RISK OF ADENOCARCINOMA OF THE STOMACH AND ESOPHAGUS WITH MEAT COOKING METHOD AND DONENESS PREFERENCE Mary H. WARD, 1 * Rashmi SINHA, 1 Ellen F. HEINEMAN, 1 Nathaniel ROTHMAN, 1 Rodney MARKIN, 2 Dennis D. WEISENBURGER, 2 Pelayo CORREA 3 and Shelia Hoar ZAHM 1 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 2 Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 3 Department of Pathology, Louisiana State University, New Orleans, LA Meatscooked at high temperatures(frying, grilling) and for a long duration contain heterocyclic amines (HCAs), which are both mutagens and animal carcinogens. Additionally, barbecuing/grilling of meats produces polycyclic aromatic hydrocarbons (PAHs). Consumption of well-done meat has been associated with an increased risk of colon cancer but has not been evaluated as a risk factor for stomach or esophageal cancers. W e conducted a population-based case-control study in 66 counties of eastern Nebraska. Telephone interviews were conducted with white men and women diagnosed with adenocarcinoma of the stomach (n 5 176) and esophagus (n 5 143) between July 1988 and June 1993 and 502 controls. T he dietary assessment included several questions about usual cooking methods for meats and doneness preference for beef. H igh intake of red meat was associated with increased risks for both stomach and esophageal cancers. Overall, broiling or frying of beef, chicken or pork was not associated with the risk of these tumors. Barbecuing/grilling, reported as the usual cooking method for a small number of study participants, was associated with an elevated risk of stomach and esophageal cancers. After excluding those who reported usually barbecuing/grilling, a source of both PAHs and HCAs, we evaluated doneness level as a surrogate for HCA exposure. Compared to a preference for rare/medium rare beef, odds ratios were 2.4 for medium, 2.4 for medium well and 3.2 for well done, a significant positive trend. Doneness level was not associated with a significant trend in risk of esophageal cancer. Int. J. Cancer, 71:14–19, 1997. r 1997 Wiley-Liss, Inc. ² Dietary risk factors for stomach and esophageal cancers have been evaluated extensively. Low intake of fruits and vegetables increases the risk of stomach and esophageal cancers (Graham et al., 1990; Steinmetz and Potter, 1991; Correa et al., 1985; Risch et al., 1985; Buiatti et al., 1989; Tavani et al., 1994; Ziegler et al., 1981). An increased risk of stomach cancer has also been associ- ated with high intake of salt and processed meats containing nitrite (Graham et al., 1990; Risch et al., 1985; Buiatti et al., 1989, 1990). Consumption of fried or broiled meats has been investigated as a risk factor for stomach cancer, but results have been equivocal (Kato et al., 1992; Steineck et al., 1993; Knekt et al., 1994; IARC, 1993; Jedrychowski et al., 1992). A few studies of stomach and esophageal cancers have shown elevated risks with high intake of smoked or barbecued meats (Correa et al., 1985; Wu-Williams et al., 1990; Risch et al., 1985; Castelletto et al., 1994). Consumption of ‘‘well-done’’ or ‘‘well-browned’’ meat has been associated with an increased risk of colorectal cancers (Schiffman and Felton, 1990; Lang et al., 1994; Gerhardsson de Verdier et al., 1991) but has not been evaluated for stomach or esophageal cancers. Cooking methods are of interest because frying and grilling/barbecuing (cooking over an open flame, charcoal or ceramic briquets) are high-temperature cooking methods which can produce high levels of heterocyclic amines (HCAs) and other pyrolysis products compared to low or negligible levels found with boiling, baking or roasting (Adamson, 1990; Layton et al., 1995; Sinha et al., 1995). Grilling/barbecuing of meats also produces polycyclic aromatic hydrocarbons (PAHs), which form when fat drips onto the flame or heat surface, pyrolyses and comes up in smoke, which coats the surface of the meat. HCAs increase with increasing duration of cooking or ‘‘doneness’’of the meat (Sinha et al., 1995; Knize et al., 1996). Oral administration of HCAs and PAHs has produced gastro-intestinal tract tumors in animal studies (Adamson, 1990; Wattenberg et al., 1979). We conducted a population-based case-control study of adenocar- cinoma of the stomach and esophagus in Nebraska. The primary purpose of our study was to evaluate drinking water nitrate exposure and agricultural exposures as risk factors for these tumors. A secondary purpose of the study was to compare risk factors for adenocarcinomas of the esophagus, stomach cardia and distal stomach. The descriptive epidemiology of adenocarcinomas of the distal stomach and esophagus differ. Stomach cardia tumors share many characteristics with the adjacent esophageal tumors, including an increasing incidence in the United States and in other developed countries (Blot et al., 1991; Powell and McConkey, 1990; Møller, 1992). We now present results for meat and gravy intake, meat cooking methods and doneness preference, informa- tion which was ascertained as part of the dietary assessment. METHODS A population-based case-control interview study of stomach and lower esophageal cancers was conducted in eastern Nebraska. For efficiency and to reduce the cost of the study, controls were randomly selected from a group of controls from a previous population-based case-control study of hematopoietic cancers in Nebraska (Zahm et al., 1990) and were re-interviewed at the time of the case interviews. Cases Cases were white men and women aged 21 years or older, who had been newly diagnosed with adenocarcinoma of the stomach or esophagus (ICD-O codes 150, 151) between July 1, 1988, and June 30, 1993. Cases were limited to whites because the control group excluded other ethnic groups due to expected small numbers. Cases were residents of 66 counties in eastern Nebraska at the time of the interview. Cases who were not resident in Nebraska during 1983–1985 (when controls were identified) were excluded (n 5 6) from the analyses so that the same residence criteria applied to cases and re-interviewed controls. Cases from 1988 through 1990 were identified from the Ne- braska Cancer Registry. Cases from 1991 through June 30, 1993, were identified by review of discharge diagnoses and pathology records at the 14 hospitals in Omaha, Lincoln and Grand Island. These 14 hospitals accounted for about 90% of the stomach and esophageal cancer diagnoses in the eastern 66 counties. *Correspondence to: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6130 Executive Blvd. EPN-418, Bethesda, MD 20892-7364, USA. Fax: (301) 402-1819. Received 17 September 1996; revised 18 November 1996 Int. J. Cancer: 71, 14–19 (1997) r 1997 Wiley-Liss, Inc. ² This article is a US Government work and, as such, is in the public domain in the United States of America. Publication of the International Union Against Cancer Publication de l’Union Internationale Contre le Cancer