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Stanford Medicine


Cancer, Public Health, Science

Research institute or detective agency? Investigating the “perp” known as cancer

Sherlock Holmes2After graduating from college, I accepted a job as a white-collar crime analyst for the Iowa Bureau of Criminal Investigation. It was an exciting first job for a 21-year old. I worked closely with a team of highly trained and dedicated public safety officers to help detect and prosecute white-collar criminals. My specific role was to identify patterns in criminal activity and assist in building a narrative so others could understand how and why the crime was committed.

Little did I know how closely that job would parallel my current one.

Forty years later, I find myself leading a different type of “detective agency,” the Cancer Prevention Institute of California (CPIC). CPIC employs highly skilled researchers who function a lot like private investigators. They are epidemiologists – scientist-sleuths who examine trends and patterns in the population to identify risk factors and causes and effects of disease, and their work is anything but “elementary.”

As curious and persistent as any detective, epidemiologists are driven to solve challenging public-health cases. At CPIC we pursue understanding the traits and tendencies of a particular perpetrator: cancer. For example, our researchers look at how cancers occur geographically, examining incidence and mortality rates by specific regions across California and the U.S.

“Data! Data! Data!” Sherlock Holmes cried impatiently in The Adventure of the Copper Beeches. “I can’t make bricks without clay.” Well, like Holmes, our scientists also need data; lots of it. CPIC maintains the population-based registry of all Greater Bay Area cancer cases, as mandated by California state law. The registry is a deep source of information on the approximately 30,000 new cancer cases diagnosed each year across our nine-county area. To date, more than 850,000 Greater Bay Area cancers have been registered. Through this and other data bases, our researchers are able to “investigate” a wide range of cancers, from the most common to the rarest forms, and examine important evidence linking cancer risk with such factors as race/ethnicity, genes, environment, migration status and lifestyle.

Has our scientists’ sleuthing paid off? Definitely. To illustrate, CPIC’s researchers and their colleagues at the Stanford Cancer Institute (SCI) recently found that a double mastectomy does not improve survival over the less invasive option of lumpectomy plus radiation for the average breast cancer patient, contributing important information for breast cancer patients and their physicians worldwide as they evaluate their treatment options. Research conducted by CPIC and SCI scientists also detected alarming rates of deadly melanomas in Californians, as cited in 2011 legislation that made California the first state to ban the use of tanning beds by minors. CPIC researchers also discovered that California nail salons had higher than expected levels of carcinogens, identifying a need for better health standards.

And, yes, just like Adrian Monk or Colombo, we have some quirky scientists who help make coming to work both mighty interesting and very fulfilling. If you come to visit us at CPIC, you just might spy a rumpled raincoat or two.

Donna Randall, PhD, is Chief Executive Officer of the Cancer Prevention Institute of California.

Previously: Breast cancer patients are getting more bilateral mastectomies – but not any survival benefit, Gel polish: What risks lie beneath painted beauty? and New law: No more tanning beds for California teens
Photo by dynamosquito

Cancer, Research, Stanford News, Surgery, Women's Health

Breast cancer patients are getting more bilateral mastectomies – but not any survival benefit

Breast cancer patients are getting more bilateral mastectomies - but not any survival benefit

woman looking out window2The most common cancer diagnosis you or a woman you love is likely to receive is early stage breast cancer, probably after detection by mammogram. One would think that given the regularity with which it’s diagnosed, treatment options for early stage breast cancer would be streamlined. Unfortunately, this isn’t the case.  There’s a staggeringly large menu of potential surgeries and treatments from which a patient and her doctor must choose, each with their own risks and benefits. Not including all of the different hormone blocking and chemotherapies, patients must pick one of three surgeries, shown here in order of escalating invasiveness and risk of complication:

  • Breast-conserving surgery (removal of the tumor only), followed by radiation
  • Single mastectomy (removal of the entire affected breast and any affected lymph nodes)
  • Bilateral mastectomy (the above plus the the unaffected breast)

One also would assume that the medical evidence base providing the benefits to the risk/benefit equations for each surgery would be large and up-to-date. Surprisingly, it is not. The randomized trials comparing lumpectomy and single mastectomy were conducted 30 years ago, and they showed similar risks of death. There has not been (and probably will never be) a randomized trial comparing bilateral mastectomy to one of the less invasive choices for healthy women. Angelina Jolie and other women positive for the breast cancer genes (BRCA1 and BRCA2) are in a different situation. For these women, clinical studies have observed a survival benefit after prophylactic mastectomy. For the 99 percent of women without mutations in these or other high-risk genes, existing trial data do not speak to current trends.

Even after accounting for [numerous factors], we found no evidence of lower mortality for women who had bilateral mastectomy in comparison to breast-conserving surgery

The complexity of choosing a breast cancer surgery – and how evidence should play into that choice – has been a hot topic in the last two months, after the publication of a large study calculating (based on predictive models) that bilateral mastectomy ultimately provides little to no improvement  in life expectancy as compared to a single mastectomy. Soon thereafter, on the New York Times’ opinion page, journalist Peggy Orenstein discussed the emotional reasons why women remove their remaining healthy breast, but firmly labeled bilateral mastectomy as  the wrong approach to breast cancer, saying, “It’s hard to imagine… that someone with a basal cell carcinoma on one ear would needlessly remove the other one ‘just in case’ or for the sake of ‘symmetry’.” Other journalists shared why they chose bilateral mastectomy knowing that it wouldn’t necessarily save their life.

To improve the evidence regarding outcomes after the three surgery types, our team at the Stanford Cancer Institute and the Cancer Prevention Institute of California used one of the largest cancer databases available: the cancer registry for the entire state of California. We tracked all 189,734 women diagnosed with stages 0-III breast cancer from 1998-2011 to learn which surgeries they were undergoing for breast cancer treatment and how long they survived afterwards.  These are all women who should have been eligible for breast conserving surgery with radiation. Our results were published today in the Journal of the American Medical Association today and have already received media attention.

We found that bilateral mastectomy for early stage breast cancer increased from 2 percent in 1988 to more than 12 percent in 2011.  The rate of increase was fastest among women younger than age 40 at diagnosis, among whom over one-third of those diagnosed in 2011 had a bilateral mastectomy. Bilateral mastectomy was more often chosen by non-Hispanic white women, those with private insurance, and those who received care at a National Cancer Institute-designated cancer center; while unilateral mastectomy was more often chosen by non-white women and those with public/Medicaid insurance. Even after accounting for characteristics of the women themselves, their tumor types, and their hospitals, we found no evidence of lower mortality for women who had bilateral mastectomy in comparison to breast-conserving surgery. Surprisingly, we found that women who underwent unilateral mastectomy had higher mortality than those who had the other two surgery types. We concluded that despite the growing popularity of bilateral mastectomy, it likely does not provide a better outcome than a less invasive procedure.

These data and the public response to them underscore the need for more updated and more personalized information regarding outcomes after common surgeries. Ideally, these would be accessible real-time by patients and their doctors in easily-understood formats.

Christina A. Clarke, PhD, is a Research Scientist and Scientific Communications Advisor for the Cancer Prevention Institute of California, and a member of the Stanford Cancer Institute.

Previously: At Stanford event, cancer advocate Susan Love talks about “a future with no breast cancer”, Exploring the reasons behind choosing a double mastectomy and Researchers unsure why some breast cancer patients choose double mastectomies
Photo by Alex

Cancer, Dermatology, Public Health, Research, Stanford News

Melanoma rates exceed rates of lung cancer in some areas

Melanoma rates exceed rates of lung cancer in some areas


Californians, step away from the beach and grab a hat and sunscreen. Our team of researchers from the Cancer Prevention Institute of California/Stanford Cancer Institute released a new report (.pdf) this week documenting the rapidly growing burden of melanoma in Marin County, California. This small, homogenous (and wealthy) county just over the Golden Gate Bridge from San Francisco has been the focus of cancer studies before, as high rates of breast cancer were first reported there in the late 1990’s (rates declined there as in the rest of the country in 2003 when women stopped taking hormone therapy).

Our most recent cancer registry data show that rates of malignant melanomas in Marin County are 43 percent higher than the rest of the San Francisco Bay Area and 60 percent higher than other parts of California among non-Hispanic whites, who because of their fairer skin tones are diagnosed with melanoma at 20-30 times the rate of other ethnic groups. Also of concern is that the death rate due to melanoma is 18 percent higher in Marin whites than whites in other regions, a significant difference not seen before. Most of the elevated rates are limited to persons over age 65, especially men.

The Bay Area news media reported our findings as front-page news. Most coverage centered on the question of why the rates are so much higher in Marin County. Our best guess is that the higher average socioeconomic status of its residents corresponds to a higher proportion of people with the known risk factors for melanoma: fair complexion (pale skin, blonde or red hair, blue or green eyes) and a history of “intense intermittent” sun exposure over their lifetimes (exposure in big doses like you might get on a beach vacation in the winter).

However, it is also likely that better access to health care and skin screening has resulted in earlier diagnosis, a notion confirmed by the higher proportion of melanomas in Marin County caught when thin and more curable. Local dermatologists reacted to the statistics with some surprise, but didn’t change their standing advice regarding skin cancer prevention: talk to your doctor about skin screening and stay sun safe by wearing hats, long-sleeves and broad-spectrum sunscreen during outdoor activities.

One statistic mostly overlooked by the media was our finding that melanoma is now the second most common cancer diagnosed in men living in Marin County, as rates have surpassed those for lung cancer. This pattern is very different than that observed for whites in the US and world, for whom prostate or lung are first, and melanoma is ranked much lower. With one of the most successful public tobacco control efforts in the world, most populations in California have seen rapid declines in the incidence of smoking-related cancers of the lung and respiratory system.

Unfortunately, it seems for older white persons in Marin County (as well as parts of Utah and Hawaii, where smoking rates have also declined), melanoma and skin cancers represent a major—and relentlessly growing—cancer threat. Perhaps putting down the cigarettes was accompanied by more time at the pool or beach without adequate sun protection. Although California was the first state to ban tanning bed use by minors, we should look to Australia and other countries also battling rising skin cancer rates for innovative new policies and strategies for encouraging safe sun exposure in our at-risk communities.

Christina A. Clarke, PhD, is a Research Scientist and Scientific Communications Advisor for the Cancer Prevention Institute of California, and a member of the Stanford Cancer Institute.

Previously: Beat the heat – and protect your skin from the sun, Working to protect athletes from sun dangers, As summer heats up take steps to protect your skin, Stanford study: Young men more likely to succumb to melanoma and How ultraviolet radiation changes the protective functions of human skin
Photo by stefan klocek

Cancer, Public Health, Stanford News

Can repackaging aspirin get more people to take it daily for prevention?

Can repackaging aspirin get more people to take it daily for prevention?

aspirinNot many over-the-counter drugs can substantially improve your health. However, according to the U.S. Preventive Services Task Force, aspirin can reduce the risk of cardiovascular disease for some people. There is also building evidence that daily low-dose aspirin reduces risk of breast cancer, colon and other gastrointestinal cancers, and may even slow down dementia.

When a doctor agrees that the benefits of daily low-dose aspirin outweigh the potential side-effects, aspirin can be an effective, practical and inexpensive way to save lives and save billions in taxpayer-paid healthcare costs. Yet less than 50 percent of those thought eligible to take daily aspirin appear to be doing it. Why?

As a cancer prevention researcher I think a lot about people’s health-related behaviors – and how to change them. What if increasing people’s usage of daily aspirin were as simple as changing the packaging? Now, the only way to buy aspirin is in a bottle, making it hard to remember if you took one each day. What if we put it in a calendar blister pack? What if we made the pills in the shape of a heart to remind you why you are taking it? What if the packaging and marketing encouraged you to bring up aspirin at your next doctor’s visit?

I recently submitted these ideas as part of the Target Simplicity Challenge – a pioneering “crowdsourcing” effort led by Target to identify new ideas for simplifying healthcare. I found out about the challenge on Twitter (thanks, @seattlemamadoc!), typed it up and even shot some video on my iPhone. The judging panel of doctors, designers, marketing executives and other industry experts liked it enough to make it one of eight finalists in the competition. This week I’m off to Target headquarters in Minneapolis to talk more about the idea before the winners are announced later in the month. The grand prizes include the opportunity to work with Target on turning my idea into reality.

And the public got a say, too – as you can read about on Target’s site.

We need to stop and think about the easiest and simplest ways possible for people to take advantage of existing scientific evidence that will make them healthier. Doctors and medical researchers should work together with experts in design and marketing to identify more evidence-based opportunities to make prevention and healthcare simpler.

Aspirin is inexpensive and available widely over the counter, but still, we could make it easier to take for those people who could benefit. Short of legislating aspirin counseling (a good idea opined in the New York Times), we need fresh and exciting approaches. I really think better design will increase the appeal of daily aspirin for chronic disease prevention and hope I have the chance to find out.

Christina Clarke, PhD, MPH, is a research scientist at the Cancer Prevention Institute of California (CPIC) and a member of the Stanford Cancer Institute. Part of the Stanford Cancer Institute, the Cancer Prevention Institute of California conducts population-based research to prevent cancer and reduce its burden where it cannot yet be prevented.

Previously: Another big step toward building a better aspirin tablet and New research shows aspirin may cut melanoma risk
Photo by brxO

Cancer, Public Health, Women's Health

Gel polish: What risks lie beneath painted beauty?

Gel polish: What risks lie beneath painted beauty?

nail uvThe desire for beautiful nails has fueled an entire industry of nail salons and inspired new trends in nail care. In my work with the Cancer Prevention Institute of California and the California Healthy Nail Salon Collaborative, I have studied and talked at length about the dangers posed by substances used at nail salons.

Gel polish is the current rage, supposedly offering the long wear of acrylic nails without the accompanying nail damage. Gel polishes are popular because the coating is thinner and looks more natural, there’s no dry-time or smudging, and the nails stay shiny and chip-resistant for weeks. This seems like the ultimate nail dream for salon-goers.

If this sounds almost too good to be true, though, it may be – because this latest beauty treatment carries with it a number of potential health risks.

First, these “no-chip” nails are actually a form of artificial nails, so the same chemicals used in acrylic nails are also used in gel polishes. Of great concern are the acrylates, which are individual chemical molecules (or monomers) that bind together (in a process called polymerization) to form plastic materials. Acrylates can cause allergic and irritant reactions. Contact dermatitis, which includes skin itching, burning, scaling, hives, blistering, and even eczema, has been shown to be associated with these compounds in salon workers as well as salon customers. So if customers and salon workers have had problems with acrylic nails, they will also have problems with gel polishes.

Second, the gel process involves applying pre-mixed gel acrylic to the natural nails, followed by curing the nails under UV light after each coat. The acrylic polymer is crosslinked by the action of the UV light. There are about three separate coats of gel, with each coat followed by 2-3 minutes of curing under the UV light.

UV light is a known human carcinogen, with skin cancer being the biggest concern. Dermatologists have cautioned against the regular use of gel polishes due to UV light exposure, however low.

One research study downplayed the risk of the low exposure, with the investigators stating “that a salon client would need approximately 250 years of weekly manicures that involve the use of UV nail lights to develop the same risk of exposure as just one round of phototherapy sessions.” This comparison of UV light used in nail salons to phototherapy devices such as those used in tanning beds, however, doesn’t take into account the fact that UV light is used with chemicals in gel polishes. There has yet to be research about what the health effects may be when harmful chemicals are used in conjunction with the UV light used in nail salons, so it would be contributing to a false sense of consumer security to make these types of direct comparisons. The jury is definitely still out on the safety of gel polishes with respect to cancer risks.

Continue Reading »

Cancer, Genetics, Stanford News

Door dings and DNA – connecting behavior and the environment to your health

Sitting most of the day? Eating poorly? Not sleeping well? Stressed out? These behaviors could be affecting your health—and your DNA.

Think of your body like a car. Sometimes you drive too fast, scrape against a curb or neglect to change your oil at the scheduled time. This behavior may result in minor cosmetic or mechanical “dings” to your car. The environment you drive in, including harsh weather, pothole-littered roads and crowded parking lots may, through no fault of your own, also result in damage to your car. Think about it: How many behaviorally or environmentally caused dings does your car have?

Now, can your environment and behaviors cause analogous dings to your DNA that alter your cancer risk? You are born with your DNA, so it is not something you can change, but you may be able to modify it in important ways. Research shows that through your behavior and environment, your DNA collects imperfections, some of which you may be able to repair through healthy behavior.

In more scientific language, there are epigenetic modifications that do not change the DNA sequence but are layered on top and alter gene expression and protein levels to produce positive and negative impacts on your health. Harmful protein levels may be the result of these dings to your DNA: added negatively acting epigenetic modifications or removed beneficial ones. Protein levels are important, as too much of some or too little of others may cause cells to behave improperly. These imbalances and subsequent cellular behaviors are something researchers are exploring as possible causes for cancer and a variety of other diseases.

Some of your epigenetic modifications (good and bad) may be inherited and perhaps this is part of the reason why cancer, heart disease and Alzheimer’s often run in certain families. As you can imagine, there is great interest in whether and exactly how environment or lifestyle choices such as diet, exercise, sleep and stress levels impact our disease risk. High-fat diets, for example, are fairly consistently associated with cancer, and often with more aggressive cases. Evidence exists suggesting that certain fat by-products impact protein expression in specific pathways related to cancer development. It is possible that high-fat diets epigenetically alter your DNA in a negative fashion leading to cancer – the “you are what you eat” adage may be more prophetic than we thought.

The good news is that just as you can take your car in to get some of the dings cleaned up, you can likely alter your DNA in positive ways through good epigenetic modifications. It may be possible, for example, to exercise regularly or eat certain foods and mitigate some inherited or lifetime-incurred epigenetic modifications. For those of us interested in gene-environment interactions, this is an opportunity to explore how lifestyles and environments modify health through molecular-level DNA alterations. Understanding which of these “dings” cause disease and how we can reduce them will allow us to connect behaviors and environment to their biological manifestations and ultimately reduce disease risk.

Ingrid Oakley-Girvan, PhD, MPH, is a research scientist at the Cancer Prevention Institute of California and a member of the Stanford Cancer Institute. Watch Ingrid’s video on Door Dings and DNA here.

Cancer, Research, Stanford News

Apple- or pear-shaped: Which is better for cancer prevention?

We always want what we don’t have. My teenage daughter is tall and beautiful (in my naturally biased and loving view). But she’s always complaining about her thighs. She thinks they’re too big and don’t look good in skinny jeans. What I see is a young girl with a fresh face, beautiful curves and a youthful spring of energy.

As a molecular epidemiologist, I see one more thing. She has a so-called “pear-shaped” body, which means she has larger thighs relative to a smaller waist, with most of her fat deposited in the lower body. In contrast, people who have “apple-shaped” bodies are heavier in the middle and have their body fat accumulated around the waist, closer to the heart, putting them at a higher risk for abdominal obesity. Many studies have shown that abdominal obesity has a more detrimental effect than overall obesity (as measured by body mass index, the metric calculated using height and weight) on a number of diseases, including type II diabetes, cardiovascular disease and certain cancers (such as those of the breast, ovary, gallbladder and kidney). The specific biological mechanisms are not entirely clear, but we do know from recent research that fat (adipose tissue) is an endocrine organ that actively secretes a variety of chemicals, such leptin, adiponectin, estrogen and other hormones, and inflammatory cytokines. These markers have been linked to growth and proliferation of cancer cells.

The Stanford Cancer Institute and its affiliated research partner, the Cancer Prevention Institute of California (CPIC), currently are conducting studies to understand more clearly the molecular mechanisms underlying the adverse effects of abdominal obesity on cancers. A better understanding of how leptin and inflammatory markers associated with abdominal obesity can influence cancer risk at the molecular level will help clarify the specific steps involved in carcinogenesis, which in turn can aid the development of effective preventive strategies to stop or slow down cancer development.

Our genetic makeup determines largely which body type we are born with, pear or apple. But our eating habits, physical activity and weight management can also affect fat distribution and disease susceptibility. Regular exercise (three times a week) helps increase muscle mass, which in turn can enhance metabolism and lower the risk of metabolism-related conditions, including certain cancers. Whether cancer prevention and weight reduction guidelines differ for those with different body types is another important topic for future studies.

My daughter is the apple of my eye. But I’m glad that, unlike me, she’s a pear. She inherited her father’s body type. In theory, her risk of certain hormone-related cancers or metabolic disorders is lower than mine. So next time she complains about her thighs, I’ll share with her my recent work on abdominal obesity and cancer and try to convince her that she’s lucky to have “big” thighs.

Ann Hsing, PhD, MPH, is director of research for the Cancer Prevention Institute of California (CPIC). Part of the Stanford Cancer Institute, the CPIC conducts population-based research to prevent cancer and reduce its burden where it cannot yet be prevented.

Photo by KDL Designs

Cancer, Research, Science, Stanford News, Women's Health

The future of preventive medicine is in the freezer

The future of preventive medicine is in the freezer

…Make that lots and lots of freezers.

Freezers storing blood from thousands of generous research volunteers who donate samples when they are healthy – years or even decades before they might develop cancer, diabetes or other chronic diseases – can be found across the country. For scientists, these “pre-diagnostic” blood samples are likely to contain new biological clues of disease, perhaps molecular flags that cancerous cells are multiplying, or immunological rumblings as the immune system responds to the first signs of disease. Finding these signals is critical to future prevention, as they could represent the basis for blood tests or other means of ultra-early detection of disease.

The statistics involved in gathering enough pre-diagnostic blood samples to make them useful to research are daunting, though. For example, to study the blood of 100 women who go on to develop ovarian cancer in the next year, more than 200,000 samples from healthy women must first be stockpiled.

This month, Stanford’s partner, the Cancer Prevention Institute of California, along with their colleagues in Southern California at the City of Hope National Medical Center and UC Irvine, embark on an epic research effort: asking more than 50,000 female teachers, retired teachers and school administrators all over California – participants for the last 16 years in the long-term follow-up California Teachers Study – to provide a blood sample to be stored away for future research. This is no small logistical feat. First, teachers aged 50 to 79 from all over the state will be asked to participate and provide a convenient time and place for a phlebotomist to visit them for a blood draw. The samples will then be express shipped to a state-of-the-art biobank where they will be frozen in large banks of closely monitored freezers, alongside similar samples from other long-term studies.

The Teachers Study will continue its long-standing routines for tracking the health outcomes of each participant by continuously linking their names and other identifying information to California health databases, including death certificates, cancer registries and hospitalization discharge summaries. With time, the stored blood samples will turn into scientific gold, as we learn which of them were drawn from women who later developed cancer. In addition to looking for early proteomic markers of breast, ovarian and other cancers, the samples of women who ultimately developed cancer will undergo intense testing for chemical pollutant levels.

DNA will also be extracted from the blood, and from saliva samples donated by mail from teachers who live too far from the phlebotomists’ routes, or who volunteer to participate in that way. These DNA samples will likely be analyzed with others from very large prospective studies, like the ongoing study of more than 100,000 Northern California Kaiser Permanente members, whose saliva samples have been banked.

Some new clues to cancer can only be discovered when scientists study massive numbers of samples at the same time. To date, gene hunting has yielded a few blockbuster findings – most famously the rare BRCA1 and BRCA2 genes with very high risk for breast cancer – but no common genes or gene combinations amenable to broader risk profiling. This may be because past efforts didn’t have the statistical power to find the most likely culprits, subtle combinations of many gene mutations that together may provide some meaningful differentiator of risk. Very large datasets, containing not thousands but millions of genomes, will be required to establish reliable genomic markers of disease.

Genomic prediction for chronic disease and ultra-early blood tests for cancer aren’t here yet, but they’re getting closer. And when they do arrive, we can thank the volunteers with the foresight to file away their precious blood samples in many, many freezers.

Christina Clarke, PhD, MPH, is a research scientist at the Cancer Prevention Institute of California (CPIC) and a member of the Stanford Cancer Institute. Part of the Stanford Cancer Institute, the Cancer Prevention Institute of California conducts population-based research to prevent cancer and reduce its burden where it cannot yet be prevented.

Photo by Shutterstock

Cancer, Nutrition, Research, Sleep

It's true: Grandma knows better than a molecular cancer epidemiologist

It's true: Grandma knows better than a molecular cancer epidemiologist

Every two weeks, I call my 99-year-old grandmother in Taiwan on Skype. And every time she repeats the same message before we sign off: “Eat well, sleep well, don’t work too hard.” This is exactly what she used to say to me when I was a child growing up in Taipei. Now, fifty years later and halfway around the world, she repeats the same advice to me as if I were still a little girl.

As much as I respected her, for most of my adult life I considered my grandma’s words a well-intentioned old wives’ tale. I am a woman of science, after all – a molecular epidemiologist who has devoted her life to cutting-edge cancer research. I believe in data, not proverbs.

Of course, it turns out that Grandma was right. I am now aware of abundant data suggesting that eating and sleeping well boost our immune function, minimize harmful inflammatory conditions and regulate hormonal metabolism, thereby lowering our risk for cancer.

Epidemiological studies suggest that consuming whole grains (containing fiber and vitamins), fruits and vegetables (antioxidants, fiber, and specific compounds such as sulforaphane in cruciferous vegetables), tomatoes (lycopene), allium vegetables such as garlic and chives, tofu (isoflavones) and fish (the omega-3-containing varieties) reduces the risk of cancer. Research also suggests that eating foods high in certain chemicals, such as heterocyclic amines found in some grilled foods, increases the risk of cancer.

Although we are still learning about the specific biological mechanisms underlying these epidemiologic findings, ongoing studies, including those at the Stanford Cancer Institute and the affiliated Cancer Prevention Institute of California (CPIC), are revealing the molecular relationships between dietary components and cancer risk.

The value of getting to sleep early (before 11 p.m.) and sleeping well long escaped the attention of scientists. I first became interested in sleep as a risk factor for cancer when epidemiologic studies began to show that rotating-shift workers have a higher risk of endocrine-related malignancies, including breast and prostate cancers.

Over the last seven years, my research group has investigated the association of circadian rhythms, including sleep duration, serum melatonin, and 9 circadian core genes, with prostate cancer risk. During the same period, laboratory studies have shown a link between circadian rhythms and inflammation. The numbers of different immune cells (e.g., “T-cells” or natural killer cells) have been shown to peak during different parts of the sleep/wake cycle. We have found evidence that several risk factors that appear to be related to inflammation – including gallstones, obesity, and diet – are risk factors for cancers of the prostate, gallbladder and liver.

While I and other researchers continue our quest to understand the molecular steps involved in carcinogenesis and design the most effective interventions and medicines for cancer prevention, it is clear that we can behave better to reduce our cancer risk – even without knowing the detailed biological pathways – through a sensible lifestyle. My 99-year-old grandmother, who loves broccoli but doesn’t know anything about DNA methylation, is living proof. And her habits reveal a lot: She rises each day at 5 a.m. and is asleep at 11 p.m.; she eats three small meals daily, at exactly the same time; and she has a cup of coffee (containing phenols) every day at 3 p.m. My grandma believes that having healthy habits improves life, and I now have the data suggesting that they decrease cancer risk and improve life expectancy, as well.

Before I ever studied the role of circadian rhythms in cancer, my grandmother knew that sleeping well was good for her health. So I’m looking forward to my next conversation with my grandma. Perhaps if I listen well, I’ll find another pearl of wisdom that leads to my next research project.

Ann Hsing, PhD, MPH, is director of research for the Cancer Prevention Institute of California (CPIC). Part of the Stanford Cancer Institute, the CPIC conducts population-based research to prevent cancer and reduce its burden where it cannot yet be prevented.

Cancer, Immunology, Stanford News

Cow manure, coughing co-workers and cancer prevention

Kids home from school, empty cubicles at work… Why all the coughing and sneezing this fall, even before the really cold, wintery time of year? The timing relates to kids having gone back to school, where germs are passed easily among kids and then on to their working parents, who then import them to the office, laying the groundwork for germ transportation all winter long. It’s enough to make you want to hole up in a Cloroxed linoleum closet with a big bottle of Cipro and a fire extinguisher full of Purell.

But what if living in a superclean environment actually makes you sick, or increases your risk of cancer? It’s now clear that highly hygienic environments, especially in infancy, play an important role in the skyrocketing occurrence of asthma, allergies and autoimmune disease.

The “hygiene hypothesis” was first raised in 1989, when British doctors noticed a lower rate of hayfever among children who had more siblings. Later studies showed reduced risk of asthma, allergies and autoimmune diseases among children with more intense or richer exposures to microbes, including larger family size, time spent near horses, livestock, or stables, and number of household pets. Rates of allergy and leukemia are 30-50 percent lower among children who attend daycare than those who don’t. And more recent data suggest that celiac disease is more common among children born in the summer, when needed exposure to seasonal germs might be lowest.

Ongoing research being conducted at Stanford and the affiliated Cancer Prevention Institute of California is focused on whether these kinds of associations also hold for adult diseases linked to chronic inflammation, not just allergic and autoimmune conditions but deadly breast and colon cancers.

Modern urban life radically reduces exposure to microbes and parasites that have been part of the human ecosystem for eons. These microbes not only include the bacteria and viruses that make you sick, but also those that don’t, including friendly bacteria like lactobacillus that live in your gut, and other benign microbes that live in dirt and untreated water. Parts of dead microbes are probably also important. The immune system is known to be stimulated by the inhalation of bacterial cell wall components called “endotoxin” that become airborne as cow manure or dog poo dries up. Exposure to cow manure may explain why dairy farmers have substantially lower rates of lung cancer despite smoking.

It is biologically reasonable that microbial exposures might influence cancer and inflammatory diseases. In evolutionary terms, the removal of many of these microbes from daily life in the last two generations is very sudden. It is reasonable that babies’ new immune systems may need these microbes to calibrate themselves, so as to respond with the right firepower for the threat at hand. Without adequate calibration, the immune system may overreact to normally safe substances, like pollen, dog fur, or peanuts, or get stuck in a chronic state of overreaction, causing inflammation. It is also likely that under-exposure to microbes skews gut bacterial ecosystems to create inflammatory immune responses.

Researchers are starting studies to explore how probiotics, or other controlled exposures to microbes, might be new tools for preventing cancer. As this and other studies to understand the lifelong health consequences of the hygiene hypothesis continue, it is unlikely that modern lifestyle preferences will revert back to the muddy and germy. Perhaps there will be evidence someday for controlled exposures to immune-boosting probiotics or benign microbes. But in the meantime, don’t necessarily curse the coughing co-worker or sneezing schoolmate – they may actually be lowering cancer risks for you and your children.

Christina Clarke, PhD, MPH, is a research scientist at the Cancer Prevention Institute of California *CPIC) and a member of the Stanford Cancer Institute. Part of the Stanford Cancer Institute, the Cancer Prevention Institute of California conducts population-based research to prevent cancer and reduce its burden where it cannot yet be prevented.

Previously: Eat a germ, fight an allergy

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