lymphoma, osteosarcoma and hepatoblastoma but mixed results have been reported.

First-born effect

Some observations on animals suggest that there may be an environmental cause for the first-born effect. Along the west coast of Florida, nearly all the firstborn bottlenose dolphin calves die before they separate from their mothers. This is thought to be due to the high levels of environmental toxins in the fat of marine mammals. Research suggests mother dolphins unload as much as 80 percent of their accumulation of pollutants into each of their calves, probably through nursing. By theory, the firstborn gets the highest dose of pollutant as the mother has been accumulating toxins for many years while subsequent siblings receive the toxins accumulated over shorter periods.
Some studies showed an increased risk of leukaemia, generally for those under 5 years of age, associated with being the firstborn. There are also negative results studies.


Maternal history of previous miscarriages is a frequently reported risk factor for development of childhood ALL in a subsequent child except for infant leukaemia.

Birth Defects

An increased incidence of birth defects has been reported in childhood cancer, particularly in leukaemia.

Cancer in the family

Studies showed parental cancer as a risk factor to childhood cancer for nervous system cancers (CNS), lymphomas, endocrine tumours and retinoblastoma but no excess risk for leukaemia and Wilm's tumour.

Autoimmune disorders in the family

The risk association have been reported between autoimmune disorders in the family and leukaemia (ALL) and lymphoma.