Hormonal carcinogenesis and socio-biological development factors in endometrial cancer: a clinical review.
OBJECTIVE
Endometrial cancer is one of the most common invasive gynecologic malignancies in developed countries and the eighth leading cause of cancer death in women; it typically arises in the sixth or seventh decade of life. The aim of this review was to evaluate possible roles of genetic and socio-biological factors in type I endometrial cancer, largely confined to pre- and perimenopausal women, with a history of estrogen exposure and/or endometrial hyperplasia.


METHODS
An extensive literature review, from 1990 to 2007 was performed on modifiable risk factors for type I endometrial cancer. Additionally, carcinogenesis mechanisms, biomarker and hormonal and biomolecular approaches to cancer detection, progression and monitoring and socio-biological factors were reviewed.


RESULTS
Several socio-biological and lifestyle characteristics, such as hormone replacement therapy, glycemic index, obesity, alcohol use, antipsychotic medication, melatonin, physical activity and variants in hormone metabolism genes have been identified as risk factors for developing endometrial cancer of type I, the majority of which are associated with excess estrogens causing continued stimulation of the endometrium. There is a genetic link to non-polyposis colorectal cancer syndrome, but association of endometrial cancer risk to other genetic polymorphisms has yielded conflicting results.


CONCLUSIONS
Many factors linked to hormonal imbalance, such as obesity, weight change, body size, alcohol, hyper-androgenic states, glycemic index and antidepressant agents, influence the endometrial cancer risk, central to which are endogenous and exogenous estrogen hyperstimulation of the endometrium. Conversely, smoking cigarettes, diet, physical activity and melatonin production seem to reduce the risk of cancer development. Other external factors fit well with the unopposed estrogen theory, but more studies are needed to investigate modifiable and added risk factors for endometrial cancer.
Tinelli
Andrea
A
Department of Obstetrics and Gynaecology, Vito Fazzi Hospital, Lecce, Italy. andreatinelli@gmail.com
Vergara
Daniele
D
Martignago
Roberta
R
Leo
Giuseppe
G
Malvasi
Antonio
A
Tinelli
Raffaele
R
D000367:Age Factors; D014408:Biomarkers, Tumor / Q000378:metabolism; D004032:Diet; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D015444:Exercise / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D012307:Risk Factors
D014408:Biomarkers, Tumor