The widespread use of pesticides in Egypt, the high incidence of colorectal can- ... pilot study to describe serum organochlorine levels among 31 Egyptian ...
Serum Organochlorine Pesticide Levels in Patients
with Colorectal Cancer in Egypt AMR S. SOLIMAN Department of Community Medicine Menofeia Faculty of Medicine Menofeia, Egypt and Department of Epidemiology University of Texas M.D. Anderson Cancer Center Houston, Texas MARY ANN SMITH SHARON P. COOPER University of Texas School of Public Health Houston, Texas KADRY ISMAIL Tanta Cancer Center Tanta, Egypt HUSSEIN KHALED The National Cancer Institute Cairo University Cairo, Egypt
SOHAIR ISMAIL Department of Radiotherapy Ain Shams University Cairo, Egypt R. SUE MCPHERSON University of Texas School of Public Health Houston, Texas IBRAHIM A. SElFELDlN Tanta Cancer Center Tanta, Egypt MELISSA 1. BONDY Department of Epidemiology University of Texas M.D. Anderson Cancer Center Houston, Texas
ABSTRACT. The widespread use of pesticides in Egypt, the high incidence of colorectal cancer in Egyptian children and young adults, and the published U.S. case reports in which pesticides have been connected with colorectal cancer led the authors to investigate the possible association between organochlorines and colorectal cancer. The authors conducted a pilot study to describe serum organochlorine levels among 31 Egyptian colorectal patients and 17 controls. High levels and large interindividual variability of p,p’-dichloro-diphenyldicholoroethylene (DDE), dichloro-diphenyl-trichloroanthane (DDT), P-hexachlorocyclohexane (P-HCH), and hexachlorobenzene (HCB) levels were found among most subjects, especially those from rural areas. Farming and aging were each associated positively with high serum organochlorines. Colorectal cancer patients had higher serum organochlorines levels than controls. The high levels of organochlorines reported and their relation to age, residence, occupation, and disease status justify further study of the possible association between organochlorine pesticides and colorectal cancer in a larger population in Egypt.
ORGANOCHLORINE PESTICIDES, which are still used in agriculture in many parts of the world, have been implicated in the pathogenesis of many adverse health effects, including Although the risk factors for colorectal cancer in older subjects have been studied in many locations, these factors have not been studied so thoroughly in children or young adults. In the few studies conducted on younger subjects, investigaNovernber/Decernber 1997 [Vol. 52 (No. 611
tors focused mainly on genetic factor^.^-^ Chemical exposure may be related to colorectal cancer in young patients,’~~but in only one study did investigators measure serum organochlorine pesticides. In that study, which included 10 adolescent colorectal cancer patients exposed to pesticides and herbicides in Mississippi Delta farm region^,^ investigators reported high serum levels of dichloro-diphenyl-triachloroanthane 409
(DDT) residues and P-hexachlorocyclohexane (P-HCH) in patients. However, that study was characterized by a small sample size and it lacked a comparison group, which was needed by investigators to test the hypothesis that organochlorines are associated with increased risk of colorectal cancer in young patients. In Egypt, approximately 22% of all colorectal cancers occur in children and young adults under 30 y of We confirmed this by review of patients’ charts, which spanned 3-10 y, from four cancer hospitals. These hospitals included the two major cancer centers of Egypt (The National Cancer Institute [NCI] in Cairo and Tanta Cancer Center [TCC] in the mid-Nile Delta region) and two major university hospitals (Assiut University in South Egypt and Ain Shams University in Cairo). In our review, we noted that among the four hospitals, the average frequency of colorectal cancer relative to total colorectal cancer cases was 22-25% in subjects less than 30 y of age and was 3 5 4 0 % in subjects less than 40 y of age.I3 These rates were 4-5 times the 2-6% rate reported among subjects less than 40 y of age in Western countries,14 even after we considered the population age structure of Egypt and Western countries. On the other hand, climatic factors, crop types, and pesticides and herbicides found in Egypt are similar to those noted in the Mississippi study, from which we gleaned the hypothesis that pesticides are causally related to colorectal ~ a n c e r . Furthermore, ~,~ in studies from Egypt, investigators reported that they found milk and fish samples contaminated with high levels of DDT residues and HCHl5-l7; however, the health effects of these exposures have not been detailed. We therefore conducted a pilot study to describe serum organochlorine pesticide levels among a sample population of Egyptians who were colorectal cancer patients and general population controls.
Material and Method In this study, we recruited 31 patients (19 males, 12 females) and 17 controls (1 2 males, 5 females) during March and April 1996. We recruited patients and controls from three cancer hospitals in Egypt: ( 1 ) TCC (12 cases, 1 1 controls); (2) NCI (5 cases, 1 control); and (3) Radiotherapy unit of Ain Shams University Hospital (1 4 cases, 5 controls). Colorectal cancer patients (a) were treated at the time of the study or had been treated at those centers, (b) were alive, and (c) agreed to participate in this study. Controls, who were apparently healthy friends of other cancer patients who had no cancer, lived in geographical areas other than those of the colorectal cancer patients. We intentionally recruited controls from other geographical-but similar-rural and urban areas to avoid sampling controls who had been exposed to the same dose of pesticides in the same geographical locales as cases. Given that the controls in our study were from areas proximal to, but not exactly the same as, those areas the cases were from, we assumed the controls could have been exposed to pesticides, but at levels that differed from those to which the cases were exposed. 410
The mean ages of patients and controls (*l standard deviation) were 42 r 12.4 y and 38 14.5 y, respectively. Patients and controls represented both urban and rural areas and many different occupations. Interviewers used a standard interviewer-administered questionnaire to glean the following information from each participant: current and past occupational history, duration and activities of each job, types of pesticides used, and crops grown. Also collected were family histories of colorectal cancers and other cancers, and medical histories of predisposing conditions (e.g., familial adenomatous polyposis, ulcerative colitis, other gastrointestinal diseases). We measured weights and heights of patients and controls, and we calculated body mass index (BMI)as (weight in kg/height2 in m) ( 1 0 O ) . l 8 We drew 7-10 ml of blood from each patient and control subject, and they were stored in sterile Vacutainer8 tubes. Blood was allowed to clot for 15-30 min before serum separation, by centrifugation at 1 300 rpm for 10 min. Not less than 3 ml of clear serum from each sample was then transferred to glass tubes. Each serum sample was labeled with the patient’s name, identification number, clinic name, and collection date. Samples were frozen at -20 “C until they were transported (i.e., within 3 wk) to Accu-chem Laboratories in Richardson, Texas, for testing. Samples were hand-carried in dry ice in transport from Egypt to the United States. At Accuchem laboratories, serum samples were thawed at room temperature and mixed thoroughly. An internal standard was then added. Samples were separated by repeated hexane extraction, evaporated to dryness under nitrogen, and then reconstituted in hexane. Second aliquots were analyzed by gas chromatography according to the method of Dale et aI.l9 We used high-resolution gas chromatography/eIectron capture (GUECD), with a detection limit of 0.3 ng/ml (ppb) in the serum, to analyze a panel of 19 organochlorines in the serum. We tested each serum specimen for the presence of the following components: a-chlordane, y-chlordane, oxychlordane, heptachlor, heptachlor epoxide, trans-nonachlor, a-HCH, P-HCH, lindane (y-HCH), 6-HCH, aldrin, endrin, dieldrin, hexachlorobenzene(HCB), endosulfan I, endosulfan II, p,p’-dichlorodiphenyldicholoroethylene (DDE), DDD, and p, p’-d ichlorodipheny It richloroethane (DDT). We estimated total serum DDT among study subjects as the sum of p,p’-DDT, p,p‘-DDE, and p,p’-DDD levels. This combination approximated total serum DDT.20 We used the logarithms (base 10) of total serum DDT, p,p’-DDT, p,p’-DDE, p,p’-DDD, P-HCH, and HCB as the continuous exposure because the distribution of serum levels of these pesticides was asymmetric. We used the SAS statistical program2’ to test (Student’s t) differences between means of logarithms of serum pesticide levels.
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Results The results of our study varied widely with respect to distribution of organochlorine pesticide levels and the exceptionally high values found among the study subArchives of Environmental Health
jects. We detected four organochlorine residues (i.e., DDE, DDT, P-HCH, and HCB) in most samples tested. Some subjects had levels (a) up to 50 times the rates reported in the United States for DDT and DDE and (b) up to 300 times those reported in the United States for P-HCH (Table 1). It is noteworthy that subjects with the highest levels of DDE also had the highest levels of p,p’DDT and P-HCH. Moreover, when we excluded subjects with extreme values from the analysis, the mean values for DDT and P-HCH only dropped from 67.7 ppb to 57.9 ppb and from 17.6 ppb to 11.2 ppb, respectively. Also, organochlorine levels increased with age, as evidenced by correlation coefficients of .5, .42, .41, and .40 for the relationship between age and DDE, DDT, P-HCH, and HCB, respectively. Although we found four organochlorines in detectable amounts in most serum samples, we found other organochlorines in detectable amounts in only a very few samples: a-HCH in 5 samples (0.7, 1.O, 1.2, 2.1, and 2.9 ppb, respectively); trans-nonachlor in 2 samples (0.4 ppb and 0.5 ppb, respectively); endosulfan II in 1 sample (0.7 ppb); and DDD in 1 sample (0.6 ppb). None of these samples had high levels of DDE, p,p’-DDT, P-HCH, or HCB. Organochlorine levels in our study population varied not only between subjects but also by place of residence. Rural residents had higher serum organochlorine levels than urban residents. This statistically significant rural-urban difference remained for levels of DDT, DDE, and p,p’-DDT (Table 2), as well as for levels of PHCH (Table 3). Levels of HCB were higher in rural areas than in urban ones, but this difference was not different statistically (Table 3). Another factor that differentiated levels of serum organochlorine between subjects was occupation (i.e., farming). Subjects who had worked previously in farm occupations had higher DDT and P-HCH levels than
Table 1.-Serum
those who had never worked in agriculture (Table 4). This association remained among all study subjects and at all ages (Table 4), and the difference was statistically significant for DDT and HCH among total subjects and subjects 40 y of age and older. Pesticide levels were higher in patients than controls, regardless of gender, and they were higher among colon cancer patients than rectal cancer patients (Table 5); these differences, however, were not statistically significant. Controls were heavier than patients (mean BMI standard deviation: 25.2 2.0 kg and 23.5 4.5 kg for controls and patients, respectively).The median BMI for controls was 25.9 and for patients, 21.8. Also, the BMI ranged from 21.5 to 28.1 for controls and from 16.7 to 31.9 for patients. Correlation coefficients of total DDT, DDT, DDE, P-HCH, and HCB with BMI of patients were .04, .04, .04, -.01, and .03, respectively; the coefficients for controls were .31, .56, .29, .49, and .001, respectively. Information taken from family histories of patients revealed 3 patients (10%) who had a family history of colorectal cancer and an additional 3 patients (10%) who had a family history of other types of cancer. Neither patients nor controls reported histories of familial adenomatous polyps, ulcerative colitis, prolonged gastrointestinal disturbances, or chronic dysentery.
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Discussion In this study, we attempted to describe the organochlorine pesticide levels among Egyptians and to examine those levels among two groups of colorectal cancer patients (i.e., those younger than 40 y of age and those older than 40 y of age) and a third group of control subjects who had no cancer. Our findings were interesting. First, the Egyptians in our study had exceptionally higher DDE and P-HCH organochlorine levels than individuals
Pesticide levels among Egyptian Subjects and U.S. Comparison Populations
Mean Median Standard deviation Detection limit Maximum Detected cases (YO) U.S. comparison-NHANES I1 (1976-1 980) mediant 95th percentile Average detection limits+
DDT* (ppb)
DDE (ppb)
p,p,-DDT (PPb)
P-HCH (PPb)
HCB (PPb)
67.7 39.3 109.7
63.8 38.0 99.1 c 0.3 642.7 98 12.6 12.6 52.9 3.2
3.9 0.9 11.5 < 0.3 71.4 73 Trace
17.6 5.6 46.8 < 0.3 316.9 92 Trace
0.5 0.4 0.6 < 0.3 2 .o 65 Trace
2.7 0.4
2.4 0.5
Trace 0.5
714.1 98
tSource: U.S. Environmental Protection Agency, Lower Rio Grande Valley Environmental Monitoring study, Report to the Community on the Pilot Project, June 1994. +Source: Information based as average of 1 000 samples analyzed by Accu-chem laboratories from different internationalstudies. Notes: DDT = dichloro-diphenyl-trichloroanthane,DDE = p’p’-dichloro-diphenyl-dichloroethylene, P-HCH = P-hexachlorocyclohexane, and HCB = hexachlorobenzene. *DDT = DDE + p, p’-DDT + DDD.
NovemberlDecember 1997 Nol. 52 (No. 6)l
41 1
Table 2.-Serum
DDT*, DDE, and p,p,-DDT levels among Egyptian Subjects, by Residence
DDTt Rural Urban Mean Median Standard deviation Minimum Maximum U.S. ComparisonNHANES II (1976-1980) Median5 95th percentile Average detection limits*
’ I
103.6 61.2 144.9 NDS 714.1
p,p,-DDTt Rural Urban
96.8 57.5 130.2 3.9 642.7
30.8 23.6 28.9 ND 125.3
6.9 1.6 15.8 ND 71.4
0.8 0.5 1.1 ND 4.5
12.6
12.6
Trace
trace
52.9 3.2
52.9 3.2
2.7 0.4
2.7 0.4
§Source: U.S. Environmental Protection Agency, Lower Rio Grande Valley Environmental Monitoring study, Report to the Community on the Pilot Project, June 1994. #Source: Information based as average of 1 000 samples analyzed by the laboratories from different international studies. Notes: DDT = dichloro-diphenyl-trichloroanthane, DDE = p’p’-dichloro-diphenyl-dichloroethylene, P-HCH = P-hexachlorocyclohexane,and HCB = hexachlorobenzene. *DDT = DDE + p, p’-DDT + DDD. tp < .05,using means of logarithms. SND = not detected.
studied in any investigation in the United state^.^,^^,^^ Second, among our Egyptian subjects, rural residents had significantly higher DDT and P-HCH levels than urban residents. Third, agriculture was associated with increased levels of DDT and P-HCH in patients who were in both age groups (i.e., over and under 40 y of age). Fourth, DDT and P-HCH levels increased with age. Fifth, colorectal cancer patients had higher levels of these serum organochlorines than did controls. Older patients and controls had higher levels than younger cases and controls. The high serum organochlorine levels in Egyptians may be explained in several ways. In Egyptian studies, 15-1 7 researchers have reported high levels of organochlorine in some foods (e.g., milk, dairy products, fish). The lack of mechanization in Egyptian agriculture, improper application of pesticides, and deficient methods of protecting against possible hazards associated with the use of chemicals in agriculture increase the chances of human exposure to pesticide^.^^ The muddy soil and humid environment of Egypt favor high absorption of organochlorines and continuous availability of such compounds in the e n ~ i r o n m e n t Finally, .~~ obesity is very prevalent among Egyptians25; this, combined with the fact that organochlorines are stored in adipose tissue26and adipose levels correlate significantly with serum levels,27may explain the high serum organochlorine levels in Egypt. The relationship between obesity and high organochlorine levels was not clear in this study, because all the patients indicated that they had lost weight during the period of disease symptoms (i.e., periods ranging from 1 to 12 mo) or during the postoperative period. Weight loss might have mobilized organochlorines from the adipose tissues to the serum27,28 and may have masked the association between organochlorine and 412
31.6 23.9 29.9 ND 129.8
DDEt Rural Urban
obesity among patients. This conclusion is reinforced by the higher correlation coefficients between BMI and serum organochlorine levels in controls than in patients in this study. Our results also suggest that place of residence may play a role. In our Egyptian study population, serum organochlorine levels were higher among rural subjects than among urban ones. In comparison, U.S. rural populations, which may frequently come into contact with a variety of pesticides and which grow crops in ways and in a climate similar to those in Egypt, also showed high levels of serum organochlorines-but at levels below those reported in E g ~ p t . ~ , ~ Rural residence and agricultural occupations may be surrogates for serum organochlorine levels; therefore, they may be correlated highly with DDE exposure and the possible associated colorectal cancer risk.29,30 However, urban residents in this study had relatively high serum organochtori ne levels. Although these levels were lower than those in iural Egyptian residents, the levels were relatively high, compared with levels reported in the United States. Many factors could explain the high levels that exist in urban Egyptian residents, including ingestion of organochlorine-contaminated food^'^-'^; contact with bioaccumulated DDT compounds in contaminated waterways via runoff from fields3’; or breast f ~ d i n g , which ~ ~ , ~i s~often practiced until children reach 2 y of age. Also, some urban residents in this study reported that they had previously lived in or visited rural areas. We found four types of organochlorines-DDE, DDT, P-HCH, and HCB-in most samples in this study; however, other organochlorines (e.g., aldrin, dieldrin), which were reported in earlier studies and were found in Egyptian milk, dairy products, and fish,15-17 were not detected at all. Perhaps these discrepancies resulted Archives of Environmental Health
Table 3.-Serum P-HCH and HCB Pesticide Levels among Egyptian Subjects, by Residence P-HCH*
Mean Median Standard deviation Minimum Maximum U.S. ComparisonNHANES II (1976-1 980) medians 95th percentile Average detection limits*
Table 4.-Average DDT and P-HCH Serum Pesticide Levels*, by Age and History of Farming Ever worked in farming
HCB
Rural
Urban
Rural
Urban
Age group
31.2 12.4 63.9 NDt 316.9 Trace
4.0 3.3 3.4 ND 11.8 Trace
0.6 0.5 0.6 ND 2.9 Trace
0.4 0.4 0.5 ND 2.0 Trace
< 40 y
2.4
2.4
Trace
Trace
0.5
0.5
0.5
0.5
+Source: U.S. Environmental Protection Agency, Lower Rio Grande Valley Environmental Monitoring Study. Report to the Community on the Pilot Project, June 1994. §Source: Information based as average of 1 000 samples analyzed by the laboratories from different international studies. Notes: DDT = dichloro-diphenyl-trichloroanthane, DDE = p’p’-dichloro-diphenyl-dichloroethylene, P-HCH = P-hexachlorocyclohexane, and HCB = hexachlorobenzene. * p value c .05, using means of logarithms. t N D = not detected.
No. Subjects Mean DDT+ Mean B-HCH Mean HCB 40+ y No. Subjects Mean DDTt Mean B-HCH Mean HCB All ages No. Subjects Mean DDTt Mean B-HCH Mean HCB
Yes
No
P+
9 37.2 9.3 0.2
14 19.1 2.3 0.4
NSS
16 136.7 41.6 0.8
9 50.9 7.2 0.6
25 100.9 29.9 0.6
23 31.6 4.2 0.5
NS NS .02
.008 NS .003 ,005 NS
Notes: DDT = dichloro-diphenyl-trichloroanthane, DDE = p’p‘-dichloro-diphenyl-dichloroethylene, P-HCH = P-hexachlorocyclohexane, and HCB = hexachlorobenzene. *Levels are given in parts per billion (ppb) units. tp values were calculated, using mean algorithms of DDT, PHCH, and HCB. +DDT = DDE + p,p’-DDT + DDD. SNS = not significant.
‘rom the (a) different study locales in our study, as well Table 5.-Average DDT and P-HCH Serum Pesticide Levels*, IS in earlier studies; (b) related variations in crops and by Disease Status, PathologicalType of Cancer, and Gender .ypes of pesticides used in the different study locales; and (c) small sample size of our study. In our study, DDTt P-HCH organochlorine levels increased with age-a result that X SD Strata R SD comports with those of other s t ~ d i e s . It~should ~ , ~ ~be ~~~ noted, however, that young subjects in our study also Disease status+ had high organochlorine levels. Cancer ( n = 3 1) 71.0 131.9 21.5 57.4 In our study, patients with colon cancer had higher Noncancer (n = 17) 10.5 13.0 61.5 51.6 serum organochlorine levels than patients with rectal Rectal ( n = 15) 48.4 65.3 16.8 22.8 Colonic ( n = 16) 92.3 172.6 26.0 77.9 cancer. This finding, however, was not in agreement Gender+ with the reported observation of rectal, rather than Male ( n = 31) 68.5 126.3 20.1 56.8 colon, cancers among pesticide users in Italy,30and it Female ( n = 17) 66.2 73.6 13.1 18.6 could not be explained by the unclear, existing literature that contains information about possible carcinoNotes: DDT = dichloro-diphenyl-trichloroanthane, DDE = gens known to affect different segments of the colon p’p’-dichloro-diphenyl-dichloroethylene, P-HCH = P-hexaand rectum.34In this analysis, the small sample size led chlorocyclohexane, and HCB = hexachlorobenzene. us to treat all colon segments collectively. ‘Levels are given in parts per billion (ppb) units. Other confounders or factors that might be related tDDT = DDE + p,p’-DDT + DDD. Sp values not significant. to this young-onset colorectal cancer are hereditary factors, parasitic infestation, and related treatment. Genetic and hereditary factors include familial polySchistosomiasis and amebiasis are two endemic parapos is, Gardener’s disease, chronic enteritis, and nonhereditary colorectal cancer (HNPCC). Only 1 sitic diseases in Egypt that are possibly related to colorectal cancer. Although a possible association between patient reported a family history suggestive of Schistosorna rnansoni and colorectal cancer has been HNPCC, and each of 2 additional patients reported suggested in only two s t ~ d i e s , ~other ~ , ~ ~investigators having 1 family member who had colorectal cancer. have reported that S. rnansoni may not be related to colAlthough each of these 3 patients may have had a orectal cancer because (a) the incidence of colorectal hereditary susceptibility, environmental chemicals cancer versus schistosomiasis in Africa ~ a r i e s , and ~ ~ (2) ,~~ may have facilitated the activation of this genetic susceptibility and the appearance of phenotypic characthe uniform distribution of colorectal cancer in young Egyptians in all geographical areas of Egypt does not teristics of the disease.35 November/December 1997 Wol. 52 (No. 6)]
413
2. International Agency for Research on Cancer (IARC). DDR and match the predominance of S. Mansoni in the Nile Delta associated compounds. IARC Monograph on Evaluation of Carregion of Egypt.13 With respect to amebiasis, in only one cinogenic Risk to Humans. Geneva, Switzerland: World Health study was it found in one-third of 11 Nigerian colorectal Organization, 1991; pp 179-49, vol 53. cancer patients under age 30 y.40 3. Raymond PL, Skelton DS, Hsu HSH. Young patients with colorectal cancer: the University of Mississippi Medical Center Metronidazole, a drug commonly used to treat amebiexperience, 1970-1 990. J Miss Med Assoc 1991; 32(8):298-304. asis, increased colonic tumors in the 1,2-dimethylhy4. Martin EW, Joyce S, Lucas J, et al. Colorectal carcinoma in drazine-treated rat model for colon cancer; however, patients less than 40 years of age: pathology and prognosis. Dis doses were much higher than those used to treat human Colon Rectum 1981; 24:25-28. provided a dose of metronDavis et 5. MacGillivray DC, Swartz SE, Robinson AM, et al. Adenocarcinoma of the colon and rectum in patients less than 40 years of age. idazole to rats that approximated the therapeutic dosage Surg Gynecol Obstet 1991; 172:l-7. used in maintenance therapy of inflammatory bowel syn6 . Palmer ML, Herrera L, Petrelli NJ. Colorectal adenocarcinoma in drome, and the number of colonic tumors was increased patients less than 40 years of age. Dis Colon Rectum 1991; 34: in rats that received dimethylhydrazine. The evidence 343-45. from human studies, however, does not support an asso7. Pratt CB, Rivera G, Shanks E, et al. Colorectal carcinoma in adociation between metronidazole and colon ~ a n c e r . ~ ~ , ~ ~ lescents: implications regarding etiology. Cancer 1977; 40: 2464-72. Furthermore, in one case-series report on patients with 8. Pratt CB, George SL, O'Connor D. Adolescent colorectal cancer Crohn's disease, other cancers occurred4'jonly after 2+ y and dioxin exposure (letter). Lancet 1987; 2:803. of metronidazole intake. Although metronidazole is com9. Caldwell CG, Cannon SB, Pratt CB, et al. Serum pesticide levels in patients with childhood colorectal carcinoma. Cancer 1981; monly used by individuals in Egypt to treat amebiasis and 48:774-78. giardiasis, it is usually used intermittently and for short 10. About-El-Eneine A, Beshara F, Abdou L, et al. Colorectal Cancer periods. None of the subjects we interviewed, however, below Thirty in Alexandria University hospitals. Alexandria, mentioned symptoms of chronic ulcerative colitis or proEgypt: Bulletin of the Alexandria Faculty of Medicine, 1986; longed use of metronidazole. In light of these data, we do 190:1171-78. 1 1 . El-Choniemy E, Moustafa H, Yammini MM, et al. Colorectal carnot believe that parasitic infections and the use of cinoma in Egyptian patients younger than 30 years. J Egypt Nat metronidazole were confounders in our study. However, Cancer lnst 1989; 4:95-103. given the controversy surrounding them, these factors 12. Shawky A, Rezk M, Ali MM, et al. Colorectal carcinoma before should be investigated further as possible risk factors for and after the age of forty years: clinicopathological study. New Egypt J Med 1992; 6:1870-73. colorectal cancer in young Egyptians. 13. Soliman AS, Bondy ML, Levin B, et al. Colorectal cancer in In conclusion, the results of our study showed excepEgyptian patients under 40 years of age. Int J Cancer 1997; tionally higher levels of organochlorine pesticides in our 71 :26-30. subjects than have been reported in other countries. As 14. Heys SD, OHanrahanTJ, Brittenden J, et al. Colorectal cancer in well, there was a wide variation in interindividual serum young patients: a review of the literature. Eur J Surg Oncol 1994; 20:225-31. organochlorine levels. Of course, such a small sample 15. Dogheim SM, Almaz MM, Kostandi SN, et al. Pesticide residues size necessarily limits the generalization of these results in milk and fish samples from upper Egypt. J Assoc Off Anal to Egypt. Our study also directs attention to the possible Chem 1988; 71 2374-76. association among farming, rural residence, and higher 16. Dogheim SM, Nasr EN, Almaz MM, et al. Pesticide residues in serum organochlorine levels. Much more research is milk and fish samples collected from two Egyptian governorates. J Assoc Off Analy Chem 1990; 73:19-21. needed in a larger Egyptian population sample that 17. Amr MM, Moursy AW, Hafez RS, et al. Pesticide residues in milk would enable investigators to further investigate and dairy products in Egypt. Egypt J Occup Med 1995; organochlorine level differences between rural and 19~147-68. urban populations in Egypt and their association with 18. Frankel HM. Determination of body mass index. JAMA 1986; colorectal cancer. 255:1292.
* * * * * * * * * * The authors thank Dr. Mohamed-El-Sobky of the Department of Occupational Medicine, Menofeia University, Egypt, for his comments on the manuscript; Dr. John Laseter of Accu Chem Laboratories for his help with the laboratory analysis; Jude Richard of the Department of Scientific Publications, M.D. Anderson Cancer Center, for his editorial comments; and Joyce Brown of the Department of Epidemiology, M.D. Anderson Cancer Center for her secretarial help. Submitted for publication October 1 1 , 1996; revised; accepted for publication June 1 1 , 1997. Requests for reprints should be sent to Amr S. Soliman, M.D., Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, 151 5 Holcombe Blvd., Box 189, Houston, TX 77030.
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