Other risk factors for pancreatic cancer: Hormonal aspects

Abstract

Exocrine pancreatic cancer is significantly more common in younger men than in younger women. The male-to-female sex ratio is, in most countries, between 1.25 and 1.75 to 1, but decreases with increasing age. Moreover, prior oophorectomy appeared in one study to be significantly more common in women with pancreatic cancer than in controls. This has raised interest in sex hormones in the development in pancreatic cancer. It has been questioned if there are estrogen receptors in ductal pancreatic cancer, but there are no doubt estrogen receptors and estrogen-binding protein in human healthy pancreas. It is also well proven that it is possible to influence experimental pancreatic cancer with estrogens. However, in clinical studies tamoxifen has repeatedly been shown to be without significant effects. On the other hand, there are also androgen receptors in pancreatic cancer and testosterone has been shown to strongly promote growth in experimental pancreatic cancers. It is therefore of considerable interest that an antiandrogen recently was shown to significantly prolong life in patients with unresectable pancreatic carcinoma. However, in patients with advanced pancreatic carcinoma the S-testosterone is low, far lower than what could be expected due to weight-loss and malnourishment alone. Pancreatic cancer has etiologically been connected to diet, for example the intake of fat. Cholecystokinin receptors have been found on human pancreatic cancer, possible to stimulate in vitro by cholecystokinin (CCK). Studies with CCK-receptor binding, hybridization with radiolabeled complementary DNA (cDNA) probes, or reverse-transcription polymerase chain reaction have shown that CCK-A receptors also are present in rat pancreatic putative preneoplastic lesions and cancer tissue, rat pancreatic-cancer cell lines, pancreatic carcinomas in transgenic mice, hamster pancreatic cancer, and human pancreatic cancer cell lines and tumors. Also, CCK-B receptors have been found in some human pancreatic cancers. There are a vast number of experiments done on CCK-stimulation of pancreatic cancer. They indicate that CCK may have a promotional effect on exocrine pancreatic cancer, but it is not probable that hyperstimulation with CCK alone induce pancreatic cancer. At present, however, despite a lot of evidence for a hormone-dependence of pancreatic cancer there are no data confirming a role for estrogens, androgens, CCK or their antagonists in clinical treatment of exocrine pancreatic cancer.