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Water Intake and Cancer Prevention

Child Health Center and Pediatric Hematology and Oncology, Soroka Medical Center, Beer Sheva, Israel

To the Editor:

In his interesting article on clinical trials for cancer prevention, Dr. Peter Greenwald [1] mentioned factors relevant in cancer prevention, such as tobacco and alcohol use, sun exposure, sexual behavior patterns, physical activity, obesity, and diet. However, the role of fluid intake was not mentioned, and we trust that this factor deserves more attention in the current research of cancer prevention.

Malignancies mostly cited in connection with fluid intake are bladder cancer, colorectal cancer, and breast cancer. D. Michaud et al [2] found a statistically significant correlation between total fluid intake and the risk of bladder cancer in their prospective study with 47,909 participants during a period of 10 years. The total daily fluid intake was inversely associated with the risk of bladder cancer. The multivariable relative risk was 0.51 (95% CI, 0.32 to 0.80) for the highest quintile of total daily fluid intake (> 2,531 mL/d) as compared with the lowest quintile (< 1,290 mL/d). When fluid intake was modeled as a continuous variable, the risk of bladder cancer decreased by 7% for every increment of 240 mL in daily fluid intake. Study participants in the highest quintile of fluid intake had a 49% lower incidence of bladder cancer than those in the lowest quintile. This finding was described by other authors [3,4] and is consistent among all regions of the United States and equal among smokers and nonsmokers. According to the hypothesis by R. Oyasu et al [5], the concentrated urine and the less frequent micturition increases the exposure of the bladder urothelium to urinary carcinogens, promoting the development of bladder cancer [6]. This hypothesis was supported by a study in which dogs exposed to known urinary bladder carcinogen (4-aminobiphenyl) had significantly increased urothelial levels of DNA adducts when the average frequency of voiding was reduced [7].

J. Shannon et al [8] observed an association between food groupings including water intake and the risk for adenocarcinoma of the colon in men and women aged 30 to 62 years. Water intake alone was significantly associated with reduced risk of colon cancer among women (odds ratio [OR] for 5 glasses of water/d v 2 glasses of water/d, 0.55; 95% CI, 0.31 to 0.99; P for trend = .004) and for men (OR for 4 glasses of water/d v 1 glass of water/d, 0.68; 95% CI, 0.38 to 1.22; P = .16). In a hospital-based case-control study on a total of 163 patients (age 33 to 80 years) with histologically confirmed primary colorectal cancer in Taiwan, Tang et al [9] found an inverse dose-response relationship between water intake and colorectal cancer even after adjustment for total calories, dietary factors, and smoking status. Significant statistical evidence was observed between patients with rectal cancer among men in the highest tertile of water intake (OR, 0.08; 95% CI, 0.02 to 0.35) compared with those in the lowest tertile (OR, 1.0; P = .0005). The OR for colorectal cancer among men in the lowest tertile of water consumption was approximately four-fold that among men in the highest tertile. This finding is supported by an animal study [10] demonstrating the role of slow bowel-transit time and the development of neoplasms. Rats were treated with 1,2-dimethylhydrazine, and constipation was induced in the experimental group by reducing water intake throughout the experiment. On kill there was an increased number of colonic neoplasms in the experimental group (P = .02). This suggests that increased water intake may have an important role in reducing colon cancer risk by decreasing bowel transit time, reducing the mucosal contact with carcinogens, and decreasing the concentration of carcinogens.

Stookey et al [11] conducted a hospital-based case-control study to investigate the hypothesis that water drinking protects against breast cancer. They compared a group of women with newly diagnosed histologically confirmed breast cancer (n = 44) with controls (n = 55) with non-neoplastic conditions and no history of malignancies in the same hospital for their dietary food and beverage consumption. In logistic regression analysis, water drinking appeared strongly inversely and significantly associated with breast cancer risk. The unadjusted OR for water drinking was 0.31 (95% CI, 0.13 to 0.72), which remained unaltered after age adjustment. This risk estimate represented a 4.7-fold difference in the odds of exposure between cases and controls. The authors stated that water intake may play a role in limiting carcinogenesis via water requirement-related mechanisms. They hypothesized that subclinical or "chronic" dehydration may compromise intracellular water, alter cellular concentrations, affect the activity of enzymes in metabolic regulation, and inhibit cellular carcinogen removal [12].

These studies support the beneficial effect of water drinking on cancer prevention in addition to other lifestyle factors, such as smoking avoidance or cessation, moderation of alcohol consumption, and treatment or prevention of obesity. Future clinical and epidemiologic studies might help to further define the role of water intake for cancer prevention.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

View larger version (16K): [in this window] [in a new window]   Fig 1. Age-specific incidence rates (A) and breast cancer-specific survival (B). LABC, locally advanced breast carcinoma; IBC, inflammatory breast cancer; EOD, extent of disease.

1. Greenwald P: Cancer prevention clinical trials. J Clin Oncol 20:14S-22S, 2002 (suppl 18)

2. Michaud DS, Spiegelman D, Clinton SK, et al: Fluid intake and the risk of bladder cancer in men. N Engl J Med 340:1390-1397, 1999[Abstract/Free Full Text]

3. Bitterman WA, Farhadian H, Abu Samra C, et al: Environmental and nutritional factors significantly associated with cancer of the urinary tract among different ethnic groups. Urol Clin North Am 18:501-508, 1991[Medline]

4. Wilkens LR, Kadir MM, Kolonel LN, et al: Risk factors for lower urinary tract cancer: The role of total fluid consumption, nitrites and nitrosamines, and selected foods. Cancer Epidemiol Biomarkers Prev 5:161-166, 1996[Abstract/Free Full Text]

5. Oyasu R, Hopp ML: The etiology of cancer of the bladder. Surg Gynecol Obstet 138:97-108, 1974[Medline]

6. Braver DJ, Modan M, Chetrit A, et al: Drinking, micturition habits, and urine concentration as potential risk factors in urinary bladder cancer. J Natl Cancer Inst 78:437-440, 1987

7. Kadlubar FF, Dooley KL, Teitel CH, et al: Frequency of urination and its effects on metabolism, pharmacokinetics, blood hemoglobin adduct formation, and liver and urinary bladder DNA adduct levels in beagle dogs given the carcinogen 4-aminobiphenyl. Cancer Res 51:4371-4377, 1991[Abstract/Free Full Text]

8. Shannon J, White E, Shattuck AL, et al: Relationship of food groups and water intake to colon cancer risk. Cancer Epidemiol Biomarkers Prev 5:495-502, 1996[Medline]

9. Tang R, Wang JY, Lo SK, et al: Physical activity, water intake, and risk of colorectal cancer in Taiwan: A hospital-based case-control study. Int J Cancer 82:484-489, 1999[CrossRef][Medline]

10. Uccheddu A, Murgia C, Licheri S, et al: The incidence of 1, 2-dimethylhydrazine-induced colonic neoplasms in the rat: The effect of constipation. G Chir 12:572-574, 1991[Medline]

11. Stookey JD, Belderson PE, Russell JM, et al: Correspondence re: J. Shannon et al, Relationship of food groups and water intake to colon cancer risk. Cancer Epidemiol, Biomarkers & Prev., 5:495-502. Cancer Epidemiol Biomarkers Prev 6:657-658, 1997[Medline]

12. Hohenegger M, Laminger U, Om P, et al: Metabolic effects of water deprivation. J Clin Chem Clin Biochem 24:277-282, 1986[Medline]

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