Academic journal article Environmental Health Perspectives

A Prospective Analysis of Meat Mutagens and Colorectal Cancer in the Nurses' Health Study and Health Professionals Follow-Up Study

Academic journal article Environmental Health Perspectives

A Prospective Analysis of Meat Mutagens and Colorectal Cancer in the Nurses' Health Study and Health Professionals Follow-Up Study

Article excerpt


Cooking meat at high temperature and for a long duration produces several mutagenic compounds such as heterocyclic amines (HCAs). In the human diet, major HCAs include 2-Amino-3,8-dimethylimidazo(4,5-j) quinoxaline (MeIQx), 2-amino-1-methyl6-phenylimidazo(4,5-b) pyridine (PhIP), and 2-amino-3,4,8-trimethylimidazo(4,5-f) quinoxaline (DiMeIQx). Animal studies have provided sufficient evidence for their carcinogenic potential [Group 2B, International Agency for Research on Cancer (IARC)] of MeIQx, DiMeIQx, and PhIP (IARC 1993; NTP 2014); however, in humans, epidemiological data relating HCA intake to risk of colorectal cancer (CRC) are inconsistent (Augustsson et al. 1999; Butler et al. 2003; Cross et al. 2010; Gilsing et al. 2012; Helmus et al. 2013; Kobayashi et al. 2009; Le Marchand et al. 2002; Miller et al. 2013; Nothlings et al. 2009; Nowell et al. 2002; Ollberding et al. 2012; Joshi et al. 2015). Given the paucity of prospective data relating HCA intake to CRC, we used data from the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) to investigate the association between meat mutagen intake and risk of CRC. The long follow-up (14 years) and large number of cases also allowed us to assess associations by subsites and to conduct lagged analyses with sufficient statistical power. Our specific hypotheses were that a) higher intake of meat mutagens would be associated with higher risk of CRC, and b) associations between meat mutagens and CRC would vary by cancer sub-sites and by latency period between exposure and disease.


Study Population

We used data from two large prospective cohort studies: the HPFS, which included 51,529 U.S. male health professionals, 40-75 years of age at enrollment in 1986; and the NHS, which included 121,700 U.S. female nurses, 30-55 years of age at enrollment in 1976. More details on the cohorts and data collection can be found elsewhere (Colditz et al. 1997; Rimm et al. 1991). In brief, at baseline and then every 2 years thereafter, participants in both cohorts received questionnaires inquiring about medical history and lifestyle. The study protocol was approved by the Human Subjects Committee of the Brigham and Women's Hospital and the Harvard T.H. Chan School of Public Health. Completion and return of the questionnaires was considered implied consent.

Assessment of Diet

Dietary information was obtained from validated semi-quantitative food frequency questionnaires (FFQ) (Feskanich et al. 1993; Rimm et al. 1992; Salvini et al. 1989; Willett et al. 1985). In the HPFS, a 131-item FFQ was administered at the time the cohort was established in 1986, follow-up FFQs were mailed every 4 years (e.g., 1990, 1994, 1998). In the NHS, FFQs were administered in 1984, 1986 and then every 4 years thereafter (e.g., 1990, 1994, 1998). Because the cooking questionnaire was administered during a non-FFQ follow-up questionnaire cycle in 1996 (start of follow-up for this current study), intake of nutrients such as calcium or folate or foods such as total red meat was estimated using data from our FFQs. On each FFQ, participants were asked how often on average they ate a specific food item (using a specified portion size) during the past year. Participants were given nine categories of frequency of intake to choose from: never or < 1/month, 1-3/month, 1/week, 2-4/week, 5-6/week, 1/day, 2-3/day, 4-5/day and [greater than or equal to] 6/day. We computed nutrient intake by multiplying the nutrient content of foods with the reported frequency of intake of each food from the FFQs and applied the residual method to calculate energy-adjusted nutrient intakes (Willett 2013a). Cumulative updated nutrient and diet intake was computed by averaging the intakes from all available FFQs up to the most recent 2-year follow-up cycle. We used cumulative intake to enhance our estimate of long-term dietary intake (Willett 2013b).

Assessment of HCA Intake

To better estimate HCA intake in our cohorts, we previously conducted a pilot study (Byrne et al. …

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