News from the Front in War on Cancer--Mission Not Accomplished

Scientific American

Janet Rowley noticed something odd about the glowing chromosomes revealed by her microscope. It was the early 1970s, the first years of the so-called "war on cancer," and she was using a new staining technique to examine cells from patients with chronic myelogenous leukemia (CML), a cancer of the blood that was almost always fatal. The technique highlighted bands within the chromosomes, and she could see an extra piece on the end of chromosome 9. That fragment was nearly the same size as a "missing" chunk of chromosome 22 that other researchers had detected a decade earlier. To Rowley, it looked as if the tips of these two chromosomes had swapped places, or translocated. During the next few years she found two other cases of chromosomal translocation in different forms of leukemia. The finds forever changed the way scientists thought about cancer.

Shuffled chromosomes in leukemia established that broken, scrambled and messed-up genes cause cancer. The genetic code details when cells should grow, divide and eventually die. Cancer is a disease of misinformation—cells ignore the rules, growing despite multiple molecular signals telling them to stop and invading other tissues because they no longer respond to biological messages to stay put or even destroy themselves. In the past four decades scientists have identified thousands of genetic mistakes that either cause cancer or boost the risk of developing it. The effects of these typos are sometimes dramatic—the gene variants BRCA1 and BRCA2 can boost women's lifetime risk of developing breast cancer from 12 percent to 60 percent. Some errors are found only in cancer cells themselves; other changes can be passed from generation to generation. The latter are the mistakes that may be passed down and boost the risk of developing cancer—this is the inherited genetic risk, or the reason that people with a familial history of a disease may want to get tested earlier or more often.

As researchers uncover more genetic mistakes and delve deeper into the human genome, it may be possible to pin down the exact probabilities conferred by inherited genetic risk. If clinicians could scan a healthy person's genes for variations that explain their probability of developing cancer, perhaps they could prevent or catch the disease before it became a problem: Spit into this vial and the doctor will tell you what will ail you in 20 years.

Despite the plummeting cost of DNA sequencing technology, much of the information is a jumble of alphabet soup. Science can figure out what gene variants and markers a person has, but they can't tell exactly what it means for his or her health. It will take researchers years to untangle the genetics of cancer. Even large steps, heralded as a major advances, answer few questions and pose many more.

This spring, a massive international collaboration doubled the number of known genetic regions associated with the risk of breast, prostate or ovarian cancers. The genetic markers are signpost that researchers can follow to better understand the biology of these cancers. Only a few of the 74 newly identified markers are shared by more than one type of cancer, underscoring cancer's complexity. Yet exactly how the findings can inform public health recommendations remains to be discovered. Each marker is associated with small modifications of risk, but the effects add up. The findings could lead to more accurate cancer screening and hint at ways cancers could be caught before the disease becomes aggressive. Only further study, however, will show where to draw the lines between risk percentages that tell patients "not to worry" or "get tested now."

Reams of data

The impressive number of hits in the new work stems from the size of the research effort: 160 institutions around the world analyzed a pool of more than 200,000 individuals' genetic sequences. The international project is called the Collaborative Oncological Gene-environment Study (COGS). To find the dozens of new cancer risk regions, researchers combed the pooled genetic information for variations called single-nucleotide polymorphisms (SNPs). A SNP is change in a single letter of the DNA code, likely introduced as a "typo" during gene replication. If such a change happens within a gene, it can affect the structure of proteins. If it falls within a stretch of DNA that regulates genes, it can affect the amount of protein a cell produces.

The COGS researchers put 211,000 SNPs of interest, which were previously identified in other studies, on a custom-made DNA array that looks a bit like a computer chip. Then they used the chip to scan the pooled genetic information to look for differences between people who had cancer and those who did not. If a particular SNP popped up more often in the group of people who had cancer, that SNP could be linked to increased risk for that cancer.

Most of the SNPs the cancer teams identified are specific to one of the three cancers, but 17 are shared risk factors for all three. The new SNPs, combined with 75 previously known markers, explain a proportion of inherited genetic risk for these cancers: 28 percent for breast, 4 percent for ovarian and 30 percent for prostate cancer. The research was published as a collection of 13 papers in April in Nature Genetics, Nature Communications, PLoS Genetics, The American Journal of Human Genetics, and Human Molecular Genetics (Scientific American is part of Nature Publishing Group).

Comparing genomes to uncover SNPs of interest is one way that researchers dig down to find the genetic basis of complex diseases. "We get little bits that we put together," says Stephen Chanock, chief of the Laboratory of Translation Genomics at the National Cancer Institute. Chanock was involved in several of the new studies. Complex diseases such as cancer spring from many gene variants that all contribute to the disease. These studies are helping researchers fill in the list of risky genetic markers. "What is emerging is the complicated genetic architecture of different diseases," he says.

Following the signs

Rowley's swapped chromosomes eventually led researchers to find a way to treat CML. Now patients can take a pill that jams a monkey wrench into a process vital to the cancer's development. The drug, called imatinib (first marketed as Gleevec in the U.S.), often grants patients a normal life expectancy with minimal side effects. Few cancer treatments have met this high bar, but researchers still comb the genome for cancer's fingerprints and clues to what might stop the disease.

Indeed, the COGS findings provide signposts for future research. For example, a handful of SNPs associated with prostate cancer risk fall within genes important for the binding of a cell to a surface. That surface could be another cell to facilitate communication or create a barrier through which pathogens cannot pass. Cell–cell adhesion is important for immune response and is also involved in tumor metastasis—tumor cells use cell adhesion to stick to a new location in the body. Understanding the mechanisms for cell–cell adhesion may offer insights for new treatments.

In a number of regions the SNPs are involved in more than one type of cancer cluster. "In some cases we are beginning to understand why that is," said Doug Easton, a professor at the University of Cambridge and the lead author of the main breast cancer paper at a press conference before the papers were published. One of the COGS papers honed in on a genetic region that helps control the length of telomeres, which are protective caps on the end of DNA strands. The so-called TERT locus harbors SNPs relevant to both breast and ovarian cancer risk, making it a prime candidate for further study.

The next step for the international cancer teams is an even larger study with a new chip called OncoChip, made by Signature Genomics. They plan to screen 600,000 SNPs of interest to see if they are involved five malignancies—ovarian, breast and prostate as well as colorectal and lung cancers. The larger numbers will give the researchers more statistical power to uncover less common gene variants. In addition researchers will map the already discovered variants to figure out which genes and biochemical pathways are involved. Studies of gene function are critical to characterize cancer biology, says Mathieu Lupien, a scientist at the Ontario Cancer Institute and assistant professor at the University of Toronto who was not involved in COGS. "Now we can move forward and understand why it is those genetic defects promote cancer," he says.

Weighing the risks

Genetic markers may lead to better treatments, but researchers also hope to catch cancer before it starts.

Clinicians already use cancer-risk calculators to group people into high- and low-risk categories based on lifestyle choices, environment and family history. The new SNPs could be additional indicators that make the stratification more accurate and efficient. High-risk groups could get targeted recommendations for avoiding risky behaviors or whether to get screened for a type of cancer.

Currently, cancer screening is saddled with a lot of false positives, which means people who do not have cancer are told they are positive. Such results lead to unnecessary and even dangerous procedures—not to mention the anxiety felt by those who believe they have a potentially life-threatening disease. For example, screening for prostate, lung, colorectal and ovarian cancers in 68,436 people over a period of three years led to a least one false positive for 60 percent of men and 49 percent of women. Another study found that follow-up procedures (such as a biopsy) after a false positive cost an average of $1,024 for women and $1,171 for men. The challenge is figuring out where to draw the line for high-risk, says Ros Eeles, a professor of oncogenetics at the Institute of Cancer Research in London and one of the principal investigators involved in the main prostate cancer paper. "We could do the test and give a risk profile, but we don't know what you should do when you have the information," she says. Studies that retroactively profile genetic risk markers in patients could reveal where the lines should fall and what interventions are most effective.

"We're not to the point of being able to predict an individual's risk," says Joe Gray, a professor at Oregon Health & Science University's Knight Cancer Institute and not involved in the COGS studies. A more thorough understanding of risk factors and better cancer screening could lead to a future where doctors can "prevent people from having cancer we don't know how to treat," he says.

More information about how different genetic variants contribute to risk of disease could help refine the definition of high-risk groups. A well-tested SNP profile could sort out individuals at the top of the spectrum, where the benefits of screening would outweigh the risks. Once the genetic risk is understood, public health professionals can employ the same communication strategies used to counsel people about heart disease risk. "We do [stratified screening] all the time with cardiovascular risk," says Hilary Burton, director of the PHG Foundation based in England. Right now the evidence on breast cancer screening is "finely balanced between benefits and harm," she says. The newly identified SNPs can help tip the balance for some carefully identified individuals.

The vision the researchers outline could be in the not-too-distant future. People in their 40s today might see safer, stratified risk screening for some cancers within their lifetimes, Cambridge’s Easton said in a press conference. Still, before all patients can receive the benefits of safe screening, researchers will need to address a gap common to current genome-based discoveries: The 200,000 people in the COGS pool are largely of European descent and live Australia, North America and Europe. Whereas the consortium did find some risk markers specific to people of Asian descent, other genetic groups such as African and indigenous populations in the Americas and Australia are underrepresented.

"We are still very much in the discovery mode," Chanock says. Decades after uncovering the genetic basis of cancer, that is a sobering statement.

Follow Scientific American on Twitter @SciAm and @SciamBlogs.

Visit ScientificAmerican.com for the latest in science, health and technology news.

© 2013 ScientificAmerican.com. All rights reserved.

Sorry you didn't like this comment. Please provide a reason below.

Are you sure?
Rating failed. Try again.
Request failed. Try again.
We will promote constructive and witty comments to the top, so everyone sees them!
Sorry, we can’t load comments right now. Try again.

    Recommended for You

    • The internet roasts a photo of Donald Trump writing his inauguration speech

      When times get tough, at least you can still meme. President-elect Donald Trump is slated to deliver his inauguration address on Friday, so he teased his Twitter followers with a little behind-the-scenes photo of himself writing a speech at his Mar-a-Lago estate in Florida. SEE ALSO: Don's Johns: Port-a-potties get censored for Trump’s inauguration Writing my inaugural address at the Winter White House, Mar-a-Lago, three weeks ago. Looking forward to Friday. #Inauguration pic.twitter.com/S701FdTCQu — Donald J. Trump (@realDonaldTrump) January 18, 2017 The staged photo and Trump's cold, dead gaze sent the internet straight into "meme mode alpha," where it was pointed out that Trump was actually holding Sharpie marker, which may or may not actually be closed. @realDonaldTrump that is a blank piece of paper and you're holding a closed sharpie pic.twitter.com/ekCcH8eTXe — Jules Suzdaltsev (@jules_su) January 18, 2017 @cajunmonkey439 @realDonaldTrump It is *obviously* a sharpie. pic.twitter.com/gdD2AUhBKX — Jules Suzdaltsev (@jules_su) January 18, 2017 .@realDonaldTrump pic.twitter.com/8CSroNshBR — XpeK (@peKofX) January 18, 2017 Surprised that you didn't just use this photo as your epic, bigly speech pic.twitter.com/SezwzToFg4 — Roland Scahill (@rolandscahill) January 18, 2017 good job @realDonaldTrump pic.twitter.com/Ioj869Tfy3 — uhhh (@_uhhhhhhh) January 18, 2017 pic.twitter.com/pAKcXAEAkD — Sam Grittner (@SamGrittner) January 18, 2017 @realDonaldTrump #NotMyPresident #TheResistance #conflict #Putin #Inauguration In house security cam Mar a Lago pic.twitter.com/diwnpjAS3F — Beo Bachter (@kaysintBB) January 18, 2017 Early draft of Donald Trump’s inauguration speech. #TrumpSpeech #MyFirstWordsAsPresident #MAGA pic.twitter.com/qgo1glv5cG — Tom ❄️ (@TommieWho) January 18, 2017 Exclusive sneak peek at Trump's inauguration speech! pic.twitter.com/6W6ex0Ks3z — Kara Calavera (@KaraCalavera) January 18, 2017 Trump's Inaugural address leaked... pic.twitter.com/J8soJQ4Ira — Jordan Uhl (@JordanUhl) January 18, 2017 Exclusive: #Trump's Inauguration speech leaked! #TrumpInaugural #trumpgrammar pic.twitter.com/XzrXXpnjxD — Gerry Stergiopoulos (@GerryGreek) January 18, 2017 According to CNN, Trump did write his inauguration speech himself. BONUS: NBD, just a massive alligator out for a stroll

      Mashable
    • Foreclosed mall once valued at $190M is auctioned for $100

      TARENTUM, Pa. (AP) — A Pennsylvania mall that was foreclosed on after its owners failed to repay $143 million has been auctioned off for $100.

      Associated Press
    • Ex-president George H.W. Bush moved to intensive care; wife hospitalized

      Bush, who at 92 is the nation's oldest living ex-president, has been at Houston Methodist Hospital since Saturday after experiencing shortness of breath, family spokesman Jim McGrath said on Wednesday. Since then, Bush experienced an "acute respiratory problem stemming from pneumonia" and was sedated for the unspecified procedure, his office said.

      Reuters
    • Giant Florida Gator Is Not For Tourists, Nature Preserve Staff Warn

      Officials for the county's natural resources division said, although, they appreciate the attention the nature reserve has been getting, they are also worried about the safety of visitors and wildlife.

      International Business Times
    • Virginia man convicted of 2006 slaying of family is executed

      JARRATT, Va. (AP) — A man convicted of killing a family of four, slashing their throats and setting their home ablaze after they left their front door open while preparing for a New Year's Day party in 2006, was executed Wednesday.

      Associated Press
    • Is your diet changing your gut bacteria? (7 photos)

      Did you know you have trillions of bacteria living inside your body right now? And that’s not a bad thing. These bacteria form the microbiome and when functioning well, these little microbes protect you from harmful invaders, help build your immune system, and play a role in vitamin and short chain fatty acid synthesis.  Imbalances in the intestinal microbiome has been linked to the potential for autoimmune disorders, irritable bowel syndrome, irritable bowel disease, cardiovascular disease and even obesity and metabolic syndrome . Research is constantly ongoing and emerging in this field. An interesting fact is that your microbiome is completely different and unique when compared to another individual’s. We are colonized when we are born by the microbes in our environment, then furthermore when we’re exposed to breastmilk or formula, and when we begin to eat solid foods.  Once theory suggests that with the emergence of agriculture, animal husbandry, sanitation, and antibiotics, our microbiome has transformed into one that more easily allows the growth of pathogenic bacteria, resulting in allergies, autoimmune disorders, and irritable bowel disease.  The proposition is that depending upon our environment and what we eat, certain harmful or beneficial bacteria are promoted to grow in the body. To test the effects of diet and environment on gut bacteria, Fillipo et al.  conducted a small study in 2010 comparing the fecal microbiota of European children to the fecal microbiota of children from a rural African village.  The European children. who lived in urban areas in Florence, Italy, had been breastfed for a year and consumed a diet that was high in animal protein, fat, starch, sugar, and low in fibre.  The African children, who lived in rural Boulpon in Burkina Faso, were breastfed for up to two years and consumed a diet low in animal protein and fat, and high in starch, plants and fibre. Their food came from nearby villages and specifically included millet, sorghum, black-eye peas, and vegetables. During the rainy season, these children sometimes consumed small amounts of chicken or termites. The researchers found that the African children had a greater proportion of short chain fatty acid producing bacteria (which are thought to have anti-inflammatory properties) and greater microbial diversity when compared to the European children. The African children also had lower proportions of harmful, diarrhea causing  Shigella  and  Escherichia  bacteria than the European children. Although the study mentioned above is small and research in this area is ongoing, it is widely known that a diet low in processed sugars and high in fibre and plants is associated with lower cholesterol, improved cardiovascular health, improved blood sugar control, decreased inflammation, and decreased risk of certain cancers.  Why not make peace with your body and the microbiome in your gut and try out some of my signature plant-powered meals and snacks below.  For more creative, delicious, healthy, recipes and expert nutrition information, stay connected with me at RADNUT , Twitter , Facebook , and Instagram !

      Robin Arora-Desilet, Yahoo Health & Nutrition Blogger
    • Search Suspended for Dad and 3-Year-Old Son Swept Out to Sea as Wife Looked On

      Authorities had spent 22 hours searching for them by air.

      Inside Edition
    • North Korea's Kim Jong Un Is So Fat He Might Have Hurt His Ankle Again

      Kim's leg injuries have been linked to obesity in the past and recent pictures show the Korean leader appears to have put on extra weight. 

      International Business Times
    • J.K. Rowling has a cutting response to Trump's quote about 'heroes'

      LONDON — It's surely only a matter of time before Donald Trump goes on a wild, 5am Twitter rant about J.K. Rowling. The Harry Potter author has been aiming a steady campaign of social media-based ribbing at the President-elect for a while now — and in the last week her volume of Trump-based burns have really peaked. SEE ALSO: J.K. Rowling just burned Donald Trump for the 2nd time in 24 hours This one started when journalist Daniel Dale shared an extract from Michael Gove's recent interview with Trump. The question was one about heroes. Trump was asked if he has any heroes. Answer: https://t.co/3idRsQFQoN pic.twitter.com/yGyjx1q1Bl — Daniel Dale (@ddale8) January 16, 2017 That's a lot of rambling to pick apart, but — luckily — J.K. Rowling was on hand to condense it into a helpful 140 characters: "Heroes? Me, because I am innately awesome and you can't learn this, but a bit my dad, who must've been kinda ok, cos he made me." https://t.co/WYJQ8chAxd — J.K. Rowling (@jk_rowling) January 17, 2017 Ouch. Throughout the morning, Rowling has continued tweeting about Trump. @jk_rowling it is a sad life when one does not have heroes. — zeckle3 (@zeckle3) January 17, 2017  https://t.co/5z1V1TsYBm — J.K. Rowling (@jk_rowling) January 17, 2017 Almost everyone in Europe dreads the Trump presidency. Everyone, except fascists - @alexmassie in @politicohttps://t.co/EzhdXUkNj4 — J.K. Rowling (@jk_rowling) January 17, 2017 @jk_rowling @alexmassie @politico What if you’re neither dreading Trumps presidency or a fascist? — Luke Parker (@MrLParker) January 17, 2017 Then I want some of what you're smoking. https://t.co/pcXzOf1JZm — J.K. Rowling (@jk_rowling) January 17, 2017 We're calling it: he's going to tweet something negative about Harry Potter any day now.  It's only a matter of time. BONUS: J.K. Rowling weighs in hard on the Donald Trump/Meryl Streep feud

      Mashable
    • Hall of Famer Willie McCovey pardoned by Obama

      SAN FRANCISCO (AP) — San Francisco Giants Hall of Famer Willie McCovey has been pardoned by President Barack Obama on tax evasion charges from 1995.

      Associated Press
    • Commentator: Hillary Clinton is the legitimate president

      HuffPo contributor Alex Mohajer argues that a federal judge should intervene because Russian hackers swayed the election and the popular vote makes Hillary Clinton 'The People's President.' Tucker takes him on in a spirited debate #Tucker

      FOX News Videos
    • Undocumented worker sues San Francisco for violating sanctuary law

      The lawsuit was filed on Tuesday on behalf of Pedro Figueroa Zarceno, 32, in federal court in San Francisco against the city and its police chief for violating his right to due process and breaking an ordinance barring municipal employees from cooperating with federal immigration authorities seeking to deport a person. Figueroa walked into a police station in November 2015 to report his car stolen, according to the lawsuit. The civil action comes as San Francisco and dozens of other U.S. cities face pressure from President-elect Donald Trump, who takes office on Friday, to abandon their policies of limiting cooperation between law enforcement officers and U.S. immigration authorities.

      Reuters
    • One Big Reason Not to Buy Nintendo Switch

      The Nintendo Switch is a pretty versatile gaming machine, but don't count on it replacing your home streaming box anytime soon. According to several reports, Nintendo's $299 portable/home console hybrid won't have any significant entertainment features when it releases on March 3, meaning you'll have to get your Netflix and Hulu fix elsewhere. Business Insider spoke to Nintendo's Kit Ellis, who said that the Switch "won't have many multimedia features at launch." While this doesn't rule out the possibility of popular streaming apps coming to the platform later this year, it seems like you'll be strictly playing games on the Switch on release date (and besides the stunning new Zelda title, there aren't many notable launch games).

      Tech Media Network (Tom's Guide)
    • Cowboys delay talk of Romo's future, likely knowing answer

      FRISCO, Texas (AP) — Those closest to Tony Romo on the Cowboys aren't ready to discuss the future of the Dallas quarterback, probably because they know the likely final answer.

      Associated Press
    • Anger at skeletal sun bears in Indonesian zoo

      Animal rights activists Wednesday demanded the closure of an Indonesian zoo after skeletal sun bears were pictured begging for food from visitors and eating their own dung. The bears at the zoo in the city of Bandung were shown waving their arms in the air inside their enclosure -- with their ribs visible through their fur -- as people hurled food at them. Many of Indonesia's zoos are poorly maintained and there are regular reports of animals dying in captivity.

      AFP
    • Teen Abducted 18 Years Ago Says She Will Have '2 Moms,' but Still Loves Accused Kidnapper

      She says she speaks to the accused kidnapper every day despite the woman's arrest for abducting her 18 years ago.

      Inside Edition
    • Teen Abducted 18 Years Ago Doesn't Want to See Alleged Kidnapper Jailed: 'She Will Always Be Mom'

      'I understand what she did was wrong but just don't lock her up and throw away the key like everything she did was awful,' Kamiyah Mobley said.

      Inside Edition
    • Donald Trump Tells Democrats Boycotting His Inauguration: Give Me Your Tickets

      'I don't want the celebrities there. I want the people there,' Trump spouted.

      Inside Edition
    • Photos of the day — January 17, 2017 (23 photos)

      Impoverished Indian children watch a performance as part of advocacy against child labor in Allahabad, India; women loyal to the Houthi movement parade to show support to the movement in Sanaa, Yemen; and dogs are blessed by a priest outside San Anton Church in the neighborhood of Churriana in Malaga on the day of Saint Anthony, Spain’s patron saint of animals. These are just a few of the photos of the day for January 17, 2017. See more news-related photo galleries and follow us on Yahoo News Photo Tumblr .

      Yahoo News Photo Staff