Detection of cancer at very early stages is very challenging and almost impossible, but prediction of cancer developing is even more difficult. Scientists tried different ways to anticipate cancer based on some changes in blood especially in DNA, proteins, genes, RNA, changes in morphology of organelles, enzymes, hormones and many other patterns that may help in detection or prediction of cancer. Cancer usually shows up its symptoms very late after it has hijacked all the metabolism and created its independent way of surviving.
In this way researchers have discovered an easily detectable, “pre-malignant” state in the blood that significantly increases the likelihood that a person will go on to develop blood cancers such as leukemia or lymphoma later in life. Giulio Genovese, Steve McCarroll, Ben Ebert, Siddhartha Jaiswal and colleagues describe this discovery in two back-to-back papers this week in the New England Journal of Medicine.
Genovese noticed the phenomenon while analyzing exome sequence data from 12,000 Swedish research participants, half of whom were affected with schizophrenia or bipolar disorder. Genovese, who trained as a mathematician before becoming a geneticist, developed ways to identify the subset of mutations that a person had acquired during life, distinguishing them from the far-larger number of “inherited” variants with which a person is born (see Figure). He found that such mutations, rather than being randomly distributed across the genome, were concentrated in four genes – all genes known to be mutated in cancer.
Genovese hypothesized that the mutations reflected cells that had acquired some, but not all, of the mutations require to drive a cell to cancer. The cells, he hypothesized, were in a “pre-cancerous” state – vulnerable to becoming cancerous, but not there yet.
The key question, then, was what happened to these people later in life? Here, the research team drew upon a strength of the Swedish medical system –electronic medical records that allow health outcomes to be used in research, when patients have consented to contributing such data to research. Genovese’s colleague Anna Kahler at the Karolinska Institute in Stockholm searched these records to find out whether the patients developed cancer in the years after their DNA was sampled for the original study. The result was astonishing – carriers of the clones were developing blood cancer at 12 times the normal rate.
The researchers also found that clonal hematopoiesis becomes increasingly common as we age: it is rare (<1%) among the young, but affects 10% of the population over 65 years old.
Jaiswal, Ebert and colleagues discovered the pre-malignant state independently while analyzing exome sequence data from patients with type II diabetes.
Toward early diagnosis and prevention of cancer?
Clonal hematopoiesis might be helpfully compared to colon polyps, the precancerous lesions that arise in the colon when a cell acquires a mutation that causes it to clonally expand. Hematopoietic clone, like polyps, are “precancerous” lesions that arise when a somatic cell acquires a mutation and clonally expands. The cells in polyps have a substantial risk of acquiring additional mutations and becoming malignant. For this reason, adults over 50 have been medically advised to get colonoscopies every 10 years; when colonoscopy identifies a polyp, it is often removed surgically. Such surveillance is reducing the incidence of colon cancer.
Could an analogous system now be developed to prevent blood cancers? “The challenge today is that unlike polyps, which are surgically removed to prevent colon cancer, precancerous blood stem cells are mixed up with the healthy cells,” McCarroll says. “We need to find medical ways to reduce the likelihood that these cells progress to cancer. That kind of research now becomes possible. It is a key research direction, as it could lead to ways for patients to benefit from information about their clones. Great scientists like Ben Ebert will lead the way in this important new research direction.”
But besides DNA changes, proteins also may help in diagnosing and predicting cancer through noninvasive way of blood sample. In this context protein called CA125 was studied as a biological marker for ovarian cancer and it was found that its levels changes a lot in blood of people while they experience cancer compared with nondiseased patients.
Genes are also an unneglectable hallmark in cancer foreseeing .The BRCA gene test is a blood test that may also predict cancer risk through DNA analysis to identify harmful changes (mutations) in either one of the two breast cancer susceptibility genes — BRCA1 and BRCA2.
Also changes in expression of several genes such as: 1). BHLHE40, 2) HSD17B6, 3) CACNA1A, 4) HDAC8,5) DLGAP5,6) KIF2C,7) ZMYND10, and 8) VAV3,was observed in blood samples. The expression of these eight genes was noticed to change in breast cancer and are of high importance for detection, prediction and chemotherapy.
Enzymes are also an important tool for cancer prediction that is proposed from researchers. The test developed by Kansas State University's Bossmann and Troyer works by detecting increased enzyme activity in the body. Iron nanoparticles coated with amino acids and a dye are introduced to small amounts of blood or urine from a patient. The amino acids and dye interact with enzymes in the patient's blood. Each type of cancer produces a specific enzyme pattern, or signature, that can be identified by doctors.
Circulating miRNAs have emerged as a new class of promising cancer biomarkers. Independent studies have shown the feasibility of using these small RNAs as tools for the diagnosis and prognosis of different types of malignancies as well as for predicting and possibly monitoring treatment response. Every tumor has specific RNA that circulates in blood and has its unique shape and morphology.
The theory that telomerase is the culprit in maintaining human cancers was proposed in 1990, but the evidence just recently became persuasive enough. A majority of human cancers exhibit critically short telomeres, suggesting that tumors can arise from genetically instable cells with dysfunctional telomeres. Changes in activity of telomerase and in morphology of chromosome caps is very helpful in prediction or treatment of cancer based on drug therapy and other related nondrug therapies.