Poor adolescent diet associated with premenopausal breast cancer

“During adolescence and early adulthood, when the mammary gland is rapidly developing and is therefore particularly susceptible to lifestyle factors, it is important to consume a diet rich in vegetables, fruit, whole grains, nuts, seeds, and legumes and to avoid soda consumption and a high intake of sugar, refined carbohydrates, and red and processed meats.”

– lead author Karin B. Michels, ScD, PhD, professor and chair of the Department of Epidemiology at the UCLA Fielding School of Public Health, Los Angeles

Key points: Women who consumed a diet associated with chronic inflammation  as adolescents or young adults appear to have a higher risk of developing premenopausal breast cancer, as compared with those who had a diet not linked to inflammation.

Background: Researchers used data from 45,204 women in the Nurses’ Health Study II who had completed a food frequency questionnaire in 1998, when they were ages 33 to 52, about their diet during high School. The investigators then assed adult diet by first using a food frequency questionnaire in 1991, when participants were ages 27 to 44, and then every 4 years thereafter. They gave each woman’s diet an inflammatory score using a previously method that links diet with inflammatory markers in the blood.

During 22 years of follow-up, 870 of the women who completed the high school food frequency questionnaire were diagnosed with premenopausal breast cancer and 490 were diagnosed with postmenopausal breast cancer. When women were divided into five groups based on the inflammatory score of their adolescent diet, those in the highest score group had a 35 percent higher risk for premenopausal breast cancer relative to those in the lowest score group. When the same analysis was done based on early adulthood diet, those in the highest inflammatory score group had a 41 percent higher risk for premenopausal breast cancer relative to those in the lowest score group.

I’m Michael Hunter, the Breast Cancer Doctor.

Immunotherapy for Cancer

The latest approval of a cancer drug by the US Food and Drug Administration (FDA) changes the paradigm of cancer treatment — the new indication specifies a genetic defect without any mention of tumor types. It allows the drug to be used in any cancer that harbors the specified genetic defect, wherever the tumor appears in the body.

What: Historically, the US Food and Drug Administration (FDA) has approved cancer treatments based on where in the body the cancer started — for example, prostate or breast cancers. For the first time, the FDA approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.

Details: The new approval is for the immunotherapy pembrolizumab (Keytruda, Merck & Co), which is already approved for use in several different tumor types, including melanoma and lung cancer. But this latest approval covers the use of pembrolizumab in tumors that have microsatellite instability-high (MSI-H) or are mismatch repair deficient (dMMR). These defects are found most commonly in colorectal, endometrial, and gastrointestinal cancers but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland, and other places, the agency notes.

Microsatellite instability & immunotherapy: It’s not just colorectal cancer: The results from that trial showed that patients with colorectal cancer with normal DNA repair (microsatellite stable) had zero response to pembrolizumab, whereas those with MSI and deficient DNA repair had a 50% response rate, she said. In addition, about 20% had stable disease. This is much higher than has been seen with immunotherapy in other tumor types, where fewer than 20% patients respond. But the trial also included patients with any solid tumor and MSI, and these patients also showed the 50% response rate and 20% stable disease results.

Downsides: Common side effects of pembrolizumab include fatigue, itchiness, diarrhea, decreased appetite, rash, fever, cough, dyspnea, musculoskeletal pain, constipation, and nausea. The drugs can also cause serious immune-mediated side effects, including lung, liver, kidney, or colon inflammation, endocrine problems.

Action point: All patients with advanced cancer who have had at least one standard therapy should be tested to see if their tumor harbors these genetic defects.

I’m Dr. Michael Hunter.

http://www.medscape.com/viewarticle/880537

Should doctors prescribe exercise?

“Although the data vary by different cancer types, there is a consistent trend suggesting that moderate daily exercise has a beneficial effect on preventing certain cancers. If you are a reasonably healthy adult, your should exercise regularly.” 

Let’s look at the relationship of exercise and selected cancers. The American Society of Clinical Oncology (ASCO) has done a nice job of summarizing:

Breast Cancer

While the amount of risk reduction varies among studies (20-80%), most suggest that 30 to 60 minutes of moderate to high-intensity exercise per day lowers breast cancer risk. Women who are physically active throughout their life appear to benefit the most, but those who increase physical activity after menopause also fare better than inactive women.1

Colon Cancer

Research suggests that people who increase their physical activity can lower the chance of developing colon cancer by 30 to 40% relative to sedentary adults.1,2 A decrease in colon cancer risk can be achieved regardless of body mass index (BMI) and people who are most active benefit the most. There is insufficient evidence of a protective effect of physical activity on the risk of rectal cancer (a protective effect was seen in some case-control studies, but not in cohort studies).3

Endometrial, Lung and Ovarian Cancer

A handful of studies have suggested that women who are physically active have a 20-40% reduced risk of endometrial cancer compared to those who don’t exercise.1 Higher levels of physical activity seem to also protect against lung cancer (up to 20% reduction in risk), particularly among men.1Although less consistent, research suggests that physical activity possibly reduces the risk of ovarian and prostate cancer.

What about Other Cancers?

While observational data on the benefits of exercise for prevention of the types of cancers listed above are fairly consistent, evidence of the effects of exercise on prevention of any other type of cancer either is either insufficient or inconsistent.2,4

Prostate Cancer

Prostate cancer is one disease in which the data are not consistent, however prostate cancer is a heterogeneous disease and risk factor associations for total non-aggressive disease are different from aggressive / lethal disease. Most population based studies show similar findings, with little effect of exercise on overall incidence of prostate cancer but lower risk of aggressive prostate cancers for those with the highest levels of VIGOROUS activity (rather than any type of activity). In the Health Professionals Follow-up Study men 65 years or older who engaged in vigorous physical activity, such as running, jogging, biking, swimming or tennis at least three hours per week  had a 67% lower risk of advanced prostate cancer and 74% lower risk of fatal prostate cancer.5

Conflicting data for other malignancies

For example, one recent study found no association between physical activity and risk of developing gastric, rectal, pancreatic, bladder, testicular, kidney and hematological cancers.4 In contrast, a pooled analysis of data from prospective trials with 1.4 million participants found that physical activity was linked to lower risk of 13 cancers: esophageal, lung, kidney, gastric, endometrial, myeloid leukemia, myeloma, colon, head and neck, rectal, bladder, and breast.6Interestingly, leisure-time physical activity was associated with a higher risk of melanoma (presumably due to time spent outdoors) and prostate cancer, although it is not clear from these data whether that association was with nonaggressive or aggressive prostate cancer.

While we wait for confirmation and clarity on the role of exercise in preventing all the 200+ types of cancer – should doctors prescribe exercise? The answer is simple: yes, because evidence of the protective role of exercise is already strong for some of the most common cancers.

References

  1. Lee I, Oguma Y. Physical activity. In: Schottenfeld D, Fraumeni JF, editors. Cancer Epidemiology and Prevention. 3rd ed. New York: Oxford University Press, 2006.
  2. Slattery, ML. Physical activity and colorectal cancer. Sports Medicine 2004; 34(4): 239–252.
  3. Pham NM, et al. Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2012 Jan;42(1):2-13.
  4. Friedenreich CM, Neilson HK, Lynch BM. Eur J Cancer. State of the epidemiological evidence on physical activity and cancer prevention. 2010 Sep;46(14):2593-604.
  5. Giovannucci E, Liu Y, Leitzmann MF, et al. A prospective study of physical activity and incident and fatal prostate cancer. Arch Intern Med. 2005; 165(9):1005-1010.
  6. Moore SC, Lee IM, Weiderpass E, et al. Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults. JAMA Intern Med. 2016 Jun 1;176(6):816-25.
  7. http://www.asco.org/about-asco/press-center/asco-resources-media/cancer-perspectives/should-cancer-doctors-prescribe?et_cid=38723632&et_rid=463715101&linkid=Read+more

I’m Dr. Michael Hunter. Of course, the disclaimer: Do not begin an exercise program without input from an appropriate medical professional. Many can simply start with a brisk walk for 30 minutes daily, 5 days per week. Have a wonderful day!

Should doctors prescribe exercise?

young woman running city park

“Although the data vary by different cancer types, there is a consistent trend suggesting that moderate daily exercise has a beneficial effect on preventing certain cancers. If you are a reasonably healthy adult, your should exercise regularly.” 

Let’s look at the relationship of exercise and selected cancers. The American Society of Clinical Oncology (ASCO) has done a nice job of summarizing:

Breast Cancer

While the amount of risk reduction varies among studies (20-80%), most suggest that 30 to 60 minutes of moderate to high-intensity exercise per day lowers breast cancer risk. Women who are physically active throughout their life appear to benefit the most, but those who increase physical activity after menopause also fare better than inactive women.1

Colon Cancer

Research suggests that people who increase their physical activity can lower the chance of developing colon cancer by 30 to 40% relative to sedentary adults.1,2 A decrease in colon cancer risk can be achieved regardless of body mass index (BMI) and people who are most active benefit the most. There is insufficient evidence of a protective effect of physical activity on the risk of rectal cancer (a protective effect was seen in some case-control studies, but not in cohort studies).3

Endometrial, Lung and Ovarian Cancer

A handful of studies have suggested that women who are physically active have a 20-40% reduced risk of endometrial cancer compared to those who don’t exercise.1 Higher levels of physical activity seem to also protect against lung cancer (up to 20% reduction in risk), particularly among men.1Although less consistent, research suggests that physical activity possibly reduces the risk of ovarian and prostate cancer.

What about Other Cancers?

While observational data on the benefits of exercise for prevention of the types of cancers listed above are fairly consistent, evidence of the effects of exercise on prevention of any other type of cancer either is either insufficient or inconsistent.2,4

Prostate Cancer

Prostate cancer is one disease in which the data are not consistent, however prostate cancer is a heterogeneous disease and risk factor associations for total non-aggressive disease are different from aggressive / lethal disease. Most population based studies show similar findings, with little effect of exercise on overall incidence of prostate cancer but lower risk of aggressive prostate cancers for those with the highest levels of VIGOROUS activity (rather than any type of activity). In the Health Professionals Follow-up Study men 65 years or older who engaged in vigorous physical activity, such as running, jogging, biking, swimming or tennis at least three hours per week  had a 67% lower risk of advanced prostate cancer and 74% lower risk of fatal prostate cancer.5

Conflicting data for other malignancies

For example, one recent study found no association between physical activity and risk of developing gastric, rectal, pancreatic, bladder, testicular, kidney and hematological cancers.4 In contrast, a pooled analysis of data from prospective trials with 1.4 million participants found that physical activity was linked to lower risk of 13 cancers: esophageal, lung, kidney, gastric, endometrial, myeloid leukemia, myeloma, colon, head and neck, rectal, bladder, and breast.6Interestingly, leisure-time physical activity was associated with a higher risk of melanoma (presumably due to time spent outdoors) and prostate cancer, although it is not clear from these data whether that association was with nonaggressive or aggressive prostate cancer.

While we wait for confirmation and clarity on the role of exercise in preventing all the 200+ types of cancer – should doctors prescribe exercise? The answer is simple: yes, because evidence of the protective role of exercise is already strong for some of the most common cancers.

References

  1. Lee I, Oguma Y. Physical activity. In: Schottenfeld D, Fraumeni JF, editors. Cancer Epidemiology and Prevention. 3rd ed. New York: Oxford University Press, 2006.
  2. Slattery, ML. Physical activity and colorectal cancer. Sports Medicine 2004; 34(4): 239–252.
  3. Pham NM, et al. Physical activity and colorectal cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 2012 Jan;42(1):2-13.
  4. Friedenreich CM, Neilson HK, Lynch BM. Eur J Cancer. State of the epidemiological evidence on physical activity and cancer prevention. 2010 Sep;46(14):2593-604.
  5. Giovannucci E, Liu Y, Leitzmann MF, et al. A prospective study of physical activity and incident and fatal prostate cancer. Arch Intern Med. 2005; 165(9):1005-1010.
  6. Moore SC, Lee IM, Weiderpass E, et al. Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults. JAMA Intern Med. 2016 Jun 1;176(6):816-25.
  7. http://www.asco.org/about-asco/press-center/asco-resources-media/cancer-perspectives/should-cancer-doctors-prescribe?et_cid=38723632&et_rid=463715101&linkid=Read+more

 

I’m Dr. Michael Hunter. Of course, the disclaimer: Do not begin an exercise program without input from an appropriate medical professional. Many can simply start with a brisk walk for 30 minutes daily, 5 days per week. Have a wonderful day!

Cancer Risk Linked to DNA ‘Wormholes’

What You Need to Know: Single-letter genetic variations within parts of the genome once dismissed as ‘junk DNA’ can increase cancer risk through wormhole-like effects on far-off genes. Researchers found that DNA sequences within ‘gene deserts’ — so called because they are completely devoid of genes — can regulate gene activity elsewhere by forming DNA loops across relatively large distances.

The study, led by scientists at The Institute of Cancer Research, London, helps solve a mystery about how genetic variations in parts of the genome that don’t appear to be doing very much can increase cancer risk.

  • Researchers developed a new technique to study the looping interactions and discovered that single-letter DNA variations linked to the development of bowel cancer were found in regions of the genome involved in DNA looping.
  • Their study, published today in Nature Communications, is the first to look comprehensively at these DNA interactions specifically in bowel cancer cells, and has implications for the study of other complex genetic diseases.
  • The researchers developed a technique called Capture Hi-C to investigate long-range physical interactions between stretches of DNA — allowing them to look at how specific areas of chromosomes interact physically in more detail than ever before. Previous techniques used to investigate long-range DNA interactions were not sensitive enough to produce definitive results.

The researchers assessed 14 regions of DNA that contain single-letter variations previously linked to bowel cancer risk. They detected significant long-range interactions for all 14 regions, confirming their role in gene regulation. These interactions are important because they can control how genes behave, and alterations in gene behaviour can lead to cancer — in fact most genetic variations that have been linked to cancer risk are not in genes themselves, but in the areas of the genome that regulate them.

Study leader Professor Richard Houlston, Professor of Molecular and Population Genetics at The Institute of Cancer Research, London, said: “Our new technique shows that genetic variations are able to increase cancer risk through long-range looping interactions with cancer-causing genes elsewhere in the genome. It is sometimes described as analogous to a wormhole, where distortions in space and time could in theory bring together distant parts of the universe. Understanding how long-range genetic regulation works is crucial to understanding how cancer develops — and could be important in finding new ways to treat the disease in the future.”

Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said: “A lot of the genetic variants already linked to cancer occur in gene deserts — often very long and quite mysterious DNA sequences that don’t actually contain ‘genes’, but which are involved in causing cancer in ways we do not yet fully understand.

“DNA looping is notoriously difficult to study but this research has taken an important step to understanding what genetic variations in DNA deserts might do to drive the development of bowel cancer.”

I’m Dr. Michael Hunter.


Story Source:

The above story is based on materials provided by Institute of Cancer Research. Note: Materials may be edited for content and length.


Journal Reference:

  1. Roland Jäger, Gabriele Migliorini, Marc Henrion, Radhika Kandaswamy, Helen E. Speedy, Andreas Heindl, Nicola Whiffin, Maria J. Carnicer, Laura Broome, Nicola Dryden, Takashi Nagano, Stefan Schoenfelder, Martin Enge, Yinyin Yuan, Jussi Taipale, Peter Fraser, Olivia Fletcher, Richard S. Houlston. Capture Hi-C identifies the chromatin interactome of colorectal cancer risk loci. Nature Communications, 2015; 6: 6178 DOI: 10.1038/ncomms7178

Cite This Page:

Institute of Cancer Research. “Cancer risk linked to DNA ‘wormholes’.” ScienceDaily. ScienceDaily, 19 February 2015. <www.sciencedaily.com/releases/2015/02/150219090349.htm>.

How Can You Reduce Your Risk of Getting Cancer?

Recent reports suggest that about 2 out of 3 cancers may be due to “bad luck.” Today, we focus on the other third: What can you do to reduce your risk of cancer?

What You Need to Know:

  • Maintaining a healthy body weight and being physically active had the greatest impact on overall risk of a cancer-related death. 
  • Restricting alcohol consumption to one drink per day for women and two drinks per day for men was associated with 29% reduced risk for obesity-related cancers. Additionally, the risk was up to 71% lower for the most common site-specific cancers in the United States (breast, prostate, and colorectal).

Background

  • As people make their resolutions for 2015, two new studies — which show that curbing alcohol consumption, adding more plant foods to the diet, and losing excess weight can help reduce the risk of developing cancer — serve as a reminder that a healthy lifestyle is important.
  • In 1997, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued cancer prevention guidelines for weight management, diet, and physical activity. These were updated in 2007 and are considered to be the most comprehensive scientific analysis of cancer prevention and causation ever undertaken. Specifically, the guidelines reported that excess body fat is associated with an increased cancer risk and that there is convincing evidence that the consumption of alcohol, red meat, and processed meat elevates cancer risk. Since that time, numerous studies have reported links between colorectal cancer risk and alcohol, between breast cancer mortality and obesity, between breast cancer relapse and obesity, and between breast cancer risk and red meat.

The Evidence: The first study, published online January 6 in Cancer Causes & Control, showed that eating a plant-based diet and limiting alcohol intake, both already included in various cancer prevention guidelines, could help cut the risk for obesity-related cancers (about a third of all of cancers). In a cohort of nearly 3000 adults, the researchers found that restricting alcohol consumption to one drink per day for women and two drinks per day for men was associated with 29% reduced risk for obesity-related cancers. Additionally, the risk was up to 71% lower for the most common site-specific cancers in the United States (breast, prostate, and colorectal). For individuals who consume starchy vegetables, such as corn, potatoes, and yams, sufficient consumption of nonstarchy legumes, fruits, and vegetables was associated with a reduction in the risk for colorectal cancer.

Pronounced Effect on Cancer Risk

In their study, Makarem and colleagues investigated whether the healthful behaviors outlined in the WCRF/AICR guidelines were associated with the risk for obesity-related cancers, in particular, breast, prostate, and colorectal cancer. Of the 2983 adults enrolled in the Framingham Offspring cohort from 1991 to 2008, the researchers identified 480 incident obesity-related cancers.

Data from food frequency questionnaires, anthropometric measures, and self-reported physical activity were used to develop a 7-component score based on recommendations for body fatness; physical activity; foods that promote weight gain; plant foods; animal foods; alcohol; and food preservation, processing, and preparation. The cohort was, on average, middle aged to older and overweight, but had a relatively high level of physical activity. The mean duration of follow-up was 11.5 years.

The overall score was not associated with obesity-related cancer risk after adjustment for confounders such as age, sex, smoking, energy, and pre-existing conditions (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.86 – 1.02). However, when the score components were considered separately, the researchers found that for every unit increment in the alcohol score (representing an improvement and more closely meeting the guideline recommendations), there was 29% lower risk for obesity-related cancers (HR, 0.71; 95 % CI, 0.51 – 0.99) and a 49% to 71% reduced risk for breast, prostate, and colorectal cancers.

Similarly, each unit increment in the subcomponent score for nonstarchy plant foods (fruits, vegetables, and legumes) for those who eat starchy vegetables was associated with a 66% lower risk for colorectal cancer (HR, 0.44; 95% CI, 0.22 – 0.88).

Healthy Body Weight and Exercise Reduce Mortality

The second study, published online January 7 in the American Journal of Clinical Nutrition, reported similar results. Researchers found that greater adherence to the cancer prevention guidelines of the American Cancer Society (ACS) was associated with a reduction not only in cancer incidence, but also in cancer mortality and total mortality.

The ACS guidelines recommend that individuals avoid smoking, achieve and maintain a healthy weight, be physically active, and eat a healthy diet that emphasizes plant foods. In their study, Geoffrey Kabat, PhD, senior epidemiologist in the Department of Epidemiology & Population Health at the Albert Einstein College of Medicine in Bronx, New York, and colleagues report that maintaining a healthy body weight and being physically active had the greatest impact on overall mortality for both men and women.

The researchers used data from the NIH-AARP Diet and Health Study, a prospective cohort study of 566,401 adults who were 50 to 71 years of age in 1995 and 1996, when they enrolled in the study. They were followed for a median of 10.5 years for cancer incidence, 12.6 years for cancer mortality, and 13.6 years for total mortality.

During the study period, there were 73,784 cases of cancer, 16,193 cancer deaths, and 81,433 deaths from any cause. The patients were stratified by how closely they adhered to ACS guidelines, and adherence to the guidelines was associated with a reduced risk for all cancers combined. When the highest level of adherence was compared with the lowest level, the hazard ratio was 0.90 for men and 0.81 for women.

In addition, increased adherence was associated with a reduction in risk for 14 of 25 specific cancers. Reduction in the risk for gallbladder cancer was 65% in men and women combined, for endometrial cancer was 60%, for liver cancer was 48% in men, for colon cancer was 48% in men and 35% in women, and for rectal cancer was 40% in men and 36% in women.

My Take: These results add to the existing evidence on the potential role of limiting alcohol intake and increasing the intake of plant foods in influencing cancer risk. Dietary advice on cancer should focus on encouraging the consumption of a plant-based diet providing abundant non-starchy fruits, vegetables, and legumes, and restricting alcohol, if consumed at all, to the recommended levels. Try to stick to the ACS Guidelines, as the closer you follow them, the greater the benefit in cancer risk-reduction. Finally, exercise and don’t use tobacco. I’m Dr. Michael Hunter.

References: Cancer Causes Control. Published online January 6, 2015. Abstract; Am J Clin Nutr. Published online January 7, 2015. Abstract; http://www.medscape.com/viewarticle/837976#vp_2

Can African-American Women Reduce Their Breast Cancer Risk?

What You Need to Know: High levels of vigorous exercise or brisk walking may be associated with a reduction in incidence of breast cancer in African American women.

Background: Physical activity has been associated with reduced risk of breast cancer. However, evidence on the association in African Americans has been limited.

The Study: Using prospective data from the Black Women’s Health Study, researchers assessed vigorous exercise and walking in relation to incidence of invasive breast cancer overall (n=1,364), estrogen receptor–positive (ER+, n=688) cancer, and estrogen receptor–negative (ER–, n=405) cancer, based on 307,672 person years of follow–up of 44,708 African American women aged 30 or older at enrollment.

Results: This prospective study found that high levels of vigorous exercise or brisk walking may be associated with a reduction in incidence of breast cancer in African American women.

  • Vigorous exercise at baseline was inversely associated with overall breast cancer incidence (p trend=0.05): the IRR for ≥ 7 hour/week relative to < 1 hour/week was 0.74 (95% CI 0.57–0.96).
  • The association did not differ by ER status.
  • Brisk walking for ≥ 7 hours/week was associated with a reduction similar to that for vigorous exercise.
  • Vigorous exercise at age 30, age 21, or in high school was not associated with breast cancer incidence.
    Sitting for long periods at work or watching TV was not significantly associated with breast cancer incidence.

My Take: You can reduce your risk of breast cancer by about a quarter by simply walking briskly on a regular basis. Aim for an hour a day. Now, go do it! I’m Dr. Michael Hunter.

The small print: The material presented herein is informational only, and is not designed to provide specific guidance for an individual. Please check with a valued health care provider with any questions or concerns. As for me, I am a Harvard- , Yale- and UPenn-educated radiation oncologist, and I practice in the Seattle, WA (USA) area. I feel genuinely privileged to be able to share with you. If you enjoyed today’s offering, please consider clicking the follow button at the bottom of this page.

Available now: Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Both can be found at the Apple Ibooks store. Coming Soon for iPad: Understand Breast Cancer in 60 Minutes; Understand Colon Cancer in 60 Minute; Understand Colon Cancer in 60 Minutes; Understand Brain Glioma in 60 Minutes. Thank you.

Reference: Rosenberg et al. Cancer Epidemiology, Biomarkers & Prevention. Cancer Epidemiol Biomarkers Prev. 2014 Aug 7. [Epub ahead of print]