A small organ with a vital function

Abstract

Prostate cancer is a growing health-care problem in North America and Europe. The increasing frequency of this disease is caused in part by progress made in the treatment of cardiovascular disease, which has led to a rise in the number of elderly people. The prostate is a small organ with a very vital function, although it is only active for a short cumulative period during a man’s lifetime. The prostate gland produces the components that sperm need to survive between ejaculation and conception. There are several interesting facts about prostate cancer. Even though the prostate makes up less than 0·1% of a person’s body weight, around 30% of all male cancer arises in this small organ. There are also substantial differences in frequency of this cancer between different populations worldwide; AfricanAmericans living in the USA have a 100-fold increased risk of developing prostate cancer compared with African-Americans living in Shanghai, China, for example. Furthermore, prostate cancer is extremely uncommon in men younger than age 50 years (incidence <0·1%), and more than 85% of all cancers are diagnosed after age 65 years. Researchers do not know what happens during the sixth and seventh decade of life that triggers this sharp increase in incidence. Even though prostate cancer is generally diagnosed in elderly men, the mortality of this disease is substantial. In Sweden, more people die from prostate cancer than from any other malignant disease. Although prostate cancer is common, its cause is mostly unknown, with one exception. All epidemiological studies show that men who have a close relative who has had prostate cancer have a 2–4-fold increased risk of developing the disease (figure). The greater the number of family members with prostate cancer, and the younger the age of onset of the disease in the family, the more likely a man is of having prostate cancer himself. Studies in twins are done to estimate the genetic component of a disease by comparing its incidence in monozygotic and dizygotic twins. In a meta-analysis of twin registries in the Nordic countries, the chance of inheriting a predisposition for prostate cancer was 0·40. This result does not suggest that 40% of all prostate cancers are inherited, but rather that 40% of the overall risk factors are genetic, and 60% are nongenetic. To the surprise of the investigators, prostate cancer had the highest heretability of all cancers studied, even higher than breast cancer and colorectal cancer. The evidence therefore indicates that genetic factors are of great importance in the development of prostate cancer. Hereditary diseases are not as rare as suggested by my lecturers in medical school, nor are they generally diagnosed in the first decades of life, as noted in my college text books. Finding the genes that cause hereditary prostate cancer has not been as straightforward as scientists had hoped it would be, based on their experiences with the identification of genes for breast cancer and colon cancer. Several research groups worldwide have done extensive work to identify these genetic factors. In 1996, scientists from USA and Sweden localised the first prostate cancer susceptibility gene (HPC1) to chromosome 1. Since then, several additional prostate cancer genes (HPCX, PCAB, PCAP, HPC20, and ELAC2) have been located on different chromosomal loci. Despite extensive efforts, no gene for prostate cancer susceptibility has been fully identified and cloned. One explanation for this failure is that hereditary prostate cancer is a remarkably heterogeneous disease. Furthermore, the high rates of sporadic cases of the disease in families, its late age of onset, and the different modes of inheritance (dominant, recessive, and Xlinked), makes the identification of prostate cancer genes a very difficult task. Hopefully, the sequencing of the human genome will speed up identification of new prostate cancer susceptibility genes. As prostate cancer is one of the major diseases among men in the western world today, the need for a better understanding of the biology of the disease, to develop new therapies, is obvious. Identification of genes that are directly or indirectly involved in the development of prostate cancer will, no doubt, help to fight it. One preventive strategy involves the identification of high-risk populations, who can then be offered surveillance programmes. Once developed, preventive drugs could have an important role in these populations. Optimistically, such drugs could be available within the next 5–10 years. Family with hereditary prostate cancer Black square=prostate cancer; black and white squares and circles=cancer other than of the prostate; shape with the number 4 inside=four unaffected siblings; numbers outside shapes=age of onset of cancer.