The Role of Melanocortin‐1 Receptor Polymorphism in Skin Cancer Risk Phenotypes

We have examined melanocortin‐1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32–140) or weak r (OR = 5; 95% CI 3–11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild‐type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk.     

Association between family cancer history and risk of pancreatic cancer

PurposeFamily history of pancreatic adenocarcinoma is an established risk factor for the disease. However, associations of pancreatic cancer with other familial cancers are less clear. We analyzed data from the Queensland Pancreatic Cancer Study (QPCS), an Australian population-based case-control study, to investigate associations between family history of various cancer types and risk of pancreatic cancer.Materials and methodsOur study included 591 pancreatic cancer patients and 646 controls, all of whom self-reported the histories of cancer in their first-degree relatives. We used logistic regression to estimate adjusted odds ratios (ORs) and their 95% confidence intervals (CIs). Based on our results, we conducted a systematic literature review using the Medline (OVID) database to identify articles pertaining to the association between family history of melanoma and risk of pancreatic cancer. A meta-analysis including associations in five published studies, unpublished results from a study co-author and the QPCS results was then performed using the DerSimonian and Laird random-effects model.ResultsCases were more likely than controls to report a family history of pancreatic cancer (OR 2.20, 95% CI 1.16–4.19) and melanoma (OR 1.74, 95% CI 1.03–2.95), but not of breast, ovarian, respiratory, other gastrointestinal or prostate cancer. Meta-analysis of melanoma family history and pancreatic cancer risk yielded an OR of 1.22 (95% CI 1.00–1.51).ConclusionsOur results yield further evidence of increased risk of pancreatic cancer in those with family histories of the disease. We also provide suggestive evidence of an association between family history of melanoma and risk of pancreatic cancer.     

Asthma,allergy and the risk of prostate cancer: Results from the Montreal PROtEuS study

BackgroundThe few previous studies examining the association between asthma or allergy and prostate cancer (PCa) risk were inconclusive. This study aimed to evaluate these associations, and to explore in details the possible influence of current versus former allergic condition, age at onset, time since onset, and duration of each allergic condition.MethodsDetailed information on self-reported asthma and allergy was collected in the context of a large population-based case–control study conducted in Montreal, Canada. Study subjects included 1936 cases, diagnosed between 2005 and 2009, and 1995 population controls. Unconditional multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, ancestry and familial history of prostate cancer.ResultsThe ORs were 1.11 (95% CI: 0.89–1.40) and 0.98 (95% CI: 0.84–1.14) for ever reporting of asthma and allergy, respectively. These ORs did not substantially vary according to status (former or current), age at onset, time since onset, and duration of each allergic condition. PCa screening was not associated with allergic diseases reporting.ConclusionsOverall, our findings are in line with the absence of an association between a history of asthma or allergy, and PCa risk.     

The role of melanocortin-1 receptor polymorphism in skin cancer risk phenotypes

We have examined melanocortin-1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32-140) or weak r (OR = 5; 95% CI 3-11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild-type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk.     

Association between Glaucoma and Obstructive Sleep Apnea Syndrome: A Meta-Analysis and Systematic Review

BackgroundObstructive sleep apnea syndrome (OSAS) is a common disease that increases the risk of diabetes, heart disease, and stroke. However, studies of an association between OSAS and glaucoma neuropathy have reported controversial findings.ObjectiveThe main purpose of this study was to evaluate whether a significant association exists between OSAS and glaucoma by performing a meta-analysis of previous studies.MethodsA comprehensive literature search using the PubMed and Embase databases was performed to identify cross-sectional, case-control, and cohort studies related to the topic. We estimated a pooled odds ratio (OR) for the association between OSAS and glaucoma, by a fixed- or random-effects model.ResultsIn total, 16 studies with 2,278,832 participants met the inclusion criteria: one retrospective cohort study reported an adjusted hazard ratio of glaucoma of 1.67 (95% CI = 1.30–2.17). Using a fixed-effects model, the pooled OR of six case-control studies was 1.96 (95% CI = 1.37 2.80). A significant association was also identified in a meta-analysis of nine cross-sectional studies using a random-effects model, which showed a pooled OR of 1.41 (95% CI = 1.11 1.79). However, the reported pooled estimates for case control studies and cross-sectional studies were based on unadjusted ORs.ConclusionsOur results suggest that OSAS is associated with the prevalence of glaucoma. However, this result was based only on unadjusted estimates. Prospective cohort studies designed to take into consideration potential confounders, or examination of data from interventional trials to determine whether a reduction in OSAS status is associated with a reduced incidence of glaucoma, are needed to clarify whether OSAS is an independent risk factor for glaucoma.     

Hysterectomy and risk of epithelial ovarian cancer by histologic type,endometriosis, and menopausal hormone therapy

BackgroundThis nationwide, register-based case-control study investigated the association between hysterectomy and risk of epithelial ovarian cancer according to histology and by history of endometriosis and menopausal hormone therapy (MHT) use.MethodsFrom the Danish Cancer Registry, all women registered with epithelial ovarian cancer at age 40–79 years during 1998–2016 were identified (n = 6738). Each case was sex- and age-matched to 15 population controls using risk-set sampling. Information on previous hysterectomy on benign indication and potential confounders was retrieved from nationwide registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for the association between hysterectomy and ovarian cancer according to histology, endometriosis, and use of MHT.ResultsHysterectomy was not associated with risk of epithelial ovarian cancer overall (OR=0.99; 95% CI 0.91 –1.09) but was associated with reduced risk of clear cell ovarian cancer (OR=0.46; 95% CI 0.28–0.78). In stratified analyses, decreased ORs associated with hysterectomy were seen in women with endometriosis (OR=0.74; 95% CI 0.50–1.10) and in non-users of MHT (OR=0.87; 95% CI 0.76–1.01). In contrast, among long-term MHT users, hysterectomy was associated with increased odds for ovarian cancer (OR=1.20; 95% CI 1.03–1.39).ConclusionHysterectomy was not associated with epithelial ovarian cancer overall but with reduced risk of clear cell ovarian cancer. Our findings may suggest a reduced risk of ovarian cancer after hysterectomy in women with endometriosis and in MHT non-users. Interestingly our data pointed to an increased ovarian cancer risk associated with hysterectomy among long-term users of MHT.     

Alcohol consumption and lung cancer risk: A pooled analysis from the International Lung Cancer Consortium and the SYNERGY study

BackgroundThere is inadequate evidence to determine whether there is an effect of alcohol consumption on lung cancer risk. We conducted a pooled analysis of data from the International Lung Cancer Consortium and the SYNERGY study to investigate this possible association by type of beverage with adjustment for other potential confounders.MethodsTwenty one case-control studies and one cohort study with alcohol-intake data obtained from questionnaires were included in this pooled analysis (19,149 cases and 362,340 controls). Adjusted odds ratios (OR) or hazard ratios (HR) with corresponding 95% confidence intervals (CI) were estimated for each measure of alcohol consumption. Effect estimates were combined using random or fixed-effects models where appropriate. Associations were examined for overall lung cancer and by histological type.ResultsWe observed an inverse association between overall risk of lung cancer and consumption of alcoholic beverages compared to non-drinkers, but the association was not monotonic. The lowest risk was observed for persons who consumed 10–19.9 g/day ethanol (OR vs. non-drinkers = 0.78; 95% CI: 0.67, 0.91), where 1 drink is approximately 12–15 g. This J-shaped association was most prominent for squamous cell carcinoma (SCC). The association with all lung cancer varied little by type of alcoholic beverage, but there were notable differences for SCC. We observed an association with beer intake (OR for ≥20 g/day vs nondrinker = 1.42; 95% CI: 1.06, 1.90).ConclusionsWhether the non-monotonic associations we observed or the positive association between beer drinking and squamous cell carcinoma reflect real effects await future analyses and insights about possible biological mechanisms.     

Job strain and risk of esophageal and cardia cancers

BackgroundFew studies have investigated work-related stress in relation to esophageal or cardia cancers.MethodsOur nationwide Swedish population-based case-control study included 189 and 262 esophageal and cardia adenocarcinoma cases respectively, 167 esophageal squamous-cell carcinoma cases and 820 controls. We derived each study participant's occupation of longest duration from occupational histories and applied a psychosocial job-exposure matrix. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression, in multivariable models.ResultsJob strain was positively associated with risk of esophageal adenocarcinoma (OR 3.2, 95% CI 1.0–9.8) and squamous-cell carcinoma (OR 4.0, 95% CI 1.6–10.5), but not with cardia adenocarcinoma. No associations regarding demands, control, social support or iso strain were observed, except for a positive association between high control and risk of esophageal squamous-cell carcinoma (OR 1.5, 95% CI 1.0–2.3).ConclusionJob strain seems to increase the risk of both histological types of esophageal cancer.     

Coffee and tea consumption during pregnancy and risk of childhood acute myeloid leukemia: A Childhood Leukemia International Consortium (CLIC) study

BackgroundDietary habits during pregnancy have been inconsistently linked to childhood acute myeloid leukemia (AML), given the putative intrauterine onset of the disease as a result of triggering events during the critical period of fetal hematopoiesis. We investigated the potential association of maternal coffee and tea consumption during pregnancy with childhood AML risk, pooling primary data from eight case-control studies participating in the Childhood Leukemia International Consortium.MethodsInformation on coffee and/or tea consumption was available for 444 cases and 1255 age- and sex-matched controls, on coffee consumption for 318 cases and 971 controls and on tea consumption for 388 cases and 932 controls. Categories for cups of daily coffee/tea consumption were created in order to explore potential dose-response associations. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression.ResultsAssociations were found neither in the analysis on coffee or tea nor in the analysis on coffee only consumption (any versus no). A positive association with increasing coffee intake was observed (>1 cup per day; OR: 1.40, 95% CI: 1.03–1.92, increment of one cup per day; OR: 1.18, 95% CI: 1.01–1.39). No associations were observed with tea consumption. Interaction analyses showed non-significant associations between coffee/tea and smoking. Hyperdiploidy was inversely associated with tea consumption, with other cytogenetic markers having no association with coffee/tea.ConclusionGiven the widespread consumption of caffeinated beverages among pregnant women, our finding is of important public health relevance, suggesting adverse effects of maternal coffee consumption during pregnancy in the offspring.     

High parental occupational social contact and risk of childhood hematopoietic,brain and bone cancers

BackgroundThe etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers.MethodsWe examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (<17 years, diagnosed 1973–2012) and 358,100 age-matched controls. We examined the risks of leukemia, lymphoma, CNS and bone cancer related to high occupational social contact from (1) conception to birth and (2) birth to diagnosis.ResultsAcute lymphoblastic leukemia (ALL) and bone cancer were inversely associated with high maternal social contact from conception to birth (OR: 0.86, 95% CI: 0.67–1.10) and birth to diagnosis (OR: 0.54, 95% CI: 0.34–0.86). Children of fathers with high social contact from birth to diagnosis had an increased risk of bone cancers, particularly in rural areas (OR: 1.65, 95% CI: 1.03–2.63). Parental social contact was associated with increased risk of astrocytoma, with strongest associations found in first-born children (maternal: OR: 1.54, 95% CI: 1.02–2.32; paternal: OR: 1.82, 95% CI: 1.05–3.17).ConclusionOur results support the notion of a role of infections for some cancer types.     

Body mass index and the risk of head and neck cancer in the Chinese population

ObjectiveTo investigate potential associations between body mass index (BMI) and head and neck cancer (HNC) risk in an East Asian population.MethodsWe conducted a hospital-based multicenter case-control study in East Asia including 921 cases and 806 controls. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CI) for HNC risks by using logistic regression, adjusting on potential confounders.ResultsCompared to normal BMI at interview (18.5–<25 kg/m²), being underweight (BMI < 18.5 kg/m²) was associated with a higher HNC risk (OR = 2.71, 95% CI 1.40–5.26). Additionally, obesity (BMI > 30 kg/m²) was associated with a lower HNC risk (OR = 0.30, 95% CI 0.16–0.57). Being underweight at age 20 was also associated with an increased risk of HNC. However, being underweight at 5 years or 2 years before interview was not associated with a higher risk of HNC.ConclusionWe observed an inverse association between BMI and HNC risk, which is consistent with previous studies in other geographic regions. Being underweight at age 20 was also associated with a higher risk of HNC, suggesting that reverse causality was not the main source of the association.     

ABO Blood Group and Incidence of Skin Cancer

Background

Previous studies have examined the association between ABO blood group and the risk of some malignancies. However, no prospective cohort study to date has examined the association between ABO blood group and the risk of skin cancer.

Methodology/Principal Findings

Using two large cohorts in the US, we examined ABO blood type and incidence of skin cancer, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC). We followed up study participants (70,650 female nurses and 24,820 male health professionals) on their diagnosis of incident skin cancer from cohort baseline (1976 in women and 1986 in men) until 2006. Study participants reported their blood type in 1996 in both cohorts. During the follow-up, 685 participants developed melanoma, 1,533 developed SCC and 19,860 developed BCC. We used Cox proportional hazards models to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of each type of skin cancer. We observed that non-O blood group (A, AB, and B combined) was significantly associated with a decreased risk of non-melanoma skin cancer overall. Compared to participants with blood group O, participants with non-O blood group had a 14% decreased risk of developing SCC (multivariable HR: 0.86; 95% CI: 0.78, 0.95) and a 4% decreased risk of developing BCC (multivariable HR: 0.96; 95% CI: 0.93, 0.99). The decreased risk of melanoma for non-O blood group was not statistically significant (multivariable HR: 0.91; 95% CI: 0.78, 1.05).

Conclusion/Significance

In two large independent populations, non-O blood group was associated with a decreased risk of skin cancer. The association was statistically significant for non-melanoma skin cancer. Additional studies are needed to confirm these associations and to define the mechanisms by which ABO blood type or closely linked genetic variants may influence skin cancer risk.     

Association of iron metabolism markers,socioeconomic and lifestyle factors with endometriosis: A cross-sectional study

BackgroundEvidence on the link between iron metabolism markers and endometriosis is limited. We aimed to investigate the associations of iron metabolism markers, including serum ferritin level and transferrin saturation, with endometriosis.MethodsThis study involved 6551 participants from the National Health and Nutrition Examination Survey (NHANES). Univariable and multivariable logistic regression analyses were used to examine the linear relationships between iron metabolism markers and endometriosis. Furthermore, restricted cubic splines were used to identify the non-linear dose-response associations.ResultsUnivariable analysis showed that the factors associated with endometriosis included age, race, education level, and smoking status. In multivariable model, compared with lowest quartile, highest quartile of serum ferritin level was positively associated with endometriosis (OR: 2.11, 95% confidence intervals [CI]: 1.31, 3.40, P = 0.004), and third quartile of transferrin saturation positively associated with endometriosis (OR: 1.55, 95% CI: 1.05, 2.29, P = 0.033). The restricted cubic splines showed the non-linear (inverted U-shape) associations between serum ferritin level and transferrin saturation and endometriosis (all P for non-linear＜0.01), indicating that the ORs of endometriosis increased with serum ferritin level and transferrin saturation up to the turning point and thereafter the ORs of endometriosis did not significantly increase with the increasing serum ferritin and transferrin saturation.ConclusionsOur findings suggests that serum ferritin level and transferrin saturation were positively associated with endometriosis. Serum ferritin and transferrin saturation may be an important marker for endometriosis. Future prospective and longitudinal studies are necessary to better understand these findings.     

Demographic,social and lifestyle risk factors for cancer registry-notified cancer of unknown primary site (CUP)

BackgroundLittle is known about the risk factors for cancer of unknown primary site (CUP). We examined the demographic, social and lifestyle risk factors for CUP in a prospective cohort of 266,724 people aged 45 years and over in New South Wales, Australia.MethodsBaseline questionnaire data were linked to cancer registration, hospitalisation, emergency department admission, and mortality data. We compared individuals with incident cancer registry-notified CUP (n = 327) to two sets of controls randomly selected (3:1) using incidence density sampling with replacement: (i) incident cancer registry-notified metastatic cancer of known primary site (n = 977) and (ii) general cohort population (n = 981). We used conditional logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).ResultsIn a fully adjusted model incorporating self-rated overall health and comorbidity, people diagnosed with CUP were more likely to be older (OR 1.05, 95% CI 1.04–1.07 per year) and more likely to have low educational attainment (OR 1.77, 95% CI 1.24–2.53) than those diagnosed with metastatic cancer of known primary. Similarly, compared to general cohort population controls, people diagnosed with CUP were older (OR 1.10, 95% CI 1.08–1.12 per year), of low educational attainment (OR 1.69, 95% CI 1.08–2.64), and current (OR 3.42, 95% CI 1.81–6.47) or former (OR 1.95, 95% CI 1.33–2.86) smokers.ConclusionThe consistent association with educational attainment suggests low health literacy may play a role in CUP diagnosis. These findings highlight the need to develop strategies to achieve earlier identification of diagnostically challenging malignancies in people with low health literacy.     

Exposure to Ionizing Radiation during Dental X-Rays Is Not Associated with Risk of Developing Meningioma: A Meta-Analysis Based on Seven Case-Control Studies

BackgroundMany observational studies have found that exposure to dental X-rays is associated with the risk of development of meningioma. However, these findings are inconsistent. We conducted a meta-analysis to assess the relationship between exposure to dental X-rays and the risk of development of meningioma.MethodsThe PubMed and EMBASE databases were searched to identify eligible studies. Summary odds ratio (OR) estimates and 95% confidence intervals (95% CIs) were used to compute the risk of meningioma development according to heterogeneity. Subgroup and sensitivity analyses were performed to further explore the potential heterogeneity. Finally, publication bias was assessed.ResultsSeven case-control studies involving 6,174 patients and 19,459 controls were included in the meta-analysis. Neither exposure to dental X-rays nor performance of full-mouth panorex X-rays was associated with an increased risk of development of meningioma (overall: OR, 0.97; 95% CI, 0.70–1.32; dental X-rays: OR, 1.05; 95% CI, 0.89–1.25; panorex X-rays: OR, 1.01; 95% CI, 0.76–1.34). However, exposure to bitewing X-rays was associated with a slightly increased risk of development of meningioma (OR, 1.73; 95% CI, 1.28–2.34). Similar results were obtained in the subgroup and sensitivity analyses. Little evidence of publication bias was observed.ConclusionBased on the currently limited data, there is no association between exposure to dental X-rays and the risk of development of meningioma. However, these results should be cautiously interpreted because of the heterogeneity among studies. Additional large, high-quality clinical trials are needed to evaluate the association between exposure to dental X-rays and the risk of development of meningioma.     

The association between dietary intakes of methionine,choline and betaine and breast cancer risk: A systematic review and meta-analysis

Background and aimThis study evaluates the associations between dietary intakes and circulating blood levels of methionine, choline or betaine and breast cancer risk, which remains currently unclear.MethodsSystematic searches for observational epidemiological studies were performed of the MEDLINE, Embase, and Web of Science databases through July, 2022. Two review authors independently screened titles and abstracts against the eligibility criteria at a first stage, and screened full texts of potentially eligible records at a second stage, followed by data extraction from qualified studies. Quality of evidence was assessed using the Newcastle-Ottawa scale quality assessment tool. Risk estimates were calculated using random-effects meta-analysis.ResultsIn total, 21 studies were selected for qualitative analyses and 18 studies were included in the meta-analyses. Random-effects analysis combining prospective cohort (N = 8) or case–control studies (N = 10) showed little evidence of an association between dietary intake of methionine or betaine and the risk of breast cancer. However, inconclusive evidence for a significant inverse association between choline intake and breast cancer risk was found in case–control studies (odds ratio [OR] estimates for highest vs. lowest intakes = 0.38; 95 % CI: 0.16–0.86) but not in prospective cohort studies (hazard ratio [HR] estimates for highest vs. lowest intakes = 1.01; 95 % CI: 0.92–1.12).ConclusionThis study did not suggest an effect of dietary intake of methionine, choline, nor betaine on breast cancer risk, mainly due to the lack of precision of the combined risk estimates as few studies are available. To overcome this uncertainty, more well-designed studies with relevant individual-level covariates are needed.     

Lack of association between methylenetetrahydrofolate reductase gene A1298C polymorphism and breast cancer susceptibility

Published data on the association between methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR A1298C polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (AC vs. AA, CC vs. AA), dominant model (CC+AC vs. AA), and recessive model (CC vs. AC+AA), respectively. A total of 26 studies including 12,244 cases and 15,873 controls were involved in this meta-analysis. Overall, no significant associations were found between MTHFR A1298C polymorphism and breast cancer risk when all studies pooled into the meta-analysis (AC vs. AA: OR=0.99, 95% CI 0.94-1.05; CC vs. AA: OR 0.99, 95% CI 0.90-1.09; dominant model: OR=0.99, 95% CI 0.95-1.04; and recessive model: OR=0.98, 95% CI 0.90-1.08). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MTHFR A1298C polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.     

Pre-diagnostic plasma 25-hydroxyvitamin D levels and risk of non-melanoma skin cancer in women

Background

Recent reports have shown that vitamin D status was inversely associated with the risk of various cancers. However, few studies examined the association between vitamin D levels and risk of skin cancer.

Methods

We prospectively evaluated the association between baseline plasma 25(OH)D levels and the risk of incident squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) among 4,641 women from the Nurses’ Health Study (NHS) and the NHS II with 510 incident BCC cases and 75 incident SCC cases. We used multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Plasma 25(OH)D levels were positively associated with risk of BCC after adjusting for age at blood draw, season of blood draw, lab batch, hair color, burning tendency, the number of sunburns, and ultra-violet B flux of residence at blood collection. Women in the highest quartile of 25(OH)D had more than 2-fold increased risk of BCC compared with women in the lowest quartile (OR = 2.07, 95% CI = 1.52–2.80, P for trend <0.0001). We also found a significantly positive association between plasma 25(OH)D levels and SCC risk after adjusting for the same covariates (OR, highest vs. lowest quartile  = 3.77, 95% CI = 1.70–8.36, P for trend  = 0.0002).

Conclusion

In this prospective study of women, plasma vitamin D levels were positively associated with non-melanoma skin cancer risk. Considering that most circulating vitamin D is due to sun exposure, the positive association between plasma vitamin D and non-melanoma skin cancer is confounded by sun exposure. Our data suggest that one-time measurement of plasma vitamin D levels may reasonably reflect long-term sun exposure and predict the risk of non-melanoma skin cancer.     

Relationships between serum iron and liver diseases in nutrition intervention trials: A nested case-control study

BackgroundSerum iron is associated with the risk of several diseases. However, limited prospective studies have been performed between serum iron and the subsequent risk of chronic liver disease (CLD) and primary liver cancer (PLC) incidence.MethodsWe performed a nested case-control study using data from the Linxian Nutrition Intervention Trials among participants who developed PLC incidence or died from CLD over 22-years of follow-up. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) to estimate the risk of PLC incidence or CLD death in different quintile of baseline serum iron using logistic regression.ResultsIndividuals with serum iron in the highest quintile, compared to those in the second quintile (the reference), had an increased risk of CLD mortality (OR=2.02, 95% CI=1.27–3.27, P_trend=0.011). The association was stronger among HCV-positive participants (P_interaction=0.005). For PLC incidence, the risk estimates were above one, but not statistically significant (all P > 0.05).ConclusionsA significant positive association was found between serum iron and the risk of CLD-related mortality, especially in HCV-positive subjects. Our results suggest that serum iron plays a risk role in CLD death but not in PLC incidence.     

Lifestyle-Related Factors and Atopy in Seven Danish Population-Based Studies from Different Time Periods

Background

The prevalence of allergic respiratory disease tends to increase in populations that adopt the so-called Westernized lifestyle. We investigated the association between atopy and several possible lifestyle-related factors in seven Danish population-based studies.

Methods

A total of 20048 persons participated in the seven studies. We used logistic regression to analyse the associations between possible determinants and atopy defined as serum specific IgE or skin prick test positivity against inhalant allergens. Associations were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). In addition, individual participant data meta-analyses were performed.

Results

Atopy was significantly associated with younger age (OR per 1 year increase in age: 0.97; 95% CI: 0.97, 0.98); male sex (OR for males versus females: 1.34; 95% CI: 1.24, 1.45), heavy drinking (OR for heavy drinkers versus light drinkers: 1.15; 95% CI: 1.04, 1.27), never smoking (OR for current versus never smokers: 0.73; 95% CI: 0.67, 0.80), and higher educational level (OR for educated versus uneducated: 1.27; 95% CI: 1.15, 1.41). Atopy was not associated with blood pressure, serum total cholesterol, physical activity or body mass except in women only, where we found a positive association (OR for obese vs. normal weight: 1.18; 95% CI: 1.00, 1.39) with p_trend = 0.032.

Conclusions

Of interest for preventive purposes, we found that atopy was associated with some of the reversible lifestyle-related factors that characterize a Westernized lifestyle.