Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 3–10% of cancer. Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer, and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), which is present in about 3% of people with colorectal cancer, among others. Statistically for cancers causing most mortality, the relative risk of developing colorectal cancer when a first-degree relative (parent, sibling or child) has been diagnosed with it is about 2. The corresponding relative risk is 1.5 for lung cancer, and 1.9 for prostate cancer. For breast cancer, the relative risk is 1.8 with a first-degree relative having developed it at 50 years of age or older, and 3.3 when the relative developed it when being younger than 50 years of age.Taller people have an increased risk of cancer because they have more cells than shorter people. Since height is genetically determined to a large extent, taller people have a heritable increase of cancer risk. Physical agents
Some substances cause cancer primarily through their physical, rather than chemical, effects. A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers that are a major cause of mesothelioma (cancer of the serous membrane) usually the serous membrane surrounding the lungs.
People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis and strict treatment, probably due to the adoption of a gluten-free diet, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancies. Rates of gastrointestinal cancers are increased in people with Crohns disease and ulcerative colitis, due to chronic inflammation. Also, immunomodulators and biologic agents used to treat these diseases may promote developing extra-intestinal malignancies. Pathophysiology
Genetics
Cancer is fundamentally a disease of tissue growth regulation. For a normal cell to transform into a cancer cell, the genes that regulate cell growth and differentiation must be altered.The affected genes are divided into two broad categories. Oncogenes are genes that promote cell growth and reproduction. Tumor suppressor genes are genes that inhibit cell division and survival. Malignant transformation can occur through the formation of novel oncogenes, the inappropriate over-expression of normal oncogenes, or by the under-expression or disabling of tumor suppressor genes. Typically, changes in multiple genes are required to transform a normal cell into a cancer cell.Genetic changes can occur at different levels and by different mechanisms. The gain or loss of an entire chromosome can occur through errors in mitosis. More common are mutations, which are changes in the nucleotide sequence of genomic DNA. Large-scale mutations involve the deletion or gain of a portion of a chromosome.