Intake of Meat Mutagens and Risk of Prostate Cancer in a Cohort of U.S. Health Professionals

Abstract

Background Evidence relating heterocyclic aromatic amines (HCA), associated with high-temperature cooking methods, to prostate cancer risk is inconsistent Methods In a large US cohort study, intakes of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and a meat-derived mutagenicity index (MDM) were assessed using a cooking method questionnaire administered in 1996. Until 2010, 2,770 prostate cancer cases were observed among 26,030 participants. Results Intake of PhIP from red meat was statistically significantly associated with total prostate cancer risk (top vs. bottom quintile HR=1.18, 95% CI 1.03–1.35), but not other HCAs (MeIQx, 1.12, 0.98–1.27, PhIP from white meat, 1.08, 0.95–1.22, DiMeIQx, 1.09, 0.97–1.21) or MDM (1.13, 1.00–1.28). For high grade (Gleason sum 7 with pattern 4+3 and Gleason sum 8–10, n=483 cases) and advanced cancers (n=281), we only observed positive associations for PhIP from red meat (top vs. bottom quintile: high grade: HR=1.44, 95% CI 1.04–1.98, p-trend=0.03; advanced: HR=1.50, 95% 0.99–2.26; p-trend=0.12), but associations for advanced cancers did not reach statistical significance. Observed associations remained similar after adjustment for total, unprocessed or processed red meat intake. Conclusion Observed positive associations between PhIP intake from red meat and prostate cancer, particularly high-grade and possibly also advanced prostate cancer need to be confirmed in other studies. Impact Results do not provide strong evidence that HCAs increase risk of prostate cancers.

A review and meta-analysis of prospective studies of red and processed meat, meat cooking methods, heme iron, heterocyclic amines and prostate cancer

“…Characteristics of prospective cohort studies of various meat cooking methods, heterocyclic amines, heme iron intake and prostate cancer are shown in Table 3 [ 16 , 18 , 34 , 44 , 47 , 49 , 50 ]. The results for these meta-analyses are shown in Table 4 .…”

“…of subjects (No. of cases) Age range (mean) Year baseline diet assessed Follow-up, years Meat cooking methods exposures analyzed Heterocyclic amine or heme iron exposures analyzed Prostate cancer outcome Cross et al, 2005 [ 47 ] PLCO (US) 29,361 (1338) 55–74 1993–2001 11 Barbequed meat; panfried meat; very well-done meat DiMeIQx; MeIQx; PhIP; B(a)P; Mutagenic activity Total PCa; incident PCa; advanced PCa Jackszyn 2012 [ 50 ] EPIC (Europe) 139,005 (4606) >30 1989–2004 11 None Heme iron Total PCa, advanced PCa, localized PCa Koutros et al, 2008 [ 34 ] AHS (US) 23,080 (668) 48.3 [mean] 1993–1997 10 Grilled meat; pan-fried meat; broiled meat; rare or medium cooked meat; well and very well done cooked meat DiMeIQx; MeIQx; PhIP; B(a)P; Mutagenic activity Total PCa; incident PCa; advanced PCa Rohrmann et al, 2015 [ 49 ] HPFS (US) 26,030 (2770) 40–75 1996 14 None MeIQx; DiMeIQx; PhIP; Meat-Derived Mutagenicity Index Total PCa, advanced or lethal PCa Sander et al, 2011 [ 16 ] EPIC-Heidelberg (Germany) 9578 (337) 40–65 2002–2004 7 Degree of browning: strong/extreme; light/moderate DiMeIQx; MeIQx; PhIP Total PCa; advanced PCa Sharma et al, 2010 [ 18 ] Multiethnic Cohort (US) 4169 (2106) 45–75 1993–1996 8 Meat preference: medium; well done None Total PCa Sinha et al, 2009 [ 44 ] NIH-AARP (US) 175,343 (10,313) 50–71 ...…”

“…The prospective cohort studies that provided results for cooking methods and total and advanced prostate cancer also provided estimates for various heterocyclic amines [ 16 , 18 , 34 , 44 , 47 ]. Additionally, Rohrmann et al recently published an update of HCA consumption and prostate cancer in the Health Professionals Follow-Up Study (HPFS) cohort [ 49 ]. The heterocyclic amines evaluated included B(a)P, DiMeIQx, MeIQx, PhIP, and total mutagenic activity.…”

“…We did not observe any increased risk specifically for advanced or lethal prostate cancer with consumption of total red meat, fresh red meat, or processed meat, or any cooking method, HCA, or heme iron. Some of the cohort studies included in our meta-analysis provided results by prostate cancer grade (high/low) [ 39 , 49 , 50 ]. However, these data were too sparse and heterogeneous to combine analytically.…”

Purple rice extract inhibits testosterone‐induced rat prostatic hyperplasia and growth of human prostate cancer cell line by reduction of androgen receptor activation

“…In this study, the purple rice extracts not only showed a strongly anti‐mutagenic effect against mutagenesis of selected carcinogens, including PhIp, Glu‐P‐1, and IQ in a dose‐dependent manner, but the purple rice extracts up to 500 µg/plate also did not cause mutagenicity in S. typhimurium strains TA98 and TA100, either with or without the S9 mixture, when compared with the standard mutagens. Although little is known about the relationship between these mutagens and prostate cancer, it has recently been reported that the consumption of PhIP from processed red meat is associated with a higher prostate cancer risk (Rohrmann et al, ). PhIP is a major carcinogen that is generated from cooking meats at high temperatures (Felton et al, ), which causes the formation of DNA adducts that lead to carcinogenesis (Tang et al, ).…”