Renal cell carcinoma is the most common form of kidney cancer. However, the genetic basis of renal cancer is not fully understood. Estrogens and their receptors (ERs) have been shown to play a role in various cancers and it is speculated that they can also affect the human kidney. One of the animal models utilized to study the effects of estrogens on renal cancer is the Syrian hamster. Exposing these hamsters to estrogens results in the development of kidney cancer and thus, the hormone-ER complex may be playing a role. The ER is expressed in reproductive as well as non-reproductive tissues and is implicated in the control of proliferation, differentiation, and development of many tissues. There are two types of ERs and they are the alpha and beta forms. Genetic polymorphisms of various factors have been shown to play a role in the alteration of their functions. The NH2-terminal region of the ERalpha protein influences its structure and function and thus, inherited variants of the ERalpha gene may alter tissue responsiveness to estrogens and possibly lead to renal carcinogenesis. Polymorphisms have been determined in the coding region of the human ERalpha gene and are located at the following codons: 10 T-->C, 85 G-->C, 87 G-->C, 243 C-->T, 325 C-->G, and 594 G-->A. There are also two polymorphisms that have been identified in intron 1 and give rise to a PvuII and XbaI restriction site. These polymorphisms of ERalpha have been shown to be associated with various cancers. Based on the evidence, it is hypothesized that polymorphisms of the ERalpha gene are associated with renal cell carcinoma.