Biomedical subjects

Kim Overvad

Publications and source records attributed to Kim Overvad.

At least 73 records · Page 4Linked to original sources

PubMed2005

Effect of polymorphisms in XPD, RAI, ASE-1 and ERCC1 on the risk of basal cell carcinoma among Caucasians after age 50.

We have investigated the occurrence of basal cell carcinoma (BCC) in relation to a number of single nucleotide polymorphisms (SNPs) in the chromosomal region 19q13.2-3. A case-control study including 322 basal cell carcinoma cases and a similar number of controls was nested in a population-based prospective investigation encompassing 57,053 Danes (aged 50-64 at inclusion) living in Copenhagen or Aarhus in Denmark. We found that the polymorphism XPD Arg156Arg was associated with risk of basal cell carcinoma (rate ratio (RR)=1.59, 95% confidence interval (CI)=1.02-2.50 for homozygous carriers of the A-allele), and that the association was strongest in the youngest age interval of the study group (50-55 years) (RR=2.33, 95% CI=1.03-5.28). The polymorphisms XPD Asp312Asn and XPD Lys751Gln were not associated with risk of basal cell carcinoma. While it cannot be ruled out that the present findings are due to chance, the present results are consistent with previous findings that XPD Arg156Arg is a weak risk factor for basal cell carcinoma.

Age of Onset↗

PubMed2005

Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study.

OBJECTIVE: To examine whether adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, is associated with longer life expectancy among elderly Europeans. DESIGN: Multicentre, prospective cohort study. SETTING: Nine European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, United Kingdom). PARTICIPANTS: 74,607 men and women, aged 60 or more, without coronary heart disease, stroke, or cancer at enrolment and with complete information about dietary intake and potentially confounding variables. MAIN OUTCOME MEASURES: Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale, and death from any cause by time of occurrence, modelled through Cox regression. RESULTS: An increase in the modified Mediterranean diet score was associated with lower overall mortality, a two unit increment corresponding to a statistically significant reduction of 8% (95% confidence interval 3% to 12%). No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain. When dietary exposures were calibrated across countries, the reduction in mortality was 7% (1% to 12%). CONCLUSION: The Mediterranean diet, modified so as to apply across Europe, was associated with increased survival among older people.

Aged↗

PubMed2005

Consumption of vegetables and fruits and risk of breast cancer.

CONTEXT: The intake of vegetables and fruits has been thought to protect against breast cancer. Most of the evidence comes from case-control studies, but a recent pooled analysis of the relatively few published cohort studies suggests no significantly reduced breast cancer risk is associated with vegetable and fruit consumption. OBJECTIVE: To examine the relation between total and specific vegetable and fruit intake and the incidence of breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 285,526 women between the ages of 25 and 70 years, participating in the European Prospective Investigation Into Cancer and Nutrition (EPIC) study, recruited from 8 of the 10 participating European countries. Participants completed a dietary questionnaire in 1992-1998 and were followed up for incidence of cancer until 2002. MAIN OUTCOME MEASURES: Relative risks for breast cancer by total and specific vegetable and fruit intake. Analyses were stratified by age at recruitment and study center. Relative risks were adjusted for established breast cancer risk factors. RESULTS: During 1,486,402 person-years (median duration of follow-up, 5.4 years), 3659 invasive incident breast cancer cases were reported. No significant associations between vegetable or fruit intake and breast cancer risk were observed. Relative risks for the highest vs the lowest quintile were 0.98 (95% confidence interval [CI], 0.84-1.14) for total vegetables, 1.09 (95% CI , 0.94-1.25) for total fruit, and 1.05 (95% CI , 0.92-1.20) for fruit and vegetable juices. For 6 specific vegetable subgroups no associations with breast cancer risk were observed either. CONCLUSION: Although the period of follow-up is limited for now, the results suggest that total or specific vegetable and fruit intake is not associated with risk for breast cancer.

Adult↗

PubMed2005

C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVES: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated. RESULTS: BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women. CONCLUSIONS: Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.

Androgens↗

PubMed2005

Generalized additive models applied to analysis of the relation between amount and type of alcohol and all-cause mortality.

The J-shaped relation between alcohol intake and mortality is well established, whereas the nadir of the curve is not determined. Due to non-linearity of the relation, categorical alcohol variables have been used to model the relation. In Generalized Additive Models (GAM) non-linear relations can be modelled without the disadvantages of categorization and without assumptions regarding the functional form. The aim of this study was to use GAM to evaluate the relation between alcohol intake, amount and type, and mortality. The relation was investigated using data from the Copenhagen City Heart Study (11,920 participants of whom 5552 died during 20 years follow-up). Using GAM, a smooth J-shaped relation between alcohol and mortality was found. However, if non-drinkers were categorized separately there was a positive association between alcohol and mortality even for low alcohol intake. For equal total alcohol intake, men and women drinking wine or spirits had lower mortality than beer drinkers. The nadir of the relation between alcohol and mortality was sensitive to the handling of non-drinkers. When non-drinkers were categorized separately we found no indication of a beneficial influence of low alcohol intake on mortality.

Adolescent↗

PubMed2005

Chlamydia pneumoniae seropositivity and risk of ischemic stroke: a nested case-control study.

Chlamydia pneumoniae has been linked with increased risk of cardiovascular disease, but data on stroke are sparse. We examined whether seropositivity to Chlamydia pneumoniae was associated with the risk of ischemic stroke in a nested case-control study. Data on Chlamydia pneumoniae serology, lifestyle factors, and medical history were obtained at baseline. Verified cases (n = 254) were compared with gender- and age-matched controls (n = 254). Positive IgA (> or = 1:16) or IgG (> or = 1:64) titers were associated with an increased risk of acute ischemic stroke, i.e. adjusted odds ratios (ORs) were 1.54 (95% confidence interval, CI: 0.96-2.47) and 1.28 (95% CI: 0.83-1.95). The adjusted OR was 1.77 (95% CI: 1.04-3.00) when both titers were elevated. The highest point estimates were seen for ischemic stroke due to large-artery atherosclerosis, adjusted OR: 6.32 (95% CI: 0.76-52.61) (IgG (> or = 1:64)). No clear associations were found for other types of ischemic stroke. The strength of the association varied depending on gender and the chosen cut-off values for the antibody titers. These results partly support the hypothesis that serologic evidence of Chlamydia pneumoniae infection may be associated with an increased risk of ischemic stroke. However, the risk may differ according to gender, subtype of ischemic stroke, and cut-off value of antibody titers.

Aged↗

PubMed2005

Dietary patterns among older Europeans: the EPIC-Elderly study.

Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a 'vegetable-based' diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a 'sweet- and fat-dominated' diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. 'Vegetable-based' and a 'sweet- and fat-dominated' diets are prevalent among the elderly across Europe, and there is a north-south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival.

Age Distribution↗

PubMed2005

Dietary carbohydrate intake is not associated with the breast cancer incidence rate ratio in postmenopausal Danish women.

Although many case-control studies have suggested positive associations between carbohydrate intake and breast cancer incidence rates in both pre- and postmenopausal women, there is limited information available from cohort studies. We examined the effect of the intake of different carbohydrates, the glycemic index, and the glycemic load on breast cancer incidence in postmenopausal women taking into consideration tumor estrogen receptor status. Postmenopausal women (n = 23,870; aged 50-65 y) participated in the "Diet, Cancer, and Health" study, and provided information about diet and established risk factors for breast cancer. During follow-up, we identified 634 incidents of breast cancer. Associations between carbohydrate intake and breast cancer incidence were analyzed using Cox's regression models. There was no association for intake of glucose, fructose, sucrose, maltose, lactose, or starch and breast cancer incidence rate, and no association for glycemic index or glycemic load after adjusting for confounding factors. Intake of different carbohydrates was not associated with breast cancer incidence rates for either estrogen receptor positive (ER+) or (ER-) breast cancer. Similarly, glycemic index and glycemic load were not associated with ER+ breast cancer after adjusting for confounding factors. A borderline significant positive association between glycemic index and (ER-) breast cancer was observed (P = 0.05). In conclusion, we found no clear associations between intake of different carbohydrates, total carbohydrate intake, glycemic index, or glycemic load and breast cancer incidence in postmenopausal women. Furthermore, when ER+ and ER- breast cancer cases were analyzed separately, no clear associations were observed.

Breast Neoplasms↗

PubMed2005

Self-reported and technician-measured waist circumferences differ in middle-aged men and women.

We investigated the agreement between 1) self-reported and technician-measured waist circumference at the level of the umbilicus, 2) circumference measured at the level of the umbilicus and halfway between the lower rib and the iliac crest (the natural waist), and 3) self-reported circumference at the level of the umbilicus and technician-measured circumference at the natural waist. At follow-up in the Danish "Diet, Cancer and Health" study, we recruited 176 men and 240 women for a validation study. Bland-Altman plots were used to evaluate agreement among measurement sites. Multiple regression was used to identify variables explaining the difference between measurements. The participants underestimated their waist circumference; the mean differences were -1.6 cm (95% CI: -2.4 cm, -0.8 cm) in men and -3.0 cm (95% CI: -3.8 cm, -2.3 cm) in women. Limits of agreement were from -11.9 to +8.7 cm among men and -14.9 to +8.9 cm among women. High BMI and large baseline waist circumference were associated with a larger degree of underreporting. Waist circumference measured at the level of the umbilicus was larger than at the natural waist; the mean differences were +0.7 cm (95% CI: +0.4 cm, +1.1 cm) in men and +5.0 cm (95% CI: +4.4 cm, +5.6 cm) in women. The self-reported waist circumference at the level of the umbilicus was correlated with the technician-measured circumference at the natural waist. The circumference at the natural waist was overestimated for women, depending on baseline waist circumference, and slightly underestimated for men, depending on baseline BMI.

Abdomen↗

PubMed2005

Is the association with fiber from foods in colorectal cancer confounded by folate intake?

The effect of multivariate adjustment including folate on the strong protective effect of fiber in foods on colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition was investigated in 1,721 cases identified in the latest follow-up. The inclusion of an additional 656 cases confirmed our previously published results, with a strong and significant reduction in colorectal cancer risk of approximately 9% for each uncalibrated quintile increase in fiber (P(linear trend) < 0.001) compared with an 8% reduction in our previous report, which had not been adjusted for folate. Inclusion of the other covariates (physical activity, alcohol, smoking, and red and processed meat) confirmed this significant inverse association for colon cancer and strengthened the association with left-sided colon cancer (P < 0.001). After maximum adjustment, the association between fiber and rectal cancer was not significant, as in our previous analysis. The association with fiber from different food sources was analyzed, but again, there were no significance trends after maximum adjustment.

Cohort Studies↗

PubMed2005

Urinary hydroxyestrogens and breast cancer risk among postmenopausal women: a prospective study.

BACKGROUND: It has been suggested that a low level of the 2-hydroxyestrogen metabolites (2-OHE) and a high level of 16alpha-hydroxyestrone (16alpha-OHE1) are associated with an enhanced risk of breast cancer. We examined the association between the metabolite levels and breast cancer in a nested case-control study, which also addressed hormone replacement therapy (HRT) and estrogen receptor status of the tumors. METHODS: 24,697 postmenopausal Danish women were enrolled in the "Diet, Cancer and Health" cohort. During follow-up, 426 breast cancer cases were identified and controls were matched by age at diagnosis, baseline age, and HRT use. The concentrations of 2-OHE and 16alpha-OHE1 in spot urine were measured by an enzyme immunoassay. Incidence rate ratios (IRR) and 95% confidence intervals (95% CI) were estimated for total and estrogen receptor-specific breast cancer and were stratified according to HRT use. RESULTS: A higher incidence of estrogen receptor-positive breast cancer with an enhanced 2-OHE level was observed among current HRT users, IRR per doubling = 1.30 (95% CI, 1.02-1.66), whereas no association was seen among nonusers of HRT, IRR per doubling = 1.00 (95% CI, 0.69-1.45). The association between estrogen receptor-positive breast cancer and the 16alpha-OHE1 metabolite level was in the opposite direction but slightly weaker and statistically insignificant. For estrogen receptor-negative breast cancer, no significant associations were seen. CONCLUSIONS: The risk of breast cancer, in particular the estrogen receptor-positive type, was enhanced among postmenopausal women using estradiol-based HRT and among those who had a high 2-OHE concentration.

Biomarkers↗

PubMed2005

4-Aminobiphenyl-hemoglobin adducts and risk of smoking-related disease in never smokers and former smokers in the European Prospective Investigation into Cancer and Nutrition prospective study.

The aim of this study was to evaluate whether biomarkers of environmental tobacco smoke exposure [i.e., 4-aminobiphenyl-hemoglobin (4-ABP-Hb) adducts] were predictive of the risk of tobacco-related cancers and diseases. We did a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, involving 190 controls and 149 cases (incident cancer of the lung, bladder, pharynx, larynx, oral cavity, leukemias, and chronic obstructive pulmonary disease or emphysema deaths). All individuals were never smokers or ex smokers for >10 years. 4-ABP-Hb adducts were analyzed in peripheral blood collected before the onset of the disease (median, 7 years). Overall, 4-ABP-Hb adducts were higher, although not statistically significantly so, in cases (as a whole) than controls. In the control population, high fruit and vegetable consumption significantly lowered the frequency of detectable adducts (Fisher's exact test, P = 0.025). Restricting the analysis to women, 4-ABP-Hb adducts were higher in cases than controls (Mann-Whitney P = 0.036) and the odds ratio (OR) for the presence/absence of adducts was 2.42 [95% confidence interval (95% CI), 1.18-4.98]. Moreover, the association of adducts with the individual cancer types was stronger in women than in the whole study population, although statistically significant only for leukemias (OR, 2.77; 95% CI, 1.06-7.20). The results provide some evidence that women may be more susceptible to environmental tobacco smoke, as suggested by their higher adduct levels. The most important finding of this prospective study is that, at least in women, 4-ABP-Hb adducts may help identify subjects at high risk of cancers related to environmental tobacco smoke exposure.

Biomarkers↗

PubMed2005

Fruit and vegetable consumption and risk of epithelial ovarian cancer: the European Prospective Investigation into Cancer and Nutrition.

OBJECTIVE: The association between consumption of fruit and vegetables and risk of ovarian cancer is still unclear from a prospective point of view. METHODS: Female participants (n = 325,640) of the European Prospective Investigation into Cancer and Nutrition study, free of any cancer at baseline, were followed on average for 6.3 years to develop ovarian cancer. During 2,049,346 person-years, 581 verified cases of primary, invasive epithelial ovarian cancer were accrued. Consumption of fruits and vegetables as well as subgroups of vegetables, estimated from validated dietary questionnaires and calibrated thereafter, was related to ovarian cancer incidence in multivariable hazard regression models. Histologic subtype specific analyses were done. RESULTS: Total intake of fruit and vegetables, separately or combined, as well as subgroups of vegetables (fruiting, root, leafy vegetables, cabbages) was unrelated to risk of ovarian cancer. A high intake of garlic/onion vegetables was associated with a borderline significant reduced risk of this cancer. The examination by histologic subtype indicated some differential effects of fruit and vegetable intake on ovarian cancer risk. CONCLUSION: Overall, a high intake of fruits and vegetables did not seem to protect from ovarian cancer. Garlic/onion vegetables may exert a beneficial effect. The study of the histologic subtype of the tumor warrants further investigation.

Adult↗

PubMed2005

Adipose organochlorine concentrations and risk of breast cancer among postmenopausal Danish women.

OBJECTIVE: Exposure to environmental organochlorines has been examined as a potential risk factor for human breast cancer with mixed results. Our purpose was to examine associations between organochlorines and the development of breast cancer in a large prospective study using stored adipose tissue. METHODS: We conducted a nested case-control study of 409 postmenopausal women who developed breast cancer and 409 controls selected from the 29,875 women enrolled in the Danish Diet, Cancer, and Health cohort between 1993 and 1997. We measured concentrations of 14 pesticides and 18 polychlorinated biphenyls in adipose tissue, collected upon enrollment, and estimated relative risk (RR) of breast cancer using conditional logistic regression. RESULTS: The results showed no higher risk of breast cancer among women with higher levels of any pesticides or polychlorinated biphenyls; the RR associated with the upper quartile of 1,1-dichloro-2, 2-bis(p-chlorophenyl)ethylene concentration was 0.7 [95% confidence interval (95% CI), 0.5-1.2] contrasting the lower quartile, and for the sum of polychlorinated biphenyls the similar risk was 1.1 (95% CI, 0.7-1.7). We observed a pattern of substantially lower risk of estrogen receptor-negative breast cancer in association with higher levels of most of the pesticides and polychlorinated biphenyls; the RR for the higher quartile of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene was 0.1 (95% CI, 0.0-0.5) and for the sum of polychlorinated biphenyls it was 0.3 (95% CI, 0.1-0.9). CONCLUSION: The results do not support that higher organochlorine body levels increase the risk of breast cancer in postmenopausal women. The interpretation of the inverse association for estrogen receptor-negative breast cancer is currently unclear.

Adipose Tissue↗

PubMed2004

Polymorphisms in genes involved in xenobiotic metabolism and lung cancer risk under the age of 60 years. A pooled study of lung cancer patients in Denmark and Norway.

The genetic susceptibility hypothesis has been used to explain why only a minority of smokers develop lung cancer. Only few studies have studied the role of polymorphisms in phase-I and II metabolizing genes, among young lung cancer patients. We have pooled the individual data of three studies from Denmark and Norway, including 320 patients diagnosed with non-small cell lung cancer at age 59 or below, and 618 age and gender matched controls. A questionnaire was used to determine relevant demographic and lifestyle characteristics, and polymorphisms in following genotypes were determined GSTM1, GSTM3, GSTP1, GSTT1, GPX1, MPO, NQO1 and NAT2. Based on the literature, the alleles of the genotypes were categorised as high- or low-risk alleles. No individual effect of the genotypes was found on the risk of lung cancer. Given a smoking exposure, the presence of high-risk alleles (or phenotypes) was generally found to increase the risk of lung cancer, although the effect modification did not reach statistical significance. A pattern of stronger protective effect was observed in carriers of more than one allele associated with lower risk of lung cancer, and a higher risk of lung cancer in carriers of one or more alleles associated with higher risk of lung cancer, but the results did not reach statistical significance. The effect modification was generally strongest at lower levels of smoking.

Adult↗

PubMed2004

Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer And Nutrition (EPIC).

The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort-wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow-up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size-breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all ptrend < or = 0.002); obese women (BMI > 30) had a 31% excess risk compared to women with BMI < 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00-1.16) in premenopausal and 1.10 (95% CI 1.05-1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (ptrend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist-hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer.

Abdomen↗

PubMed2004

Amount of DNA in plasma and cancer risk: a prospective study.

Levels of plasma DNA concentrations in cancer patients have been shown to be higher than the plasma DNA concentrations found in healthy subjects. The value of plasma DNA levels for development of neoplastic or pulmonary disease was evaluated in a large prospective study. Plasma samples (n = 1,184) were analyzed from 776 controls, 359 cases of cancer (lung, bladder, oral cavity, pharynx, larynx, leukemia) and 49 deaths from chronic obstructive pulmonary disease (COPD), including never smokers and ex-smokers, from 9 countries across Europe. The amount of plasma DNA was variable across the European Prospective Investigation into Cancer and Nutrition (EPIC) centers. High DNA concentrations in some centers might be due to the type of population recruited and/or the treatment of the samples. An elevated and statistically significant odds ratio (OR) was found for COPD deaths (OR = 2.53; 95% CI = 1.06-6.02), while nonsignificant increased ORs were present for oral cancers, cancers of the pharynx and larynx and leukemia. When the analyses were stratified by time since recruitment (below or above 36 months), the increased ORs were limited to the more recent period of recruitment, i.e., a time elapsed between blood drawing and disease onset lower than 36 months. This was particularly true for COPD deaths (OR = 12.7; 95% CI = 1.57-103) and leukemia (OR = 2.37; 95% CI = 1.20-4.67).

Adult↗

PubMed2004

XRCC3 polymorphisms and risk of lung cancer.

In a nested case-cohort study, we have investigated the occurrence of lung cancer in relation to polymorphisms in the double strand DNA repair gene XRCC3. Among 54,220 members of a Danish prospective cohort study aged 50-65 at entry, 265 lung cancer cases were identified and a sub-cohort, matched by age, sex and duration of smoking, comprising of 272 individuals was used for comparison. Ninety percent of both cases and comparison group were ever-smokers. Three previously studied polymorphisms; XRCC3 A4541G (5'UTR), A17893G (IVS5-14) and C18067T (T241M) were combined into haplotypes. The four most frequent haplotypes accounted for 98% of the genotypes. Homozygosity for the haplotype AAC was associated with a 4.91 times higher risk of lung cancer (confidence interval, 95% CI = 1.06-22.81) compared with the GAC haplotype. The polymorphism XRCC3 IVS6 C1571T was found to co-segregate with the AAC haplotype, and homozygous carriers of the variant T-allele had a 4.47 (CI = 1.34-14.96) times higher risk of lung cancer compared with homozygous carriers of the wild type allele. Our results indicate that XRCC3 IVS6 C1571T and the associated haplotype AAC are associated with relatively high risk of lung cancer.

Aged↗