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Biomedical subjects

J Boreham

Publications and source records attributed to J Boreham.

At least 37 records · Page 2Linked to original sources

Serum vitamin E and subsequent risk of cancer.

In a prospective study of about 22,000 men attending a screening centre, serum samples were collected and stored. The concentration of vitamin E (alpha-tocopherol) was measured in the stored serum samples from 271 men subsequently notified as having cancer and from 533 unaffected controls, matched for age, smoking history and duration of storage of the serum samples. The mean vitamin E level of the cancer subjects was not significantly different from that of their matched controls. The mean level in the cancer subjects who were diagnosed as having cancer before the elapse of one year from the date of blood collection was, however, significantly lower than the mean concentration of their matched controls (10.0 and 11.5 mgl-1 respectively, P = 0.003). For subjects whose cancers were diagnosed one or more years after blood collection the difference was not statistically significant either for all cancers or for cancers of six sites considered separately, viz. lung, colon and rectum, stomach, bladder, central nervous system and skin. The most likely explanation for these results is that the low vitamin E levels observed in these subjects were a metabolic consequence, rather than a precursor, of the cancer. This would explain, at least in part, the overall inverse association between serum vitamin E and risk of cancer observed in the published epidemiological studies on serum vitamin E and cancer.

Adult↗

Serum retinol and subsequent risk of cancer.

In a prospective study of about 22,000 men attending a well person screening centre, serum samples were collected and stored. The concentration of retinol was measured in the stored serum samples from 227 men subsequently notified as having cancer and from 454 unaffected controls, matched for age, smoking history and duration of storage of the serum samples. The mean serum retinol concentration of the cancer subjects who developed cancer before the elapse of one year since the time blood was collected was significantly lower than the mean concentration of their matched controls (641 and 722 micrograms l-1 respectively, P less than 0.001). For subjects whose cancer developed one to two years after blood had been collected, the difference was less (650 and 701 micrograms l-1 respectively, P less than 0.01). For subjects whose cancer developed three or more years after blood was collected, the mean retinol level was higher than in their controls, although not statistically significantly so (694 and 663 micrograms l-1 respectively). These findings suggest that the inverse association between serum retinol and risk of cancer that was previously observed was due to low serum retinol being a metabolic consequence of cancer rather than a precursor of cancer.

Disease Susceptibility↗

Plasma retinol, beta-carotene and vitamin E levels in relation to the future risk of breast cancer.

In a prospective study of 5,004 women in Guernsey, plasma samples were collected and stored. Retinol, beta-carotene and vitamin E levels were later measured in the samples from 39 women who subsequently developed breast cancer and from 78 controls who did not develop cancer. Plasma retinol levels were not related to the risk of breast cancer, mean levels among cases and controls being 485 micrograms l-1 and 479 micrograms l-1 respectively. Plasma vitamin E levels showed a clear association, low levels being associated with a significantly higher risk of cancer. The mean vitamin E levels among cases and controls were 4.7 mg l-1 and 6.0 mg l-1 respectively (P less than 0.025), and the risk of breast cancer in women with vitamin E levels in the lowest quintile was about 5-times higher than the risk for women with levels in the highest quintile (P less than 0.01). beta-carotene levels showed a tendency to be lower in women who developed cancer than in controls (36 micrograms l-1 among cases compared with 50 micrograms l-1 among controls) but the difference was not statistically significant.

Adult↗

Occupational exposure to hydrazine and subsequent risk of cancer.

Four hundred and twenty seven men with varying degrees of occupational exposure to hydrazine, a weak animal carcinogen, were studied to see if they provided any evidence of carcinogenicity to man. The observed mortality was close to that expected for lung cancer, other cancers, and all other causes, irrespective of the level of exposure. There were 49 deaths (61.47 expected) from all causes including five deaths from lung cancer (6.65 expected). The results show that no obvious hazards associated with hydrazine exposure have yet appeared but because of the small number of men studied they can only exclude gross hazards.

Chemical Industry↗

Relative intakes of tar, nicotine, and carbon monoxide from cigarettes of different yields.

The relative intakes of tar, nicotine, and carbon monoxide were estimated in 2455 cigarette smokers, who freely smoked their usual brands of cigarette. The estimates were derived by using an objective index of inhaling based on the measurement of carboxyhaemoglobin divided by the carbon monoxide yield of the cigarettes smoked, after background and carry over carboxyhaemoglobin effects had been allowed for. Separate analyses were performed according to the yield and type (plain, filter, etc) of cigarette smoked. The analyses based on yield indicated that the extent of inhaling was adjusted sufficiently to achieve similar intakes of nicotine/carbon monoxide regardless of the nicotine/carbon monoxide yield. It was not, however, sufficiently increased to achieve a similar intake of tar as the tar yield of the cigarette decreased. The analyses based on type of cigarette indicated that the extent of inhaling was adjusted to achieve similar intakes of tar and nicotine regardless of the type of cigarette smoked, but that this led to a greater intake of carbon monoxide among filter cigarette smokers than that among smokers of plain cigarettes--more so than would have been expected from their relative carbon monoxide yields. Two conclusions arise from these results. Firstly, any harmful effects of nicotine/carbon monoxide are unlikely to be materially reduced by smoking cigarettes with lower yields of nicotine/carbon monoxide, but the harmful effects of tar are likely to be reduced by smoking cigarettes with lower tar yields. These predictions appear to be borne out by epidemiological observations. Secondly, any harmful effects of carbon monoxide on the cardiovascular system will be greater in smokers of modern filter cigarettes than in smokers of modern plain cigarettes, provided that these two groups of smokers are otherwise similar with respect to risk of cardiovascular disease.

Adult↗

Urinary nicotine concentrations in cigarette and pipe smokers.

Urinary concentrations of nicotine were studied in men who did not smoke (27) and in men who smoked cigarettes only (145) or pipes only (48). The median urinary nicotine concentrations were less than 50 ng/ml (the detection limit of the assay for urine tests) in the non-smokers, 1393 ng/ml in the cigarette smokers, and 1048 ng/ml in the pipe smokers. These values were standardised for urinary pH and creatinine concentration to allow for the fact that nicotine excretion is influenced by the acidity of the urine and by urinary flow rate. The high urinary nicotine concentrations in the pipe and cigarette smokers indicated that both types of smoker have relatively high systemic nicotine concentrations. This observation, together with the fact that large prospective studies have shown that pipe smokers have no material excess risk of coronary heart disease whereas cigarette smokers do, provides evidence that nicotine is unlikely to be the major cause of the excess deaths from coronary heart disease in cigarette smokers. This conclusion is consistent with earlier observations based on serum cotinine concentrations in smokers and non-smokers.

Creatinine↗

Alpha-fetoprotein screening for open spina bifida: effect of routine biparietal diameter measurement to estimate gestational age.

The estimation of gestational age by "dates" (time since the first day of the last menstrual period) and by means of an ultrasound scan examination (measurement of fetal biparietal diameter) lead to different results when screening for open spina bifida by maternal serum alphafetoprotein (A.F.P.) measurement. This paper provides estimates of the detection rate for open spina bifida, the false positive rate, and the odds of being affected given a positive A.F.P. result when gestational age is estimated according to the two methods. Estimates are also given on the odds of being affected for individuals with a particular serum A.F.P. result. The estimates may be useful to those concerned with the development and design of screening programmes for open spina bifida as well as to clinicians concerned with providing risk estimates for individual patients.

Adult↗

Inhaling and lung cancer: an anomaly explained.

An objective index of inhaling cigarette smoke based on carboxyhaemoglobin concentrations and the carbon monoxide yields of cigarettes was used to investigate possible systematic differences in the extent of inhaling among light and heavy smokers when classified according to their self described inhaling habits. A total of 2108 men who smoked cigarettes were studied. Heavy smokers (20 or more cigarettes a day) had a higher average inhaling index than light smokers (fewer than 20 cigarettes a day) both among those who said that they inhaled and among those who said that they did not. This observation, together with indirect evidence that heavy smokers who inhale deeply may to some extent avoid depositing smoke condensate on their main bronchial epithelium, explains a hitherto unresolved anomaly--namely, that the risk of lung cancer is less among heavy cigarette smokers who say that they inhale than it is among those who say that they do not inhale.

Adult↗

Maternal serum alpha-fetoprotein and low birth weight in relation to gestational age.

To determine when in the first and second trimester a raised serum alpha-fetoprotein (AFP) level best predicts low birth weight a case-control study was performed on 157 singleton low birth-weight (less than or equal to 2.5 kg) and 314 singleton control pregnancies (birth weight greater than 2.5 kg). The association between raised maternal serum AFP and low birth weight was confirmed, but there was no special time in pregnancy before 29 weeks gestation when a raised AFP level predicted low birth weight materially better than at any other time.

Female↗

Effect of estimating gestational age by ultrasound cephalometry on the specificity of alpha-fetoprotein screening for open neural-tube defects.

A total of 1268 women had a maternal serum alpha-fetoprotein (AFP) screening test for open neural-tube defects between 15 and 22 weeks gestation and a routine ultrasound examination at their first antenatal visit. All had a singleton infant without a neural-tube defect. AFP values were expressed as multiples of the normal median at the relevant gestational age (MoM). The percentage of women with raised maternal serum AFP levels was less when gestation was estimated by the fetal biparietal diameter (BPD) than when the time since the first day of the last menstrual period (LMP) was used; 1.8% compared with 2.3% at a serum AFP cut-off level of 2.5 MoM. Different ultrasound policies were compared for their effect on AFP screening and the best was found to be routine BPD measurement used together with a higher cut-off level than usual. For example, using a cut-off level of 3.0 MoM the detection rate for open spina bifida at 16-18 weeks gestation would be about 88% and the proportion of unaffected singleton pregnancies with raised levels only 0.9%. These results are materially better than those achieved by a policy of scanning only those women with a raised AFP level (79% and 1.4% respectively with a more conventional cut-off level of 2.5 MoM) or, in addition, scanning those with doubtful gestational ages (82% and 1.7% respectively with a cut-off level of 2.5 MoM).

Cephalometry↗

Serum cotinine levels in pipe smokers: evidence against nicotine as cause of coronary heart disease.

Serum levels of cotinine (a principal metabolite of nicotine) were studied in men who did not smoke (28), and in men who smoked cigarettes only (150), cigars only (70), and pipes only (56). The mean cotinine level for pipe smokers was 389 ng/ml, significantly higher than the mean level for cigarette and cigar smokers (306 and 121 ng/ml, respectively); no cotinine was detected in the serum from any of the non-smokers. Large prospective studies have shown that pipe smokers have no material excess risk of coronary heart disease but cigarette smokers do, so that our observations indicate that nicotine is unlikely to be the major cause of the excess coronary heart disease mortality in cigarette smokers.

Adult↗

The effect of maternal weight on maternal serum alpha-fetoprotein levels.

In 902 singleton pregnancies, maternal serum alpha-fetoprotein (AFP) levels between 15 and 20 weeks of pregnancy were significantly related to maternal weight (r = 0.24, p less than 0.0001). Lighter women had on average higher AFP levels than heavier women, perhaps on account of the greater concentration of AFP in their relatively smaller volume of blood. The mean AFP level for women weighing less than 45 kg was 68% higher than the mean level for women weighing 85 kg or more. Maternal weight was found to be an important factor which could account for false positive AFP results in antenatal screening for open neural tube defects. A policy of adjusting maternal serum AFP values according to maternal weight among women with borderline positive results could reduce the number having a diagnostic amniocentesis with only a negligible loss of detection for open spina bifida. With such a policy, using a cut-off level of 2.5 x normal median, the false positive rate in the 902 women screened would have been reduced fom 2.8% to 2.0%.

Body Weight↗

The importance of tar and nicotine in determining cigarette smoking habits.

Cigarette consumption and inhaling, assessed using carboxyhaemoglobin levels, were studied in 1786 men to investigate the importance of tar and nicotine as determinants of smoking habits. No prior warning was given that smoking habits would be studied. Neither nicotine nor tar yields materially influenced the number of cigarettes smoked a day. Both nicotine and tar yields were negatively associated with inhaling (p less than 0.001) but after allowing for either of the two yields the effect of the other on inhaling was no longer statistically significant. There was, therefore, no indication as to whether nicotine or tar was the more important determinant of smoking habit.

Carbon Monoxide↗

Carbon monoxide in breath in relation to smoking and carboxyhaemoglobin levels.

Carboxyhaemoglobin (COHb) levels were studied in 11 249 men. The distribution among the 2613 men who smoked cigarettes was well separated from that in 6641 non-smokers (including ex-smokers). The distribution for 2005 cigar and pipe smokers was intermediate, though some of the highest COHb levels occurred in cigar smokers. Using a COHb cut-off level of 2%, 81% of cigarette smokers, 35% of cigar and pipe smokers, and 1.0% of non-smokers had raised COHb levels. In a subsidiary experiment alveolar air samples were collected from 162 smokers and 25 non-smokers using a simple breath sampling technique. Carbon monoxide concentrations in alveolar breath were highly correlated with COHb levels (r = 0.97) indicating that COHb levels can be estimated reliably by measuring the concentration of carbon monoxide in breath. Alveolar carbon monoxide measurement is thus a simple method of estimating whether a person is likely to be a smoker.

Adult↗

Low serum-vitamin-A and subsequent risk of cancer. Preliminary results of a prospective study.

In a prospective study of about 16 000 men, serum samples were collected and stored. Vitamin-A (retinol) levels were later measured in the stored samples from the 86 men who were subsequently notified as having developed cancer and in the stored samples from 172 controls who did not develop cancer. Low retinol levels were associated with an increased risk of cancer. The association was independent of age, smoking habits, and serum-cholesterol level aand was greatest for men who developed lung cancer (mean retinol level 187 i.u./dl compared with 229 i.u./dl for the controls, p < 0.005). The risk of cancer at any site for men with retinol levels in the lowest quintile was 2.2 times greater than the risk for men with levels in the highest quintile (p < 0.025). These results suggest that measures taken to increase serum-retinol levels in man may lead to a reduction in cancer risk.

Adult↗