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[UK] Meat and Breast Cancer

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    http://www.sciencenews.org/articles/20071020/food.asp Science News - Oct. 20, 2007 By Janet Raloff Women take note. Researchers find that a chemical that forms
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      Science News - Oct. 20, 2007
      By Janet Raloff

      Women take note. Researchers find that a chemical that forms in
      overcooked meat, especially charred portions, is a potent mimic of
      estrogen, the primary female sex hormone. That's anything but
      appetizing, since studies have linked a higher lifetime cumulative
      exposure to estrogen in women with an elevated risk of breast cancer.

      Indeed, the new finding offers a "biologically plausible" explanation
      for why diets rich in red meats might elevate breast-cancer risk,
      notes Nigel J. Gooderham of Imperial College London.

      At the very high temperatures reached during frying and charbroiling,
      natural constituents of meats can undergo chemical reactions that
      generate carcinogens known as heterocyclic amines (see Carcinogens in
      the Diet http://www.sciencenews.org/articles/20050219/food.asp).
      Because these compounds all have very long, unwieldy
      chemical monikers, most scientists refer to them by their
      abbreviations, such as IQ, MeIQ, MeIQx, and PhIP.

      Of the nearly two dozen different heterocyclic amines that can form,
      PhIP dominates. It sometimes accumulates in amounts 10 to 50 times
      higher than that of any other member of this toxic chemical family,
      Gooderham says. Moreover, he adds, although heterocyclic amines
      normally cause liver tumors in exposed animals, PhIP is different: "It
      causes breast cancer in female rats, prostate cancer in male rats, and
      colon cancer in both." These are the same cancers that in people are
      associated with eating a lot of cooked meats.

      However, the means by which such foods might induce cancer has
      remained somewhat elusive. So, building on his team's earlier work,
      Gooderham decided to probe what the heterocyclic amine did in rat
      pituitary cells. These cells make prolactin -- another female sex
      hormone -- but only when triggered by the presence of estrogen.
      Prolactin, like estrogen, fuels the growth of many breast cancers.

      In their new test-tube study, Gooderham and coauthor Saundra N. Lauber
      show that upon exposure to PhIP, pituitary cells not only make
      progesterone, but also secrete it. If these cells do the same thing
      when they're part of the body, those secretions would circulate to
      other organs -- including the breast.

      But "what was startling," Gooderham told Science News Online, is that
      it took just trace quantities of the heterocyclic amine to spur
      prolactin production. "PhIP was incredibly potent," he says, able to
      trigger progesterone production at concentrations comparable to what
      might be found circulating in the blood of people who had eaten a
      couple of well-done burgers.

      The toxicologist cautions that there's a big gap between observing an
      effect in isolated cells growing in a test-tube and showing that the
      same holds true in people.

      However, even if PhIP does operate similarly in people, he says that's
      no reason to give up grilled meat. Certain cooking techniques, such as
      flipping hamburgers frequently, can limit the formation of
      heterocyclic amines. Moreover, earlier work by the Imperial College
      team showed that dining on certain members of the mustard family
      appear to detoxify much of the PhIP that might have inadvertently been
      consumed as part of a meal.

      The human link

      Three recent epidemiological studies support concerns about the
      consumption of grilled meats.

      In the first, Harvard Medical School researchers compared the diets of
      more than 90,000 premenopausal U.S. nurses. Over a 12-year period,
      1,021 of the relatively young women developed invasive breast cancers.
      The more red meat a woman ate, the higher was her risk of developing
      invasive breast cancer, Eunyoung Cho and her colleagues reported in
      the Archives of Internal Medicine last November. The increased risk
      was restricted, however, only to those types of breast cancers that
      are fueled by estrogen or progesterone.

      Overall, women who ate the most red meat -- typically 1.5 servings or
      more per day -- faced nearly double the invasive breast-cancer risk of
      those eating little red meat each week.

      Related findings emerged in the April 10 British Journal of Cancer.
      There, researchers at the University of Leeds reported data from a
      long-running study of more than 35,000 women in the United Kingdom who
      ranged in age from roughly 35 to 70. Regardless of the volunteers'
      age, Janet E. Cade's team found, those who consumed the most meat had
      the highest risk of breast cancer.

      Shortly thereafter, Susan E. Steck of the University of South
      Carolina's school of public health and her colleagues linked meat
      consumption yet again with increased cancer risk, but only in the
      older segment of the women they investigated. By comparing the diets
      of 1,500 women with breast cancer to those of 1,550 cancerfree women,
      the scientists showed that postmenopausal women consuming the most
      grilled, barbecued, and smoked meats faced the highest breast-cancer

      These data support accumulating evidence that a penchant for well-done
      meats can hike a woman's breast-cancer risk, Steck and her colleagues
      concluded in the May Epidemiology.

      PhIP fighters

      Such findings have been percolating out of the epidemiology community
      for years. Nearly a decade ago, for instance, National Cancer
      Institute scientists reported finding that women who consistently ate
      their meat very well done -- with a crispy, blackened crust -- faced a
      substantially elevated breast-cancer risk when compared to those who
      routinely ate rare- or medium-cooked meats.

      However, even well-done meats without char can contain heterocyclic
      amines, chemical analyses by others later showed. The compounds'
      presence appears to correlate best with how meat is cooked, not merely
      with how brown its interior ended up (SN: 11/28/98, p. 341).

      At high temperatures, the simple sugar glucose, together with
      creatinine -- a muscle-breakdown product, and additional free amino
      acids, can all interact within beef, chicken, and other meats to form
      heterocyclic amines. In contrast, low-temperature cooking or a quick
      searing may generate none of the carcinogens.

      Because there's no way to tell visually, by taste, or by smell whether
      PhIP and its toxic kin lace cooked meat, food chemists have been
      lobbying commercial and home chefs to reduce the heat they use to cook
      meats -- or to turn meats frequently to keep the surfaces closest to
      the heat source from getting too hot.

      The significance of this was driven home to Gooderham several years
      ago when just such tactics spoiled an experiment he was launching to
      test whether Brussels sprouts and broccoli could help detoxify PhIP.
      "I bought 30 kilograms of prime Aberdeen angus lean beef," he recalls.
      "Then we ground it up and I gave it to a professional cook to turn
      into burgers and cook." Professional cooks tend to move meats around
      quite a bit, he found. The result: His expensive, chef-prepared meat
      contained almost no PhIP.

      In the end, he says, "I sacked the cook, bought another 30 kilos of
      meat and prepared the burgers myself. It was a costly lesson."

      Once restarted, however, that study yielded encouraging data.

      One way the body detoxifies and sheds toxic chemicals is to link them
      to what amounts to a sugar molecule. Consumption of certain members of
      the mustard (Brassica) family, such as broccoli and Brussels sprouts
      (both members of the B. oleracea species) -- can encourage this
      process. So Gooderham's team fed 250 grams (roughly half a pound) each
      of broccoli and Brussels sprouts each day to 20 men for almost 2
      weeks. On the 12th day, the men each got a cooked-meat meal containing
      4.9 micrograms of PhIP.

      Compared to similar trial periods when their diets had been Brassica-
      free, the volunteers excreted up to 40 percent more PhIP in urine, the
      researchers reported in Carcinogenesis.

      Experimental data suggest that two brews may also help detoxify
      heterocyclic amines. In test-tube studies, white tea largely prevented
      DNA damage from the heterocyclic amine IQ (SN: 4/15/00, p. 251), and
      in mice, extracts of beer tackled MeIQx and Trp-P-2 (see Beer's Well
      Done Benefit http://www.sciencenews.org/articles/20050305/food.asp).

      The best strategy of all, most toxicologists say, is to prevent
      formation of heterocyclic amines in the first place. In addition to
      frequently turning meat on the grill or fry pan, partially cooking
      meats in a microwave prior to grilling will limit the toxic chemicals'
      formation. So will mixing in a little potato starch to ground beef
      before grilling (see How Carbs Can Make Burgers Safer http://www.sciencenews.org/articles/20041204/food.asp) or
      marinating meats with a heavily sugared oil-and-vinegar sauce (SN: 4/24/99, p.


      Cho, E., et al. 2006. Red meat intake and risk of breast cancer among
      premenopausal women. Archives of Internal Medicine 166(Nov.
      13):2253-2259. Abstract available at http://archinte.ama-as
      <BLOCKED::http://archinte.ama-assn.org/cgi/content/short/166/20/2253> .

      Felton, J.S., et al. 1995. Reduction of heterocyclic aromatic amine
      mutagens/carcinogens in fried beef patties by microwave pretreatment.
      Available at http://www.llnl.gov/str/pdfs/UCRL-JC-116450.pdf
      <BLOCKED::http://www.llnl.gov/str/pdfs/UCRL-JC-116450.pdf> .

      Gooderham, N.J., et al. 2007. Mechanisms of action of the carcinogenic
      heterocyclic amine PhIP. Toxicology Letters 168(Feb. 5):269-277.
      Abstract available at http://dx.doi.org/10.1016/j.toxlet.20
      06.10.022 <BLOCKED::http://dx.doi.org/10.1016/j.toxlet.2006.10.022> .

      Lauber, S.N., and N.J. Gooderham. 2007. The cooked meat-derived
      genotoxic carcinogen 2-amino-3-methylimidazo[4,5-b]pyridine has potent
      hormone-like activity: Mechanistic support for a role in breast
      cancer. Cancer Research 67(Oct. 1):9597-9602. Abstract available at

      Murray, S.,... and N.J. Gooderham. 2001. Effect of cruciferous
      vegetable consumption on heterocyclic aromatic amine metabolism in
      man. Carcinogenesis 22(September):1413-1420. Available at http:/

      Steck, S.E., et al. 2007. Cooked meat and risk of breast cancer --
      Lifetime versus recent dietary intake. Epidemiology 18(May):373-382.
      Abstract available at

      Taylor, E.F., et al. 2007. Meat consumption and risk of breast cancer
      in the UK Women's Cohort Study. British Journal of Cancer 96(April
      10):1139-1146. Available at

      Walters, D.G.... N.J. Gooderham, et al. 2004. Cruciferous vegetable
      consumption alters the metabolism of the dietary carcinogen 2-amino-1-
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans. Carcinogenesis
      25(September):1659-1669. Available at

      Further Readings:

      Raloff, J. 2007. Concerns over genistein, part II -- Beyond the heart.
      Science News Online (July 7). Available at http://www.scie
      <BLOCKED::http://www.sciencenews.org/articles/20070707/food.asp> .

      ______. 2007. Concerns over genistein, part I -- The heart of the
      issue. Science News Online (June 16). Available at
      http://www.sciencene ws.org/articles/20070616/food.asp
      <BLOCKED::http://www.sciencenews.org/articles/20070616/food.asp> .

      ______. 2006. Pesticides mimic estrogen in shellfish. Science News
      170(Dec. 16):397. Available to subscribers at http://www.scien
      <BLOCKED::http://www.sciencenews.org/articles/20061216/note12.asp> .

      ______. 2006. No-stick chemicals can mimic estrogen. Science News
      170(Dec. 2):366. Available to subscribers at http://www.scie
      <BLOCKED::http://www.sciencenews.org/articles/20061202/note16.asp> .

      ______. 2006. Meat poses exaggerated cancer risk for some people.
      Science News Online (March 25). Available at http://www.scien
      <BLOCKED::http://www.sciencenews.org/articles/20060325/food.asp> .

      ______. 2005. Beer's well done benefit. Science News Online (March 5).
      Available at http://www.sciencenews.org/articles/20050305/food.asp
      <BLOCKED::http://www.sciencenews.org/articles/20050305/food.asp> .

      ______. 2005. Carcinogens in the diet. Science News Online (Feb. 19).
      Available at http://www.sciencenews.org/articles/20050219/food.asp
      <BLOCKED::http://www.sciencenews.org/articles/20050219/food.asp> .

      ______. 2004. How carbs can make burgers safer. Science News Online
      (Dec. 4). Available at http://www.sciencenews.org/articles/20041
      <BLOCKED::http://www.sciencenews.org/articles/20041204/food.asp> .

      ______. 2004. Uranium, the newest 'hormone'. Science News 166(Nov.
      13):318. Available to subscribers at http://www.sciencenews.or
      <BLOCKED::http://www.sciencenews.org/articles/20041113/note14.asp> .

      ______. 2001. Fire retardant catfish? Science News Online (Dec. 8).
      Available at http://www.sciencenews.org/articles/20011208/food.asp
      <BLOCKED::http://www.sciencenews.org/articles/20011208/food.asp> .

      ______. 1999. Well-done research. Science News 155(April 24):264-266.
      Available at http://www.sciencenews.org/pages/sn_arc99/4_24_99/b
      <BLOCKED::http://www.sciencenews.org/pages/sn_arc99/4_24_99/bob1.htm> .

      ______. 1998. Very hot grills may inflame cancer risks. Science News
      154(Nov. 28):341. Available at http://www.sciencenews.org/pages/s
      <BLOCKED::http://www.sciencenews.org/pages/sn_arc98/11_28_98/fob3.htm> .

      ______. 1996. Another meaty link to cancer. Science News 149(June
      8):365. Available at http://www.sciencenews.org/pages/pdfs/da
      f> .

      ______. 1996. 'Estrogen' pairings can increase potency. Science News
      149(June 8):356. Available at http://www.sciencenews.org/pages/
      f> .

      ______. 1995. Beyond estrogens: Why unmasking hormone-mimicking
      pollutants proves so challenging. Science News 148(July 15):44.
      Available at http://www.sciencenews.org/pages/pdfs/data/1
      f> .

      ______. 1994. Meaty carcinogens: A risk to the cook? Science News
      146(Aug. 13):103.

      ______. 1994. Not so hot hot dogs? Science News 145(April 23):264-269.

      ______. 1994. How cooked meat may inflame the heart. Science News
      145(March 12):165.

      ______. 1994. The gender benders. Science News 145(Jan. 8):24.
      Available at http://www.sciencenews.org/pages/sn_edpik/ls_7.htm
      <BLOCKED::http://www.sciencenews.org/pages/sn_edpik/ls_7.htm> .

      Smith-Roe, S.L., et al. 2006. Induction of aberrant crypt foci in DNA
      mismatch repair-deficient mice by the food-borne carcinogen 2-amino-1-
      methyl-6-phenylimidazo [4,5-b] pyridine (PhIP). Cancer Letters.
      244(Nov. 28):79-85. Abstract available at http://dx.doi.org/10.101
      <BLOCKED::http://dx.doi.org/10.1016/j.canlet.2005.12.002> .

      ______. 2006. Mlh1-dependent responses to 2-amino-1-methyl-6-
      phenylimidazo [4,5-b] pyridine (PhIP), a food-borne carcinogen.
      (Abstract # 514). Toxicologist 90(March):105.

      ______. 2006. Mlh1-dependent suppression of specific mutations induced
      in vivo by the food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo
      [4,5-b] pyridine (PhIP). Mutation Research/Fundamental and Molecular
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      <BLOCKED::http://dx.doi.org/10.1016/j.mrfmmm.2005.08.011> .


      Janet E. Cade
      UK Women's Cohort Study Centre for Epidemiology and Biostatistics
      30/32 Hyde Terrace
      The University of Leeds
      Leeds LS2 9LN
      United Kingdom

      Eunyoung Cho
      Channing Laboratory
      Department of Medicine
      Harvard Medical School
      181 Longwood Avenue
      Boston, MA 02115

      Nigel J. Gooderham
      Biomolecular Medicine
      Imperial College London
      Sir Alexander Fleming Building
      London SW7 2AZ
      United Kingdom

      Susan Elizabeth Steck
      Department of Epidemiology and Biostatistics
      Statewide Cancer Prevention and Control Program
      Arnold School of Public Health
      University of South Carolina
      2221 Devine Street, Room 231
      Columbia, SC 29208

      Copyright 2007 Science Service

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