In soil, fertilizers containing inorganic nitrogen and wastes containing organic nitrogen are first decomposed to give ammonia, which is then oxidized to nitrite and nitrate. The nitrate is taken up by plants during their growth and used in the synthesis of organic nitrogenous compounds. Surplus nitrate readily moves with groundwater (2, 3). Under aerobic conditions, it percolates in large quantities into the aquifer because of the small extent to which degradation or denitrification occurs. Under anaerobic conditions, nitrate may be denitrified or degraded almost completely to nitrogen. The presence of high or low water tables, the amount of rainwater, the presence of other organic material, and other physicochemical properties are also important in determining the fate of nitrate in soil ( 4). In surface water, nitrification and denitrification may also occur, depending on the temperature and pH. The uptake of nitrate by plants, however, is responsible for most of the nitrate reduction in surface water. Nitrogen compounds are formed in the air by lightning or discharged into it from industrial processes, motor vehicles, and intensive agriculture. Nitrate is present in air primarily as nitric acid and inorganic aerosols, as well as nitrate radicals and organic gases or aerosols. These are removed by wet and dry deposition.

WHO guidelines for drinking-water quality.

Pancreatic cancer is the eighth major form of cancer-related death worldwide, causing 227 000 deaths annually. Type-II diabetes is widely considered to be associated with pancreatic cancer, but whether this represents a causal or consequential association is unclear. We conducted a meta-analysis to examine this association. A computer-based literature search from 1966 to 2005 yielded 17 case–control and 19 cohort or nested case–control studies with information on 9220 individuals with pancreatic cancer. The age and sex-adjusted odds ratio (OR) for pancreatic cancer associated with type-II diabetes was obtained from each study. The combined summary odds ratio was 1.82 (95% confidence interval (95% CI) 1.66–1.89), with evidence of heterogeneity across the studies (P=0.002 for case–control and P=0.05 for cohort studies) that was explained, in part, by higher risks being reported by smaller studies and studies that reported before 2000. Individuals in whom diabetes had only recently been diagnosed (<4 years) had a 50% greater risk of the malignancy compared with individuals who had diabetes for ⩾5 years (OR 2.1 vs 1.5; P=0.005). These results support a modest causal association between type-II diabetes and pancreatic cancer.

/pdf/type-ii-diabetes-and-pancreatic-cancer-a-meta-analysis-of-36-4tc1yt9nyc.pdf

Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies.

Objective. —To evaluate diabetes mellitus as a risk factor for pancreatic cancer with the consideration that diabetes may also be a consequence of pancreatic cancer. Data Sources. —Pertinent studies of diabetes mellitus and pancreatic cancer published between 1975 and 1994 were identified from a MEDLINE search and from citations in articles and books. Study Selection. —Twenty of a total of 30 case-control and cohort studies met the two inclusion criteria: cases with a duration of diabetes of at least 1 year prior to either pancreatic cancer diagnosis or death and the ability to calculate an appropriate relative risk (RR) estimate and variance. Data Extraction and Synthesis. —The pooled RR and 95% confidence interval (CI) of pancreatic cancer for diabetics relative to nondiabetics was 2.1 (1.6 to 2.8). There was a tendency for a higher RR for the nine cohort studies (RR, 2.6; 95% CI, 1.6 to 4.1) than for the 11 case-control studies (RR, 1.8; 95% CI, 1.1 to 2.7). Requiring diabetes duration of at least 5 years resulted in an RR of 2.0 (95% CI, 1.2 to 3.2). Conclusion. —Pancreatic cancer occurs with increased frequency among persons with long-standing diabetes. ( JAMA . 1995;273:1605-1609)

Diabetes Mellitus as a Risk Factor for Pancreatic Cancer: A Meta-analysis

Acute pancreatitis, chronic pancreatitis and pancreatic cancer are responsible for most of the burden of exocrine pancreatic disease. Glandular damage from recurrent bouts of acute pancreatitis can lead to irreversible changes characteristic of chronic pancreatitis. In recent decades accumulating evidence has defined longstanding pre-existing chronic pancreatitis as a strong risk factor for pancreatic cancer. The lag period between diagnosis of chronic pancreatitis and pancreatic cancer is usually one or two decades: pancreatitis appearing a year or two before the diagnosis of pancreatic cancer is often the result of tumour-related ductal obstruction. The risk of developing pancreatic cancer appears to be highest in rare types of pancreatitis with an early onset, such as hereditary pancreatitis and tropical pancreatitis. Even though there is a strong link between chronic pancreatitis and pancreatic cancer, over a 20 year period only around five percent of patients with chronic pancreatitis will develop pancreatic cancer. Until the development of more sophisticated screening procedures, screening is not recommended for patients with chronic pancreatitis.

Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection

In the United States the incidence of and mortality from pancreatic cancer have increased over the past several decades but have tended to level off in recent years. The rates are higher in blacks than in whites and higher in males than in females. Mortality rates increase with age but there appears to be a decline in elderly blacks, possibly on an artifactual basis. There is a suggestion that rates are higher in Jews. No consistent differences by socioeconomic status or by geographic location within the United States have been identified. Both genetic and environmental factors may be playing significant roles in this disease. Cigarette smoking may be etiologically related, or at the very least, may help to identify a group of patients at increased risk of pancreatic cancer. However, the relative risk estimated for cigarette smoking is much lower than that found for cancer of the lung. The leveling off in incidence and mortality rates for pancreatic cancer in recent years also differs from the time trends observed for lung cancer. However, this could result from differences in site-specific carcinogens and from the fact that the lung is the first organ to be exposed to cigarette smoke in the highest concentrations and prior to the metabolism of any of its components. 
Dietary factors may have an important role in pancreatic cancer, but further research is needed to clarify this relationship. In particular, the possibility that dietary fats may be implicated and that vitamins or fiber may be protective in this disease remains to be explored. Finally, there is suggestive evidence that specific chemical exposures may be carcinogenic for the pancreas. Many of the data are from animal studies, and the findings from human studies are not entirely consistent.

Epidemiology of Pancreatic Cancer

In the past 30 years, the incidence of pancreatic cancer has increased substantially. The disease now causes more deaths than all other malignant neoplasms, except those of the colorectal region, lung, and breast. A study in over 115 hospitals in five metropolitan areas showed that males with pancreatic cancer were more often employed in the dry cleaning business or in occupations involving close exposure to gasoline, increasing the risk for pancreatic cancer up to five times. Females at risk for pancreatic cancer were more likely to smoke cigarettes, to have uterine myomas, and to have undergone oophorectomy or spontaneous abortions. Generally, these patients were of higher social class and drank more wine and decaffeinated coffee than demographically similar controls. Assessment of the effects of several factors showed that relative risks increased 34-fold among females and nearly sixfold among males. While no single factor accounts for the preponderance of pancreatic cancer, a combination of factors—each associated with a relatively small risk enhancement—may very well do so. (JAMA1981;245:147-152)

A multifactorial model for pancreatic cancer in man. Epidemiologic evidence

An epidemiologic study designed to elucidate the possible roles of the artificial sweeteners saccharin and cyclamate in human urinary bladder cancer was recently completed. The previous intake of each of these substances among 519 patients with histopathologically confirmed bladder cancer and an equal number of matching controls in metropolitan Baltimore did not differ significantly in frequency, quantity, or duration. These normal findings persisted after simultaneous adjustment for the effects of smoking, occupation, age, diabetes mellitus, and a number of other potentially confounding factors. They are substantiated by the failure of the relative risk of bladder cancer to increase with increasing exposure to artificial sweeteners. It is concluded that neither saccharin nor cyclamate is likely to be carcinogenic in man, at least at the moderate dietary ingestion levels reported by the patient sample. (JAMA240:349-355, 1978)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=360615&pdfFileName=jama_240_4_017.pdf

Saccharin, Cyclamate, and Human Bladder Cancer: No Evidence of an Association

In Reply.— Although secular changes in the incidence of cancer are often difficult to document in view of the paucity of relevant statistics, the available data suggest that pancreatic cancer increased rather steadily between the second and sixth decades of this century. Using US mortality data, Devesa and Silverman 1 observed substantial increases in pancreatic cancer death rates among both whites and nonwhites between 1935 and 1971. Krain 2 calculated a threefold increase in pancreatic cancer mortality between 1920 and 1965 in the United States and a number of other countries. Data as yet unpublished from the vital records of the state of Maryland indicate that the death rate from pancreatic cancer among our citizens increased during the interval between 1965 and 1979. A comparison of statistics derived from the second and third National Cancer Surveys also disclosed increases in the incidence of pancreatic cancer among males and females of

Incidence of Pancreatic Cancer-Reply

It is unlikely that many readers ofThe Journal"have been misled by the last sentence" of our abstract, if only because quantitative risk estimates are presented in the text of our article. In any event, Professor Gryder also seems to acknowledge that "quantitative estimates of the magnitude of an increased risk are, of course, for ideal situations that can be approximated only in a real experiment." The concerned physician or lay person may well ponder which is the more relevant: idealized quantitative estimates of cancer risk or etiologic inferences based on biologic reasoning—a knowledge of the cancer process and statistical analysis? We agree with Gryder that "the animal-feeding experiments cannot be ignored." However, the three cited animal studies pose serious inferential problems to the cancer experimentalist.1For example, the Canadian rat study was designed to assess the carcinogenicity of orthotoluene-sulfonamide rather than saccharin; accordingly, only one

Irving I. Kessler

Papers

A multifactorial model for pancreatic cancer in man. Epidemiologic evidence

Saccharin, Cyclamate, and Human Bladder Cancer: No Evidence of an Association

Incidence of Pancreatic Cancer-Reply

Saccharin and Bladder Cancer-Reply