Breast cancer protection by genomic imprinting in close kin families

Abstract

Human inbreeding generally reduces breast cancer risk (BCR). When the parents are biologically related, their infants have a lower birth weight due to smaller body organs. The undersized breasts, because of fewer mammary stem cells, have a lower likelihood of malignant conversion. Fetal growth is regulated by genomically imprinted genes which are in conflict; they promote growth when derived from the father and suppress growth when derived from the mother. The kinship theory explicates that the intensity of conflict between these genes affects growth and therefore the size of the newborn. In descendants of closely related parents, this gene clash is less resulting in a smaller infant. In this review, we elucidate the different mechanisms by which human inbreeding affects BCR, and why this risk is dissimilar in different inbred populations.

Breast Cancer in the United Arab Emirates

“…Available data about consanguinity and decreasing the risk of BC are conflicting. [45][46][47][48] In Arab women, the decrease in BC risk by parental consanguinity could be a result of the decreased gene conflict that is enhanced by a larger number of firstcousin marriages of the father's brother's son type and the protective effect of homozygosis of some still unidentified BC gene(s). 45 In a population-based case-control study looking at consanguinity and BC risk in the UAE, parental consanguinity decreased the risk of BC in younger women (, 50 years).…”

“…[45][46][47][48] In Arab women, the decrease in BC risk by parental consanguinity could be a result of the decreased gene conflict that is enhanced by a larger number of firstcousin marriages of the father's brother's son type and the protective effect of homozygosis of some still unidentified BC gene(s). 45 In a population-based case-control study looking at consanguinity and BC risk in the UAE, parental consanguinity decreased the risk of BC in younger women (, 50 years). 49 In another study from the UAE using computer simulation, the mating of nonconsanguineous and consanguineous populations was tracked over 40 generations, and it was evident that the BRCA1/2 carrier rate decreased on average by 0.022% every 25 years in a highly consanguineous population (six times faster than in a nonconsanguineous population).…”

Genomic imprinting analyses identify maternal effects as a cause of phenotypic variability in type 1 diabetes and rheumatoid arthritis

“…It is nevertheless assumed that less than 1% of all genes in mammals are imprinted 20,22 , however, they have important functions in stem cells, neuronal differentiation, development, and growth 22,23 . In humans, imprinted genes are associated with diseases such as Prader-Willi syndrome 24 , Angelman syndrome 25 , and cancer 26,27 . They are also assumed to affect susceptibility to diabetes.…”