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

…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

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.

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