1 McLaughlin Centre for Population Health Risk Assessment, Institute of Population Health, University of Ottawa, Ottawa, ON, Canada.
2 Centre de Recherche, Institut Universitaire de Gériatrie de Montréal, Montreal, QC, Canada.
3 Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy.
4 Epidemiology Research Unit, Research Centre, CHUM-Hôtel-Dieu, Montreal, QC, Canada. E-mail: parviz.ghadirian{at}umontreal.ca
SirsIn their commentary entitled Can dietary fatty acids affect colon cancer risk?1 Drs Leitzmann and Giovannuccihave critically evaluated our recently published paper on the association between specific fatty acids and the risk of colorectal cancer,2 and raised some important points. They have clearly justified that diet is not the only source of many fatty acids, so that isolating diet-related fatty acid effects on colon cancer is complex. We agree. In fact, very few nutrients are provided exclusively by diet. Some essential nutrients are synthesized endogenously to a certain extent, in addition to being consumed in foods or supplements.
Drs Leitzmann and Giovannucci have suggested that other factors in dairy products, such as calcium, rather than medium chain fatty acids may have accounted for the inverse associations observed between these fatty acids and colorectal cancer risk. Based on our study, the main sources of medium chain fatty acids among French-Canadians were dairy products, and there is evidence that dietary calcium intake is associated with reduced colorectal cancer risk. It has been hypothesized thatthe protective effect of calcium could be due to the formationof calcium soaps in the colon, which neutralize the bowel-irritating effect of bile acids and fatty acids.3 It is indeed possible that calcium may have contributed to this effect since a significant inverse association of dietary calcium with colon carcinoma, with approximately 30% risk reduction, was found in this population.4
Another point made by Drs Leitzmann and Giovannucci was that the increased colorectal cancer risk associated with arachidonic acid, which we observed in our study, may have reflected a correlated component of meat intake. There is strong evidence that high consumption of red meat, especially when welldone and highly cooked, increases the risk of colorectal cancer, particularly in individuals who also smoke and are genetically susceptible.5 We disagree with their hypothesis, however, since in our study we found that the main arachidonic acid sources were poultry products (white meat), which have not been consistently associated with an increase in colorectal cancer risk.
Drs Leitzmann and Giovannucci have also suggested an alternative explanation for the gender-specific variations observed in our study. Since a higher proportion of ever smokers were likely to be male, they proposed that smoking-related colon cancers among men might have diluted the relative risks associated with specific fatty acid intakesif these cancers develop through a pathway different from that of fatty acid intake. We addressed this point by adjusting for smoking, which did not substantially change our findings. In addition, we investigated the effect modification by smoking status in both genders. We noted important changes in females, while our findings were unaltered in males, ruling out their proposition. For example, alpha-linolenic acid was associated with a 22% reduction in colorectal cancer risk. Among women who never smoked, this inverse association became stronger and the trend was highly significant (OR = 0.31; 95% CI: 0.13, 0.77; P = 0.002), whileno association was observed among those who ever smoked (OR = 1.45; 95% CI: 0.69, 3.04; P = 0.486).
Finally, underlying mechanisms regarding the possible roleof specific fatty acids in the aetiology of colorectal cancer have been proposed,6 so that the hypothesis generated by our data, and stressed by Drs Leitzmann and Giovannucci, that diet-related individual fatty acids could affect colorectal cancer is promising and deserves further evaluation.
References
1 Leitzmann MF, Giovannucci EL. Commentary: can dietary fatty acids affect colon cancer risk? Int J Epidemiol 2003;32:20910.[CrossRef][ISI][Medline]
2 Nkondjock A, Shatenstein B, Maisonneuve P, Ghadirian P. Assessment of risk associated with specific fatty acids and colorectal cancer among French-Canadians in Montreal: a case-control study. Int J Epidemiol 2003;32:20009.[CrossRef][ISI][Medline]
3 Newmark HL, Wargowich MJ, Bruce WR. Colon cancer and dietary fat, phosphate, and calcium: a hypothesis. J Natl Cancer Inst 1984;74: 132325.
4 Ghadirian P, Lacroix A, Maisonneuve P et al. Nutritional factors and colon carcinoma. A case control study involving French Canadians in Montreal, Quebec, Canada. Cancer 1997;80:85864.[CrossRef][ISI][Medline]
5 Le Marchand L, Hankin JH, Pierce LM et al. Well-done red meat, metabolic phenotypes and colorectal cancer in Hawaii. Mut Res 2002; 506507:20514.[ISI]
6 Nkondjock A, Shatenstein B, Maisonneuve P, Ghadirian P. Specific fatty acid and human colorectal cancer: an overview. Cancer Detect Prev 2003;27:5566.[CrossRef][ISI][Medline]