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H Vainio

Publications and source records attributed to H Vainio.

At least 37 records · Page 2Linked to original sources
PubMed2001

Use of biomarkers in risk assessment.

The systematic development and application of biomarkers in environmental health risk assessment is a relatively new field. At first, the major interest was in biomarkers of exposure, borrowing concepts from pharmacology, then it moved from the external estimates of exposure to internal measures of dose, and ultimately, to markers of target dose. While these markers provide evidence of exposures, they do not provide evidence of that toxicological damage has occurred. For this reason, measurements of DNA adducts and protein adducts are of interest, since they may provide bridges between exposures and disease end-points. In parallel, more quantitative and more sensitive end-points for diseases have been sought. Again, with advancing techniques in cytogenetics, extensive studies were conducted on such markers as chromosomal aberrations, micronuclei and other changes deemed to represent genomic damage. However, these types of end-points are quite unspecific for application to new hazards of uncertain human toxic (carcinogenic) potential. Recent work focusing on more specific early-effect markers such as certain oncogenes and tumour-suppressor genes have substantial promise as shown by work with aflatoxins and vinyl chloride. Such studies have also enhanced mechanistic insight. The advances in molecular genetics have led to an upsurge in interest in most susceptibility factors, and identification of polymorphisms of various enzymes has become possible. Ongoing search for "ultra-high risk" individuals may be fruitful, but probably only relevant to a small segment of potentially exposed populations. Factors associated with a small differential risk, however theoretically or mechanistically important, offer only little practical use.

Aflatoxins↗
PubMed2001

Glutathione S-transferase genotypes and allergic responses to diisocyanate exposure.

Diisocyanates are the most common low molecular weight chemicals to cause occupational asthma. However, only some 5-10% of exposed workers develop asthma, which suggests an underlying genetic susceptibility. Diisocyanates and their metabolites may be conjugated with glutathione by glutathione S-transferases (GSTs). We examined whether polymorphisms in the GSTM1, GSTM3, GSTP1 and GSTT1 genes modify allergic responses to diisocyanate exposure. The study population consisted of 182 diisocyanate exposed workers, 109 diagnosed with diisocyanate-induced asthma and 73 without asthma. Lack of the GSTM1 gene (null genotype) was associated with a 1.89-fold risk of diisocyanate-induced asthma [95% confidence interval (CI) 1.01-3.52]. Moreover, among the asthma patients, the GSTM1 null genotype was associated with lack of diisocyanate-specific immunoglobulin (Ig)E antibodies [odds ratio (OR) 0.18, 95% CI 0.05-0.61] and with late reaction in the specific bronchial provocation test (OR 2.82, 95% CI 1.15-6.88). Similarly, GSTM3 AA genotype was related to late reaction in the specific bronchial provocation test (OR 3.75, 95% CI 1.26-11.2). The GSTP1 Val/Val genotype, on the other hand, was related to high total IgE levels (OR 5.46, 95% CI 1.15-26.0). The most remarkable effect was seen for the combination of GSTM1 null and the GSTM3 AA genotype which was strongly associated with lack of diisocyanate-specific IgE antibodies (OR 0.09, 95% CI 0.01-0.73) and with late reaction in the bronchial provocation test (OR 11.0, 95% CI 2.19-55.3). The results suggest, for the first time, that the polymorphic GSTs, especially the mu class GSTs, play an important role in inception of ill effects related to occupational exposure to diisocyanates.

Adult↗
PubMed2001

Evaluation of cancer-preventive agents and strategies a new program at the International Agency for Research on Cancer.

About five years ago, the International Agency for Research on Cancer (IARC) initiated a new program, IARC Handbooks of Cancer Prevention, aimed at evaluating the evidence base for the cancer-preventive activity of various agents and strategies. To date (2001) 5 volumes have been published--1. Non-steroidalAnti-inflammatory Drugs, 2. Carotenoids, 3. Vitamin A, 4. Retinoids, and 5. Sunscreens--and volume 6 (Weight Control and Physical Activity) is in press. Future volumes will include evaluations of breast cancer screening (vol. 7) and fruits and vegetables (vol. 8).

Anticarcinogenic Agents↗
PubMed2001

Solvent use and time to pregnancy among female personnel in biomedical laboratories in Sweden.

OBJECTIVES: To elucidate possible effects on fecundability from chemical, biological, and physical agents in laboratories, a retrospective study based on a questionnaire was conducted among female personnel who worked in Swedish biomedical research laboratories. Female personnel in non-laboratory departments were used as a reference group. The maximum number of women included in the analyses was 560. This corresponded to 2519 menstrual cycles. These women had given birth at least once during the period 1990-4. METHODS: Time to pregnancy was used to estimate the fecundability-that is, probability of conception of a clinically detectable pregnancy per cycle. The fecundability ratio (FR) between exposed and unexposed cycles was calculated with a discrete time analogue of the Cox's proportional-hazards model. The FR estimates below unity indicate subfecundity. RESULTS: Work with organic solvents in general in laboratory work, gave a decreased adjusted fecundability ratio (FR) of 0.79 (95% confidence interval (95 % CI) 0.68 to 0.93). Moreover, work with acetone and use of viruses also showed decreased FRs, 0.72 (0.53 to 0.97) and 0.66 (0.49 to 0.90), respectively. CONCLUSIONS: The results of the present study give some indications of reduced fecundability for work with specific agents in laboratories, and support previously reported findings of a negative influence of organic solvents on fecundity among female laboratory personnel.

Adult↗
PubMed2001

Allium vegetables and organosulfur compounds: do they help prevent cancer?

Allium vegetables have been shown to have beneficial effects against several diseases, including cancer. Garlic, onions, leeks, and chives have been reported to protect against stomach and colorectal cancers, although evidence for a protective effect against cancer at other sites, including the breast, is still insufficient. The protective effect appears to be related to the presence of organosulfur compounds and mainly allyl derivatives, which inhibit carcinogenesis in the forestomach, esophagus, colon, mammary gland, and lung of experimental animals. The exact mechanisms of the cancer-preventive effects are not clear, although several hypotheses have been proposed. Organosulfur compounds modulate the activity of several metabolizing enzymes that activate (cytochrome P450s) or detoxify (glutathione S-transferases) carcinogens and inhibit the formation of DNA adducts in several target tissues. Antiproliferative activity has been described in several tumor cell lines, which is possibly mediated by induction of apoptosis and alterations of the cell cycle. Allium vegetables and organosulfur compounds are thus possible cancer-preventive agents. Clinical trials will be required to define the effective dose that has no toxicity in humans.

Allium↗
PubMed2001

Glutathione S-transferase M1, M3, P1, and T1 genetic polymorphisms and susceptibility to breast cancer.

This study was undertaken to examine if glutathione S-transferase (GST) M1, M3, P1, and T1 genotypes affected breast cancer risk in Finnish women. The study population consisted of 483 incident breast cancer cases and 482 healthy population controls. Genotyping analyses were performed by PCR-based methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected risk factors for breast cancer. When the genes were studied separately, the only significant finding was between GSTM1 null genotype and postmenopausal breast cancer risk (OR, 1.49; 95% CI, 1.03-2.15). Conversely, when the potential combined effects of the at-risk genotypes were examined, significant associations were observed only among premenopausal women. Although only a moderate risk of breast cancer was seen for premenopausal women concurrently carrying the GSTM3*B allele containing genotypes and the GSTP1 Ile/ Ile genotype (OR, 2.07; 95% CI, 1.02-4.18), the risk rose steeply if they simultaneously lacked the GSTT1 gene (OR, 9.93, 95% CI, 1.10-90.0). A borderline significant increase in the risk of breast cancer was also seen for premenopausal women with the combination of GSTM1 null, GSTP1 Ile/Ile, and GSTT1 null genotypes (OR, 3.96; 95% CI, 0.99-15.8). Our findings support the view that GST genotypes contribute to the individual breast cancer risk, especially in certain combinations.

Adult↗
PubMed2001

Polymorphic catechol-O-methyltransferase gene and breast cancer risk.

We examined 483 Finnish breast cancer cases and 482 population controls to determine the potential effect of catechol-O-methyltransferase (COMT) genotype in individual susceptibility to breast cancer. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression after adjustment for known or suspected risk factors for breast cancer. When studied separately by menopausal status, the COMT-L allele-containing genotypes were inversely associated with premenopausal breast cancer, especially with advanced stage of the disease (OR, 0.44; 95% CI, 0.22-0.87). Among postmenopausal women a similar decreased risk was seen for local carcinoma associated with the COMT-LL genotype (OR, 0.55; 95% CI, 0.31-0.98). The lowest breast cancer risk was seen in the postmenopausal women with the COMT-LL genotype and low body-mass index ( 30 months) use of estrogen (OR, 4.02; 95% CI, 1.13-14.3), or with the COMT-L allele-containing genotypes and early age (<or=12 years) at menarche (OR, 8.59; 95% CI, 1.85-39.8). Our study, therefore, suggests that the COMT genotype may define a portion of the individual breast cancer susceptibility that is associated with reproductive events and hormone exposure even if it does not seem to be a major overall risk factor for this malignancy.

Aged↗
PubMed2001

Alcoholism and risk for cancer of the cervix uteri, vagina, and vulva.

We conducted a population-based cohort study to analyze the risk of developing cancers of the female genitals among 36,856 patients with a hospital discharge diagnosis of alcoholism (ICD-7: 307, 322; ICD-8: 291, 303; ICD-9: 291, 303, 305A) in Sweden between 1965 and 1995. The follow-up was done by linkages of national registries. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were computed based on nationwide specific cancer rates. The first year of follow-up was excluded from all analyses to minimize the impact of selection bias. We found that alcoholic women had excess risks for in situ cervical cancer (SIR, 1.7; 95% CI, 1.6-1.9), for invasive cervical cancer (SIR, 2.9; 95% CI, 2.4-3.5), and for cancer of the vagina (SIR, 4.6; 95% CI, 2.2-8.5) but not for cancer of the vulva (SIR, 1.0; 95% CI, 0.4-2.0). The fact that alcoholics had an excess risk also for the in situ cancer suggests that the observed excess in invasive cervical cancer may not only be attributable to less use of Pap smear screening among them. The alcoholic women may be at higher risk for the progression from human papillomavirus infection to a malignant lesion for lifestyle-related reasons (promiscuity, smoking, use of contraceptive hormones, and dietary deficiencies). We conclude that alcoholic women are at high risk for in situ and invasive cervical cancer and for cancer of the vagina.

Adult↗
PubMed2000

An international evaluation of the cancer-preventive potential of sunscreens.

The IARC convened a working group of experts in Lyon, France, on 10-18 April, 2000, to evaluate the cancer-preventive activity of sunscreens and to compile the fifth volume of the IARC Handbooks of Cancer Prevention. The working group concluded that the topical use of sunscreens reduces the risk of sunburn in humans and that sunscreens probably prevent squamous-cell carcinoma of the skin when used mainly during unintentional sun exposure. No conclusion can be drawn about the cancer-preventive activity of topical use of sunscreens against basal-cell carcinoma and cutaneous melanoma. Use of sunscreens can extend the duration of intentional sun exposure, such as sunbathing. Such an extension may increase the risk for cutaneous melanoma. The working group warned against relying solely on sunscreens for protection from UV radiation.

Basal Cell Carcinoma↗
PubMed2000

Survival in operable non-small-cell lung cancer: role of p53 mutations, tobacco smoking and asbestos exposure.

Validated markers are needed to identify operable lung cancer patients with poor prognosis. About one-half of non-small-cell lung cancers (NSCLCs) carry a mutation in the p53 tumor-suppressor gene. We examined 101 NSCLC patients for surgical stage, completeness of resection, tobacco smoking, asbestos exposure, age, gender and p53 gene mutations as prognostic factors after a follow-up period of 4 years. Cox's multivariate regression model was applied to quantify the associations with overall and cancer-related survival. Patients with a wild-type p53 gene had an overall 4-year survival of 43% and those with a mutated p53 gene, 35%. In squamous-cell carcinoma, stage and heavy smoking, defined as the median of pack-years smoked, had prognostic significance for overall survival. Only stage was associated with poor cancer-related survival. Asbestos exposure was not associated with overall survival or cancer-related survival in squamous-cell carcinoma or adenocarcinoma. In adenocarcinoma, p53 mutation, in addition to stage, emerged as a significant predictor of poor cancer-related survival.

Adult↗
PubMed2000

Chemoprevention of cancer: lessons to be learned from beta-carotene trials.

Observational studies indicate a lower incidence of chronic diseases, including various cancers and cardiovascular disease, related to higher intakes of carotenoid containing foods (fruits and vegetables). Beta-carotene, one of the large number of naturally occurring carotenoids, thus appears to actively participate in health. However, recent intervention trials indicate that beta-carotene supplements are not efficacious in the prevention of cardiovascular disease and major cancers occurring in well-nourished populations. In fact, supplemental beta-carotene appears to increase, rather than to reduce, lung cancer incidence and deaths from cardiovascular disease in current smokers and in asbestos exposed workers. In order to resolve these paradoxes, we need to better understand the underlying biology, identify interactions, develop mechanistic hypotheses and test them in clinical trials in humans. Until that time, we should confine any premature enthusiasm for chemopreventive supplementation.

Antioxidants↗
PubMed2000

The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence.

OBJECTIVE: We have reviewed the potential cancer-preventive and other relevant properties of Panax ginseng C. A. Meyer, which has been traditionally used as a natural tonic in Oriental countries. DATA IDENTIFICATION AND STUDY SELECTION: Publications on Panax ginseng and its relation to cancer were obtained from the Medline database (1983-1998) and by checking reference lists to find earlier reports. The reports cover experimental models and human studies on cancer-preventive activity, carcinogenicity and other beneficial or adverse effects. In addition, possible mechanisms of chemoprevention by ginseng were considered. RESULTS: Published results from a cohort and two case-control studies in Korea suggest that the intake of ginseng may reduce the risk of several types of cancer. When ginseng was tested in animal models, a reduction in cancer incidence and multiplicity at various sites was noted. Panax ginseng and its chemical constituents have been tested for their inhibiting effect on putative carcinogenesis mechanisms (e.g., cell proliferation and apoptosis, immunosurveillance, angiogenesis); in most experiments inhibitory effects were found. CONCLUSION: While Panax ginseng C. A. Meyer has shown cancer-preventive effects both in experimental models and in epidemiological studies, the evidence is currently not conclusive as to its cancer-preventive activity in humans. The available evidence warrants further research into the possible role of ginseng in the prevention of human cancer and carcinogenesis.

Animals↗
PubMed2000

CYP2D6 ultrarapid metabolizer genotype as a potential modifier of smoking behaviour.

Some 3-10% of Caucasians are deficient in CYP2D6 metabolism (poor metabolizers), due to inheritance of two defective alleles, whereas amplification of the CYP2D6 gene results in ultrarapid metabolism in 1-2% of Caucasian populations. To examine the possible association between CYP2D6 polymorphism and individual smoking behaviour, we analysed the prevalence of CYP2D6 genotypes among 292 long-term heavy smokers, 382 individuals with more variable smoking histories, and 302 never-smokers. The prevalence of ultrarapid metabolizers in heavy smokers (7.9%) was twofold compared to individuals with variable smoking habits (3.7%; odds ratio 2.3, 95% confidence interval 1.2-4.4), and fourfold compared with never-smokers (2.0%) (odds ratio 4.2, 95% confidence interval 1.8-9.8). The frequency of poor metabolizer genotype was approximately 2%, in each smoker group. However, when men and women were studied separately, the prevalence of poor metabolizer genotype was higher in male never-smokers (3.6%) than in variable smokers (2.7%) and heavy smokers (2.2%). Moreover, a trend test, adjusted by age, gender and cancer status, revealed a significant trend for the increased tobacco usage with increased metabolic capacity. Our results are in agreement with the assumption that increased CYP2D6 activity may contribute to the probability of being addicted to smoking.

Age Distribution↗
PubMed2000

An uncommon phenotype of poor inducibility of CYP1A1 in human lung is not ascribable to polymorphisms in the AHR, ARNT, or CYP1A1 genes.

Cigarette smoking can induce CYP1A1 in the lung. Induction requires the aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor nuclear translocator (ARNT) proteins. Lung samples from seven of 75 Finnish patients who smoked until the time of surgery exhibited absent or low levels of CYP1A1 protein, mRNA and enzymatic activity, suggesting that these individuals might be genetically non or poorly inducible for CYP1A1. All seven lung samples expressed normal levels of AHR mRNA and ARNT mRNA, indicating that they did not carry inactivating polymorphisms in the 5' upstream regulatory regions of these genes. Sequencing of cDNAs encompassing the complete coding regions of AHR and ARNT identified a previously known codon 554 polymorphism in AHR, which was present in the homozygous state in one individual. This polymorphism, which leads to an amino acid substitution, has previously been reported either to have no effect or to enhance CYP1A1 induction. Previously unreported silent single nucleotide polymorphisms were identified in codon 44 of AHR and codon 189 of ARNT. 1500 bp of genomic sequence from the 5' upstream regulatory sequence of the CYP1A1 gene was also sequenced in the non-inducible individuals. A nucleotide substitution polymorphism at position -459 was detected in the heterozygous state in two individuals. This polymorphic site does not reside in any known regulatory sequence. The complete CYP1A1 coding sequence and intron/exon boundaries were then sequenced. None of the non or poorly inducible individuals exhibited any polymorphisms, either homozygous or heterozygous compared to representative inducible individuals or the previously published CYP1A1 sequence. Thus, no polymorphisms in the AHR, ARNT or CYP1A1 genes were identified that could be responsible for the non/low inducibility phenotype observed.

Aryl Hydrocarbon Receptor Nuclear Translocator↗