7-Alkylguanine adducts of styrene oxide determined by 32P-postlabelling in DNA and human embryonal lung fibroblasts (HEL)

The modified ³²P-postlabelling method was used for the detectionof N-7-(2-hydroxy-phenylethyl) guanine adducts in DNA and humanembryonal lung (HEL) cells treated in vitro with styrene oxide(SO). The total recovery of 7-alkylguanine adducts of styreneoxide in DNA analysed by ³²P-postlabelling assay was 4.1±0.6%.The disappearance of 7-alkyldeoxyguanosine monophosphate adductsfrom SO-modified DNA at 37°C showed a half-life of 19 h.The levels of 7-alkylguanine DNA adducts and single-strand breaks(SSBs) in DNA were determined in HEL cells treated with SO for3 and 18 h. In the 3 h treatment there was a concentration-dependentincrease of both 7-alkylguanine adducts and SSBs in DNA (r =0.98, P = 0.012 and r = 0.99, P = 0.003, respectively). We founda significant correlation between 7-alkylguanine DNA adductsand SSBs in DNA (r = 0.98, P = 0.011). In HEL cells     

Oral contraceptive use before first birth and risk of breast cancer: a case control study

Background  

Our investigation sought to compare changes in sexual function following supracervical hysterectomy (SCH) and total abdominal hysterectomy (TAH).     

Time trends and familial risks in squamous cell carcinoma of the skin

OBJECTIVES: To study time trends and familial clustering of invasive and in situ squamous cell skin cancers (SCC), with particular reference to sun-exposed and covered sites of the body. DESIGN: Epidemiologic follow-up study of the whole population. SETTING: The Swedish Family-Cancer Database from the year 2000, to cover individuals born after 1931 with their biological parents, totaling 10.2 million persons. PATIENTS: Cancer data were obtained from the Swedish Cancer Registry from 1961 through 1998 and included 1907 invasive SCCs in offspring and 12,702 and 7167 in fathers and mothers, respectively. The numbers of patients affected by in situ SCC were 2666, 13,739, and 13,321, respectively. MAIN OUTCOME MEASURES: Standardized incidence ratios and 95% confidence intervals were calculated for SCC in offspring when parents had SCC. Incidence rates were calculated for the population in the Database. RESULTS: Incidence trends showed a large increase in reported cases of SCC and particularly of in situ SCC. Among invasive cases, the increase was largest among covered sites. A clear cohort effect was observed particularly for SCC on covered sites. Familial standardized incidence ratios for offspring combining invasive and in situ SCC were 2.25 (95% confidence interval, 1.93-2.59) for concordant exposed sites and 2.60 (95% confidence interval, 1.38-4.20) for concordant covered sites, suggesting no difference between the body parts within the present statistical power. CONCLUSIONS: The higher increase in incidence on covered sites and the strong cohort effect suggest a contribution by intentional tanning. The observed equal increase in the familial effect on exposed and covered sites suggests that familial risk increases proportionately to the background rate.     

Effect of the spectral range of a UV lamp on the production of cyclobutane pyrimidine dimers in human skin in situ

BACKGROUND: Ultraviolet (UV) irradiation has a broad spectrum of biological effects and a capacity to initiate skin carcinogenesis through DNA damage. The effect of different wave bands of UV light on the production of DNA damage in human skin in situ was studied with a broadband UV-B lamp TL-12 and a narrowband UV-B lamp TL-01. METHODS: Eight psoriasis patients participated in the study. Their minimal erythema dose was assessed separately for the two UV-B wave band ranges. Test areas of buttock skin were irradiated with the two spectrally differing lamps using erythemally equivalent UV doses of 40 and 80 mJ/cm2 CIE (Commission International de I'Eclairage). Punch biopsies were taken from the irradiated areas, and UV-induced DNA lesions (cyclobutane pyrimidine dimers, CPDs) in the skin were analyzed with a 32P high-performance liquid chromatography postlabelling method. RESULTS: No UV source-dependent differences in the induced levels of CPDs were detected in this study. CONCLUSION: CPD production with broadband TL-12 and narrowband TL-01 UV-B lamps in situ did not differ when erythemally equivalent UV doses were used. The preliminary result needs to be confirmed in a larger study.     

Familial and second esophageal cancers: a nation-wide epidemiologic study from Sweden

A few case-control studies have been published on familial risks in esophageal cancer. Reliable data on familial risks are needed for prevention and clinical decisions. We used the nation-wide Swedish Family-Cancer Database on 10.1 million individuals and close to 6000 esophageal cancers to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for esophageal cancer in 0-66-year-old offspring by cancers in family members. Additionally, SIRs for second esophageal cancers were analyzed. The SIR for esophageal cancer was 3.91 (95% CI 1.55-7.35) when a parent presented with esophageal cancer and 4.91 (95% CI 1.77-9.62) when a parent presented with squamous cell carcinoma. The sibling risk for esophageal cancer was increased but was based on 1 pair only. The population-attributable proportion of familial esophageal cancer was 0.70%. Risks for second esophageal cancers were increased after upper aerodigestive tract, esophageal, stomach, larynx, and lung cancers. The data on second cancers suggest that environmental factors are important for esophageal cancer and probably contribute to the familial clustering. However, the high familial risk of 3.91 is unlikely without the involvement of heritable factors. The population-attributable proportion of familial esophageal cancer is small.     

A case-control study of childhood leukaemia and paternal occupational contact level in rural Sweden

In a national case-control study in Sweden, we investigated whether in rural areas (where susceptible individuals are more prevalent than in urban areas) leukaemia risk was higher among the young children of fathers with many work contacts, as the infective hypothesis has predicted. A total of 1935 cases diagnosed in 1958-1998 together with 7736 age-matched (within 1 year) population controls (of whom 970 and 3880 respectively were aged 0-4) were linked to paternal occupational details as recorded in the census closest to the year of birth. Applying the two classifications of occupational contact level used in a study of rural Scotland, the odds ratios for children aged 0-4 years in the highest contact category (which includes teachers) in the most rural Swedish counties were 3.47 (95% CI 1.54, 7.85) and 1.59 (1.07, 2.38) respectively, relative to the medium and low (reference) category; no such excess was found in urban or intermediate counties. There was also a significant positive trend at ages 0-4 in the rural counties across the three levels of increasing occupational contact (P for trend 0.02 and 0.03, respectively), but again not in the urban or intermediate counties. No such effect or trend was found at ages 5-14 in any of the three county groupings. The findings confirm those of a recent study in rural Scotland, and also suggest that unusual population mixing (as occurred in Scotland as a result of the North Sea oil industry) is not a necessary requirement for the effect, since comparable mixing has not been a feature of rural Sweden.     

The XPD variant alleles are associated with increased aromatic DNA adduct level and lung cancer risk

The DNA repair protein xeroderma pigmentosum complementation group D (XPD) is involved in the nucleotide excision repair of DNA lesions induced by many tobacco and environmental carcinogens. In order to study the functional impact of the common polymorphisms in XPD exon 10 (G > A, Asp312Asn) and exon 23 (A > C, Lys751Gln), we have genotyped 185 Swedish lung cancer cases (97 smokers and 88 never-smokers) and 162 matched population controls (83 smokers and 79 never-smokers). Presence of one or two variant alleles was associated with increased risk for lung cancer among never-smokers only, in particular younger (<70 years) never-smokers [odds ratio (OR) = 2.6, 95% confidence interval (CI) = 1.1-6.5 for exon 10; OR = 3.2, 95% CI = 1.3-8.0 for exon 23, adjusted for age, gender and environmental tobacco smoke]. Aromatic DNA adduct level (AL) in peripheral lymphocytes was found to be similar between cases and controls, but significantly increased by current or recent smoking. Overall, there was a significant trend for increasing AL with increasing number of variant alleles in exon 10 (P = 0.02) or in exon 23 (P = 0.001). In addition, subjects with the combined exon 10 AA and exon 23 CC genotype showed a significantly higher AL compared with all those with any of the other genotypes (P = 0.02). We conclude that the XPD variant alleles may be associated with reduced repair of aromatic DNA adducts in general and increased lung cancer risk among never-smokers.     

Lifestyle and cancer: effect of parental divorce.

According to previous studies, divorced individuals have increased risks of cancers related to alcohol and tobacco consumption and sexual habits, but the increases are balanced with decreased risks of many common cancers. In the present study, cancer risks were analyzed for 0-70-year-old offspring of divorced parents, on the basis the Swedish Family-Cancer Database with cancer data from the years 1958 to 2002. We calculated standardized incidence ratios for cancer among offspring of divorced parents (19,000 cancer patients) and compared them with offspring of stably married parents (121,000 cancer patients). Standardized incidence ratios were adjusted for many factors, including socio-economic status. Offspring of divorced parents were divided into groups depending on whether their mothers, fathers or both had had children with different partners. Offspring of divorced parents had an increased risk of upper aerodigestive tract, esophageal, anal, pancreatic, lung and cervical cancers. Decreased risks were noted for Hodgkin's disease and bone cancer. For Hodgkin's disease, the data suggest protective effects through early exposure to childhood pathogens but for bone cancer mechanisms remain to be established. The overall cancer risk for offspring of divorced parents was at or above unity. The results show that offspring of divorced parents have increased cancer risks at tobacco-related, alcohol-related and sex-related sites, in analogy to their parent, but they lack decreased risks at common sites, experienced by their parents. Divorce is becoming increasingly common in many countries and any deviant cancer patterns among offspring of divorced parents will have an impact on the population risk.