Cytochrome P450IIE1 is responsible for the activation of carcinogenic N-nitrosamines, benzene, urethane, and other low-molecular-weight compounds. Restriction fragment length polymorphisms (PstI and RsaI restriction enzymes) have been identified in the cytochrome P450IIE1 transcription regulatory region that may affect expression. This study describes the PstI and RsaI polymorphisms in different racial populations and in a case-control study of lung cancer. The allelic frequencies were markedly different in Japanese, African-Americans, and Caucasians: the PstI rare allele was present at a frequency of 2% in Caucasians, 5% in African-Americans, and 24% in Japanese (P < 0.05). For the RsaI rare allele, frequencies were 2% in Caucasians, 2% in African-Americans, and 27% in Japanese (P < 0.05). The assay was also applied to 128 individuals enrolled in a case-control study of lung cancer. Although limited in statistical power, the data indicate no evidence for an association in the aggregate of cytochrome P450IIE1 PstI [for which the odds ratio was 0.7 (95% confidence interval (C.I.) = 0.2-2.8)] or RsaI [for which the odds ratio was 0.9 (95% C.I. = 0.2-5.4)] restriction fragment length polymorphisms with lung cancer in this U.S. population. When analyzed by race, the lung cancer odds ratio for the PstI mutant allele in African-Americans was 0.19 (95% C.I. = 0.03-1.38), and in Caucasians it was 4.13 (95% C.I. = 0.34-48.8). For the RsaI mutant allele, the odds ratios were 0.20 (95% C.I. = 0.02-2.43) and 4.28 (95% C.I. = 0.35-50.6), respectively. The ethnic differences of these restriction fragment length polymorphisms might be related to genetic susceptibilities for lung cancer among Caucasians and for gastric or esophageal cancer among Japanese.

/pdf/cytochrome-p450iie1-genetic-polymorphisms-racial-variation-3btygu5ry0.pdf

Cytochrome P450IIE1 genetic polymorphisms, racial variation, and lung cancer risk.

Pickled vegetables in the aetiology of oesophageal cancer in Hong Kong Chinese.

Epidemiologic evidence on the relation between nutrition and esophageal cancer is reviewed. Results from ecologic, case-control, cohort, and intervention studies are included. Most of the findings pertain more to squamous cell carcinoma than adenocarcinoma of the esophagus. The protective effect of fruit and vegetable consumption is supported by a large body of evidence, especially from case-control studies. The effects of food groups and nutrients other than fruits and vegetables also have been examined, but the overall evidence is less convincing. Recent intervention studies in high incidence areas in China indicate that micronutrient supplements may have a modest effect in reducing risk, but the generalizability of this result is uncertain. Hot drinks are likelyto increase the risk of esophageal cancer. On the other hand, the role of tea drinking, especially the use of green tea, remains to be defined better.

Nutrition and esophageal cancer.

Two sensitive procedures to quantitate human exposure to endogenous N-nitroso compounds (NOC) and/or methylating agents have been developed. One, the NPRO test, is based on the excretion of N-nitrosoproline (NPRO) and other N-nitrosoamino acids in the urine, that are measured as an index of endogenous nitrosation, following ingestion of precursors. The NPRO test has been applied to human subjects in clinical and epidemiological studies, and the kinetics and dietary modifiers of endogenous nitrosation have been investigated. Results obtained after application of the NPRO test to subjects at high risk for cancers of the stomach, esophagus, oral cavity and urinary bladder are summarized. In most instances, higher exposures to endogenous NOC were found in high-risk subjects, but individual exposure was greatly affected by dietary modifiers or disease state. Vitamin C efficiently lowered the body burden of intragastrically formed NOC. In experimental animals 3-methyladenine (3-MeAde) is excreted in urine following exposure to methylating NOC. Humans normally excrete 3-MeAde, the origin of which remains unknown. Recently developed analytical methodology permits large numbers of human urine samples to be analyzed and a wide variation is observed. Preliminary results suggest a weak correlation between basal NPRO excretion and background 3-MeAde excretion. Taken together, the results point to an etiological role of endogenously formed NOC in certain human cancers, and provide an interpretation of epidemiological findings that have shown protective effects of fruits and vegetables against several malignancies.

Exposure of humans to endogenous N-nitroso compounds: implications in cancer etiology.

Overnight urine samples were collected from approximately 60 male adults in each of 69 counties of China in 1989. Two specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids and nitrate were measured in urine samples and correlated with cumulative mortality rates for subjects aged between 0 and 64 years in the 1970s. Oesophageal cancer mortality rates were positively and significantly associated with (i) urinary levels of excreted N-nitrosoproline (NPRO) (after proline and ascorbic acid loading or proline loading only), (ii) N-nitrososarcosine levels, and (iii) nitrosation potential (the decrease in the amount of urinary NPRO after adding ascorbic acid to the proline load). There were also positive correlations between the urinary level of NPRO or other N-nitrosamino acids and that of nitrate. The urinary excretion of nitrate was associated with consumption of various nitrate-rich vegetables. The results suggest that N-nitroso compounds (NOC) or other nitrite-derived carcinogens are implicated in the aetiology of oesophageal cancer in China.

Geographic association between urinary excretion of N‐nitroso compounds and oesophageal cancer mortality in china

Samples of 12-h overnight urine were collected from approximately 40 male adults in each of the 26 counties of China. Two urine specimens were collected from each subject--one after a loading dose of proline and ascorbic acid and another after a loading dose of proline only. Levels of N-nitrosamino acids, nitrite and nitrate were measured in urine samples and correlated with cancer mortality per 100,000 male subjects in the truncated age range 35-64 years. Preliminary results show no clear correlation between presence of stomach cancer or liver cancer and nitrosation potential [as measured by the urinary level of N-nitrosoproline (NPRO) after the proline load test or of nitrate]. There was a moderate, although not clearly significant, tendency for oesophageal cancer mortality rates to be associated positively with nitrosation potential and negatively with background ascorbate levels in plasma. This result was due chiefly to the inclusion of one county (Song Xian) in which there is a fairly high oesophageal mortality rate, an average nitrosation potential three times greater than that of any other county, and the lowest ascorbate index of any county. Further study of this county is planned.

A correlation study on urinary excretion of N-nitroso compounds and cancer mortality in China: interim results.

Prior to the superconducting transition at ${T}_{\mathrm{c}}\ensuremath{\approx}1.5\phantom{\rule{0.28em}{0ex}}\mathrm{K}$, the pyrite-type ${\mathrm{CuS}}_{2}$ undergoes a charge-density-wave (CDW) transition at ${T}_{\mathrm{s}}\ensuremath{\approx}150\phantom{\rule{0.28em}{0ex}}\mathrm{K}$ at ambient pressure. Here we studied the interplay between CDW and superconductivity (SC) in ${\mathrm{CuS}}_{2}$ by tracking their evolutions with pressure via detailed measurements of resistivity and magnetic susceptibility under hydrostatic pressures up to 6.6 GPa. The high-quality ${\mathrm{CuS}}_{2}$ samples used in the present study were synthesized under high-pressure and high-temperature conditions, and the formation of the $2\ifmmode\times\else\texttimes\fi{}2\ifmmode\times\else\texttimes\fi{}2$ supercell associated with the commensurate CDW order below ${T}_{\mathrm{s}}$ was confirmed by low-temperature transmission electron microscope. Our high-pressure results uncover a pressure-driven superconducting dome with an enhanced ${{T}_{\mathrm{c}}}^{max}\ensuremath{\sim}2.3\phantom{\rule{0.28em}{0ex}}\mathrm{K}$ at $\ensuremath{\sim}1.8\phantom{\rule{0.28em}{0ex}}\mathrm{GPa}$ accompanying the gradual suppression of the CDW order. This work thus demonstrates the competing nature between CDW and SC in the pyrite-type superconductor ${\mathrm{CuS}}_{2}$. 

Pressure-driven superconducting dome in the vicinity of CDW in the pyrite-type superconductor 
CuS2

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A correlation study on urinary excretion of N-nitroso compounds and cancer mortality in China: interim results.

Pressure-driven superconducting dome in the vicinity of CDW in the pyrite-type superconductor CuS2