Although the thermolabile MTHFR mutation is very common, it does not appear to be a significant genetic risk factor for typical late-onset vascular disease. Because MTHFR homozygotes have increased homocysteine with low folate levels, this mutation may contribute to early-onset or familial vascular disease. The genotype dependence of the folate-homocysteine correlation further suggests that homozygotes for this mutation may have both an exaggerated hyperhomocysteinemic response to folic acid depletion and a better response to folic acid therapy.
Objective To assess whether genetic polymorphisms implicated as risk factors for other tobacco‐associated malignancies are associated with altered risk of head and neck squamous cell carcinoma. Design Case‐control study. Subjects One hundred sixty patients with head and neck squamous cell carcinoma recruited from a university‐based head and neck oncology clinic and 149 population‐based controls. Methods Genotyping of the CYP1A1 (Ile462Val), GSTM1 (null), GSTP1 (Ile105Val), GSTT1 (null), and P53 (Arg72Pro) genes was performed by polymerase chain reaction–based techniques on DNA prepared from peripheral blood. In addition, a questionnaire was used to collect demographic information from each subject. Results Cases were significantly older (p < .0001) and had significantly greater tobacco use (p < .0001) and were more likely to be male (p < .0001) than were control subjects, thus confirming known risk factors for this disease. When cases and controls were compared by simple chi‐square analysis, only the frequency of CYP1A1 (Ile462Val) polymorphism was significantly different between cases and controls (OR = .42; 95% CI = .18–.99; p < .04). However, with a logistic regression model to control for known risk factors, we were unable to demonstrate a significant association with head and neck cancer for any of the polymorphisms tested, including CYP1A1. Conclusions This population fails to identify a relationship between the above‐mentioned polymorphisms and head and neck cancer. © 2000 John Wiley & Sons, Inc. Head Neck 22: 609–617, 2000.
Background. Glutathione S-transferase T1 detoxifies some environmental carcinogens while activating others and is deleted in 15% to 38% of humans. We sought to determine whether GSTT1 genotype and genotypes of several related genes are associated with risk of squamous cell carcinoma of the head and neck (HNSCC).Methods. Somatic genotypes for GSTT1, GSTM1, GSTP1, and CYP1A1 were determined in 283 individuals with HNSCC and 208 population-based controls.Results. The OR for presence of GSTT1 was 1.6 (CI, 1.1 -2.5, p = .03). HNSCC risk was not associated with GSTM1 null genotype, the presence of the GSTP1 Val/Val genotype, or the Val/Val homozygous genotype for CYP1A1. Stratified analysis revealed disparate ORs for women (OR, 3.0; CI, 1.5 -6.3) and men (OR, 1.2; CI, 0.7 -2.1) for the presence of GSTT1.Conclusions. In this population, the presence of GSTT1 gene was associated with a significant increase in the risk of HNSCC.This association was particularly robust in women. B
Glutathione S-transferase P1 (GSTP1) is markedly downregulated in prostate cancer and prostatic intraepithelial neoplasia compared to normal prostate tissue. Downregulation of GSTP1 may, therefore, be an early event in prostate carcinogenesis. An A?G polymorphism at nucleotide 313 results in an amino acid substitution (Ile105Val) in the substrate binding site of GSTP1 and reduces catalytic activity of GSTP1. In a study of 36 prostate cancer patients, Harries et al. reported that the Ile/Ile genotype is associated with a decreased risk of prostate cancer (odds ratio 0.4 (0.17 -0.82)). We sought to confirm this finding and to examine the impact of this polymorphism together with several related polymorphisms implicated as risk factors for carcinogen-associated malignancies. One hundred and seventeen patients with prostate adenocarcinoma and 183 population-based controls were recruited to this case -control study. Genotyping of the GSTP1 (Ile105Val), GSTM1 (null), GSTT1 (null) and CYP1A1 (Ile462Val) genes was performed using polymerase chain reaction (PCR) based techniques on DNA prepared from peripheral blood. A questionnaire was used to collect demographic information from each subject. Cases were significantly older (P < 0.0001) and had significantly greater family history of prostate cancer (P < 0.0001), confirming known risk factors for this disease. By w 2 analysis, none of the genotype distributions varied among cases and controls. Using a logistic regression model to control for known risk factors we were also unable to demonstrate a significant association with prostate cancer for any of the polymorphisms tested. This population fails to identify a relationship between the above polymorphisms and prostate adenocarcinoma.
A 74 year old white man entered the Union Printers' Hospital in April, 1948. He complained of weakness and severe shortness of breath which were present even at rest. These symptoms first appeared approximately one year previously and had become progressively severe. The patient also had a slight cough for many .years which he attributed to smoking; the cough was nonproductive and its character had not changed. There was no history of hemoptysis, wheezing, chest pain or weight loss. One and one-half years prior to admission, he had suffered a "stroke" with partial paralysis in the muscles of the right side of the body. The functioning of the extremities of the right side had greatly improved in the meantime. The patient's past health had been otherwise good and there were no other significant facts in the history which were related to his present illness.His memory for past events was poor. Ophthalmoscopic examination showed a small area of central chorio-retinitis, and narrow tortuous retinal arterioles. Percussion of the chest was hyper-resonant and the breath sounds were diminished. The blood pressure was 135/70. No other significant physical findings were noted.Anteroposterior and lateral roentgenograms of the chest on April 5, 194S showed a discrete, oval, tumor mass, S.O cm. in diameter, in the region of the right hilus. The intercostal spaces on the right appeared slightly narrower than normal (Fig. 1). X-ray examination of the skull showed no evidence of metastatic involvement. Laboratory studies revealed sputum, negative for acid-fast bacilli; urinalysis, normal; blood, erythrocytes 3,270,000; hemoglobin, 13.5 grams; leukocytes, 9350 with a normal differential count; hematocrit reading, 30 per cent; sedimentation rate, 33 mm. in 1 hour; blood nonprotein nitrogen, 41.5 mg.; Kahn, negative. On bronchoscopic examination, performed on April 13, 1948, the carina was in the midline, enlarged, and its motions were restricted; a nodular tumor mass was present in the right main bronchus near the orifice of the middle lobe; there was no significant degree of bronchial obstruction. Biopsy showed the lesion to be a bronchial adenoma.Since both the bronchoscopic examination and the patient's clinical condition suggested the likelihood of metastatic bronchogenic carcinoma, it was elected to follow a course of palliative treatment. Roentgenogram of the chest on July 7, 1948, showed no increase in the size of the tumor mass. The clinical condition gradually became worse and the patient expired on December 1, 1948, approximately eight months after admission. Pathologic DataGross findings. The right lung weighed 870 grams and showed some obliteration of the interlobar fissures by fibrous adhesions. The lung contained a discrete,
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