Maternal smoking during pregnancy and fetal biometry: the INMA Mother and Child Cohort Study.

In utero tobacco exposure has been associated with fetal growth restriction, but uncertainty remains about critical windows of exposure and specific effects on body segments. In the present study, we aimed to examine the association of maternal smoking with fetal biometry in different stages of pregnancy. The study population comprised 2,478 fetuses from a Spanish birth cohort study that was established between 2003 and 2008. Biparietal diameter, femur length, abdominal circumference, and estimated fetal weight were evaluated at 12, 20, and 34 weeks of gestation. Fetal size and growth were assessed by standard deviation scores adjusted by maternal and fetal characteristics. Maternal smoking was assessed using questionnaire and a sample of urinary cotinine at week 32 of gestation. Associations were estimated using multiple regression analysis. Smokers at week 12 of gestation showed decreased fetal growth as reflected by all growth parameters at 20-34 weeks, leading to a reduced fetal size at week 34. The reduction was greatest in femur length, at -9.4% (95% confidence interval -13.4, -5.4) and least in abdominal circumference, at -4.4% (95% CI: -8.7, -0.1). Fetuses of smokers who quit smoking before week 12 showed reduced growth only in femur length (-5.5; 95% CI: -10.1, -0.9). Dose-response curves for smoking versus fetal growth parameters (abscissa: log2 cotinine) were linear for biparietal diameter and femur length.

Genetic polymorphisms in CYP1A1, GSTM1, GSTP1 and GSTT1 metabolic genes and risk of lung cancer in Asturias.

BACKGROUND: Metabolic genes have been associated with the function of metabolizing and detoxifying environmental carcinogens. Polymorphisms present in these genes could lead to changes in their metabolizing and detoxifying ability and thus may contribute to individual susceptibility to different types of cancer. We investigated if the individual and/or combined modifying effects of the CYP1A1 MspI T6235C, GSTM1 present/null, GSTT1 present/null and GSTP1 Ile105Val polymorphisms are related to the risk of developing lung cancer in relation to tobacco consumption and occupation in Asturias, Northern Spain. METHODS: A hospital-based case-control study (CAPUA Study) was designed including 789 lung cancer patients and 789 control subjects matched in ethnicity, age, sex, and hospital. Genotypes were determined by PCR or PCR-RFLP. Individual and combination effects were analysed using an unconditional logistic regression adjusting for age, pack-years, family history of any cancer and occupation. RESULTS: No statistically significant main effects were observed for the carcinogen metabolism genes in relation to lung cancer risk. In addition, the analysis did not reveal any significant gene-gene, gene-tobacco smoking or gene-occupational exposure interactions relative to lung cancer susceptibility. Lastly, no significant gene-gene combination effects were observed. CONCLUSIONS: These results suggest that genetic polymorphisms in the CYP1A1, GSTM1, GSTT1 and GSTP1 metabolic genes were not significantly associated with lung cancer risk in the current study. The results of the analysis of gene-gene interactions of CYP1A1 MspI T6235C, GSTM1 present/null, GSTT1 present/null and GSTP1 Ile105Val polymorphisms in lung cancer risk indicate that these genes do not interact in lung cancer development.

Alcohol Consumption and Lung Cancer According to Ile349Val Polymorphism in ADH3 Gene: Beyond the Tobacco Smoking Effect.

Objectives: Smoking is the leading cause of lung cancer. However, several studies have suggested other factors such as alcohol consumption could also play a role through polymorphisms associated with alcohol metabolism. We investigated the association between alcohol consumption and lung cancer according to the Ile349Val polymorphism in the alcohol dehydrogenase 3 ADH3 gene. Methods: We carried out a hospital-based case-control study, a total of 402 incident cases of lung cancer and 383 controls were genotyped for the Ile349Val polymorphism by polymerase chain reaction combined with restriction fragment length polymorphism. Alcohol consumption and other variables were measured using questionnaires in personal interviews. We used multiple logistic regressions to estimate adjusted odd ratios using and 95% confidence intervals. Results: In multivariate analysis, an increased risk of lung cancer was observed for the highest category of alcohol consumption (≥30 g/day), although it does not reach statistical significance (OR=1.60, 95% CI: 0.91-2.83). Besides, an increased risk of lung cancer was observed in the highest category of alcohol consumption for the Ile/Val genotype compared with the Ile/Ile genotype (OR=2.35, 95% CI: 1.04-5.33). Conclusions: This study suggests that beyond smoking consumption, a high consumption of alcohol might increase the risk of lung cancer. No clear association was found between alcohol consumption and lung cancer according to the Ile349Val polymorphism in ADH3 gene.

Effect of alcohol and its metabolites in lung cancer: CAPUA study. / Efecto del alcohol y sus metabolitos en el cáncer de pulmón: estudio CAPUA.

BACKGROUND AND OBJECTIVE: Alcohol and its metabolites play an important role in carcinogenesis. This effect could be modulated by polymorphisms in genes encoding enzymes involved in the metabolism of alcohol and folate. Therefore, we analyzed the effect of alcohol consumption and ADH1B Arg48His, ADH1B Arg370Cys, ADH1C Ile349Val, ALDH2 Glu540Lys, CYP2E1 RsaI, CYP2E1 DraI, CYP2E1 TaqI and MTHFR C677T polymorphisms on the risk of developing lung cancer. PATIENTS AND METHODS: We included 876 lung cancer cases and 840 controls of the CAPUA hospital-based case-control study. Genotyping was performed using the Sequenom MassArray (iPLEX GOLD) technology. RESULTS: An alcohol consumption of 0.1-9.9g/day decreased lung cancer risk (ORadjusted=0.71; 95% CI 0.48-1.05), although statistical significance was not achieved. A consumption≥30g/day of alcohol and≥36PY of tobacco increases lung cancer risk (ORadjusted=26.68; 95% CI 12.69-56.10). On the other hand, a high consumption of vegetables (≥116.65g/day) and fruits (≥233.13g/day) decreases lung cancer risk with an alcohol consumption of 0.1-9.9g/day (ORadjusted=0.52; 95% CI 0.30-0.89; ORadjusted=0.58; 95% CI 0.33-1.03, respectively). An alcohol consumption of 10-29.9g/day in ADH1B 48His allele-carriers increases lung cancer risk (ORadjusted=3.32; 95% CI 1.03-10.70). CONCLUSIONS: Alcohol and polymorphisms in genes involved in the metabolism of alcohol and folate are related to the onset of lung cancer.

Association of p21 Ser31Arg and p53 Arg72Pro polymorphisms with lung cancer risk in CAPUA study.

BACKGROUND: The aim of this study was to investigate how Ser31Arg polymorphisms in p21 may modify lung cancer susceptibility. Because p21 is the major downstream mediator of p53, we analyzed the combined effect of two polymorphisms, p21 Ser31Arg and TP53 Arg72Pro, to elucidate whether polymorphic variants determine the risk of lung cancer. METHODS: This was designed as a hospital-based case-control study, and included 675 cases and 675 control subjects matched by ethnicity, gender, and age. Genotypes were determined by polymerase chain reaction restriction fragment length polymorphism, and multivariate unconditional logistic regression was performed to analyze the results. RESULTS: Subjects who carried the p21 Ser31Arg allele had a higher risk of lung cancer (adjusted odds ratio [OR] 1.38; 95% confidence interval [CI] 0.99-2.03). This risk was increased in men aged younger than 55 years (adjusted OR 2.35; 95% CI 1.00-5.51). Smokers had an increased risk of lung cancer (adjusted OR 2.23; 95% CI 1.24-4.02). Men younger than 55 years carrying risk alleles for both genes (p21 Ser31Arg and TP53 Arg72Pro) had an increased risk (adjusted OR 5.78; 95% CI 1.38-24.19), as did smokers with both risk alleles (adjusted OR 4.52; 95% CI 1.52-13.50). CONCLUSION: The presence of both variant alleles increased the risk of developing lung cancer in men, particularly in smokers younger than 55 years.

Efecto del alcohol y sus metabolitos en el cáncer de pulmón: estudio CAPUA / Effect of alcohol and its metabolites in lung cancer: CAPUA study

Antecedentes y objetivo: El alcohol y sus metabolitos tienen un papel importante en la carcinogénesis, pudiendo estar este efecto modulado por polimorfismos en genes que codifican enzimas participantes en el metabolismo de alcohol y folato. Por ello, analizamos el efecto que podría tener el consumo de alcohol y los polimorfismos ADH1B Arg48His, ADH1B Arg370Cys, ADH1C Ile349Val, ALDH2 Glu540Lys, CYP2E1 RsaI, CYP2E1 DraI, CYP2E1 TaqI y MTHFR C677T en el riesgo de cáncer de pulmón. Pacientes y método: Se incluyeron 876 casos de cáncer de pulmón y 840 controles del estudio caso-control de base hospitalaria CAPUA. El genotipado de los SNP se realizó mediante la tecnología Sequenom MassArray (iPLEX GOLD). Resultados: Un consumo de alcohol de 0,1-9,9g/día disminuye el riesgo de cáncer de pulmón (ORajustada = 0,71; IC 95% 0,48-1,05), aunque no se alcanza la significación estadística. Un consumo de alcohol ≥ 30g/día y de tabaco ≥ 36 paquetes/año aumenta el riesgo de cáncer de pulmón (ORajustada = 26,68; IC 95% 12,69-56,10). Por otro lado, un consumo elevado de verduras (≥ 116,65g/día) o de frutas (≥ 233,13g/día) disminuye el riesgo de cáncer de pulmón con un consumo de alcohol de 0,1-9,9 g/día (ORajustada = 0,52; IC 95% 0,30-0,89; ORajustada = 0,58; IC 95% 0,33-1,03, respectivamente). Un consumo de alcohol de 10-29,9 g/día en individuos portadores del alelo ADH1B 48His aumenta el riesgo de cáncer de pulmón (ORajustada = 3,32; IC 95% 1,03-10,70). Conclusiones: El alcohol y polimorfismos en genes que participan en el metabolismo del alcohol y del folato están relacionados con el cáncer de pulmón (AU)

Background and objective: Alcohol and its metabolites play an important role in carcinogenesis. This effect could be modulated by polymorphisms in genes encoding enzymes involved in the metabolism of alcohol and folate. Therefore, we analyzed the effect of alcohol consumption and ADH1B Arg48His, ADH1B Arg370Cys, ADH1C Ile349Val, ALDH2 Glu540Lys, CYP2E1 RsaI, CYP2E1 DraI, CYP2E1 TaqI and MTHFR C677T polymorphisms on the risk of developing lung cancer. Patients and methods: We included 876 lung cancer cases and 840 controls of the CAPUA hospital-based case-control study. Genotyping was performed using the Sequenom MassArray (iPLEX GOLD) technology. Results: An alcohol consumption of 0.1-9.9g/day decreased lung cancer risk (ORadjusted = 0.71; 95% CI 0.48-1.05), although statistical significance was not achieved. A consumption ≥ 30g/day of alcohol and ≥ 36PY of tobacco increases lung cancer risk (ORadjusted = 26.68; 95% CI 12.69-56.10). On the other hand, a high consumption of vegetables (≥ 116.65g/day) and fruits (≥ 233.13g/day) decreases lung cancer risk with an alcohol consumption of 0.1-9.9g/day (ORadjusted = 0.52; 95% CI 0.30-0.89; ORadjusted = 0.58; 95% CI 0.33-1.03, respectively). An alcohol consumption of 10-29.9 g/day in ADH1B 48His allele-carriers increases lung cancer risk (ORadjusted = 3.32; 95% CI 1.03-10.70). Conclusions: Alcohol and polymorphisms in genes involved in the metabolism of alcohol and folate are related to the onset of lung cancer (AU)