Risk factors associated with neuroendocrine tumors: A U.S.-based case-control study

Carcinoids are rare neuroendocrine tumors (NETs); however, their incidence has significantly increased in the United States over the past 30 years. Little is known about the epidemiology of these cancers and their associated risk factors. We evaluated the independent effects of multiple risk factors associated with NETs arising at 5 disease sites (small intestine, stomach, lung, pancreas and rectum). We conducted a retrospective, hospital-based, case-control study involving 740 patients with histologically confirmed NETs and 924 healthy controls. Information on different risk factors was collected, and unconditional logistic regression analysis was used to determine adjusted odds ratios (AORs) and 95% confidence interval (CI) by the maximum-likelihood method. Smoking and alcohol consumption were not associated with NETs development in either men or women. However, a family history of cancer was a significant risk factor for all NETs. A long-term history of diabetes mellitus was a significant risk factor for gastric NETs (AOR = 5.6; 95% CI, 2.1-14.5), particularly in women (AOR = 8.4; 95% CI, 1.9-38.1). Diabetes modified the risk among women with a positive family history of cancer for the development of gastric NETs (AOR = 52.2; 95% CI, 5.5-491.5). Our results suggest that the risk of NETs may mostly explained by genetic factors. The increased risk of gastric NETs in women with both diabetes and a positive family history of cancer suggest that women may have a greater genetic susceptibility to NETs than men.     

Long-term overweight and weight gain in early adulthood in association with risk of endometrial cancer

Long-term overweight and substantial weight gain over adulthood are known risk factors of endometrial cancer, but the timing of weight gain in relation to risk and the effect of weight change on age at diagnosis remain unclear. A population-based case-control study was conducted to evaluate the long-term effect of body weight on endometrial cancer risk. The study enrolled 668 incident cases and 674 population controls. Anthropometric features in each decade of adult life were ascertained through in-person interview and analyzed for their associations with endometrial cancer using unconditional logistic regression. As expected, high body mass index (BMI) was significantly associated with increased risk. Women who were overweight or obese at the time of interview had adjusted odds ratios of 1.54 (95%CI 1.13-2.10) and 4.76 (95%CI 3.50-6.49), respectively, compared to women of normal weight. Similar associations were observed for BMI assessed at each decade of adult life. More importantly, women who were overweight (BMI ≥ 25) in their 20s or 30s and maintained the overweight throughout life had significantly higher risk than those who became overweight at ages 40s or 50s. Women with substantial weight gain (≥35%) in early adulthood (age 20s) developed the disease 10 years earlier than those without such weight change in early life. These observations further confirm the critical link between body weight and development of endometrial cancer.     

Lifetime adult weight gain, central adiposity, and the risk of pre- and postmenopausal breast cancer in the Western New York exposures and breast cancer study

While there are quite consistent data regarding associations of body weight and postmenopausal breast cancer, there are now accumulating data that would indicate that weight gain in adult life is more predictive of risk than absolute body weight. There is, however, little known about the relative impact of timing of weight gain in adult life as well as other characteristics of the weight and breast cancer association that might provide insight into the mechanism of the observation. We conducted a population-based case control study of breast cancer (1996-2001), the Western New York Exposures and Breast Cancer Study. Included were 1,166 women with primary, histologically confirmed, incident breast cancer and 2,105 controls frequency-matched on age, race and county of residence. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. We found increased risk of breast cancer associated with lifetime adult weight gain among post- but not premenopausal women, and there was a 4% increase in risk for each 5 kg increase in adult weight. Further there was a tendency toward a stronger association for those with higher waist circumference and those with positive estrogen or progesterone status, and who had never used HRT. We also found an association with risk for weight gain since first pregnancy and for weight gain between the time of the first pregnancy and menopause, independent of body mass index and lifetime adult weight gain. Our results suggest that there are time periods of weight gain that have greater impact on risk, and that central body fat, receptor status and hormone replacement therapy may all affect the observed association.     

Association between plasma cholesterol and prostate cancer in the PSA era

We previously found that statin users had a lower risk of advanced and possibly high-grade prostate cancer compared with nonusers. We hypothesize that statins' effects on cholesterol synthesis may explain those findings because prostate cancer cells exhibit cholesterol dysregulation. Thus, we investigated whether low plasma cholesterol is associated with prostate cancer overall and by stage and grade. Participants were drawn from the 18,018 members of the Health Professionals Follow-Up Study who provided blood in 1993-1995. We ascertained 698 incident cases through January 2000. Controls were 698 men who had a PSA test and were matched to cases. Plasma cholesterol was measured enzymatically. Conditional logistic regression was used to estimate multivariable ORs and 95% CIs of total, clinically organ-confined (n = 518), advanced (T3b or worse; n = 61), low-grade (Gleason sum < 7; n = 386) and high-grade (Gleason sum > or = 7, n = 247) disease. Low cholesterol (<25th percentile vs. > or =25th percentile) was not associated with total (OR = 0.93, 95% CI: 0.72-1.20), organ-confined (OR = 0.87, 95% CI: 0.64-1.18) or low-grade (OR = 1.06, 95% CI: 0.75-1.51) disease. However, men with low cholesterol had a lower risk of high-grade disease (OR = 0.61, 95% CI: 0.39-0.98), especially if organ-confined (OR = 0.54, 95% CI: 0.29-0.99). The association for advanced disease appeared inverse, but number of cases was small (OR = 0.42, 95% CI: 0.13-1.36). Associations remained after excluding cholesterol-lowering drug users. These results coupled with prior statin findings suggest that mechanistic studies on cholesterol metabolism should be pursued to understand a possible target for preventing poorly differentiated prostate cancers.     

Etiologic factors associated with p53 immunostaining in cutaneousmalignant melanoma

Findings from a case-control study of cutaneous malignant melanoma (CMM) in Queensland, Australia, suggest that melanomas exhibiting p53 immunostaining possess different risk factors from those of other melanomas. To further explore this hypothesis, a case-only analysis of risk factors for p53 immunostaining with anti-p53 MAb DO-7 was undertaken in 523 people diagnosed with CMM in Canada and Australia. Phenotypic factors and past sun exposure were measured using a self-administered questionnaire and telephone interview. The presence of strong p53 staining (>10% of cell nuclei positively stained vs. <1% staining) was positively associated with some indicators of high cumulative sun exposure: lentigo maligna melanoma subtype (OR = 3.2 vs. superficial spreading subtype), melanoma location on the head and neck (OR = 2.8 vs. back), histopathologic evidence of solar elastosis (OR = 2.1) and previous diagnosis of nonmelanoma skin cancer (OR = 2.4). Strong staining was negatively associated with high nevus density on the back (OR = 0.2 for >25 nevi vs. 0-3 nevi) and histologic evidence of a coexisting nevus (OR = 0.3). Other factors associated with strong p53 immunostaining include greater Breslow thickness (OR = 7.4 for >4.00 vs. <0.76 mm), male sex (OR = 2.2) and dense freckling (OR = 6.6 vs. few freckles). Of these, thickness, male sex, dense freckling, low nevus density on the back, histologic subtype and history of nonmelanoma skin cancer appeared to be independently associated with strong p53 staining. Our findings are consistent with the Queensland study in suggesting that variables indicating high accumulated sun exposure are positively associated with p53 staining and that an increased number of nevi is positively associated with its absence; they may reflect etiologic and pathogenetic heterogeneity in melanoma.     

Asthma status is associated with decreased risk of aggressive urothelial bladder cancer

Previous studies suggested an association between atopic conditions and specific cancers. The results on the association with urothelial bladder cancer (UBC) are scarce and inconsistent. To evaluate the association between asthma and risk of UBC, we considered 936 cases and 1,022 controls from the Spanish Bladder Cancer/EPICURO Study (86% males, mean age 65.4 years), a multicenter and hospital‐based case–control study conducted during 1998–2001. Participants were asked whether they had asthma and detailed information about occupational exposures, smoking habits, dietary factors, medical conditions and history of medication was collected through face‐to‐face questionnaires performed by trained interviewers. Since asthma and UBC might share risk factors, association between patients' characteristics and asthma was studied in UBC controls. Association between UBC and asthma was assessed using logistic regression unadjusted and adjusted for potential confounders. The complex interrelationships, direct and mediating effect of asthma on UBC, were appraised using counterfactual mediation models. Asthma was associated with a reduced risk of UBC (odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.37, 0.79) after adjusting for a wide range of confounders. No mediating effect was identified. The reduced risk associated with asthma was restricted to patients with high‐risk non‐muscle invasive (OR = 0.25, 95%CI 0.10, 0.62) and muscle invasive UBC (OR = 0.32, 95%CI 0.15, 0.69). Our results support that asthma is associated with a decreased risk of UBC, especially among aggressive tumors. Further work on the relationship between asthma and other atopic conditions and cancer risk should shed light on the relationship between immune response mechanisms and bladder carcinogenesis.     

Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk

Background:

Bisphosphanates are used primarily for the prevention and treatment of osteoporosis, and are also indicated for osseous complications of malignancy. In addition to their bone resorption properties, the most commonly used nitrogen-containing bisphosphonate compounds also inhibit protein prenylation, and thus may exert anti-tumour properties.

Methods:

To evaluate whether the use of these drugs may be associated with cancer, specifically breast cancer, we conducted a population-based case–control study in Wisconsin from 2003 to 2006. Participants included 2936 incident invasive breast cancer cases and 2975 population controls aged <70 years. Bisphosphonate use and potential confounders were assessed by interview.

Results:

Using multivariable logistic regression, the odds ratio for breast cancer in current bisphosphonate users compared with non-users was 0.67 (95% confidence interval 0.51–0.89). Increasing duration of use was associated with a greater reduction in risk (P-trend=0.01). Risk reduction was observed in women who were not obese (P-interaction=0.005).

Conclusion:

These results are suggestive of an additional benefit of the common use of bisphosphonates, in this instance, the reduction in breast cancer risk.     

Matrix metalloproteinase polymorphisms are associated with bladder cancer invasiveness.

PURPOSE: Matrix metalloproteinases (MMP) promote tumor invasion and alter microenvironment. MMP levels are elevated in bladder cancer patients correlating with more advanced stage. We tested whether polymorphisms in MMP genes modify the risk of bladder cancer invasiveness and whether smoke exposure modifies this risk. EXPERIMENTAL DESIGN: Using a case-only study, we examined the association of 11 single-nucleotide polymorphisms and one microsatellite polymorphism in MMP genes MMP1, MMP2, MMP3, MMP8, MMP9, and MMP12 with the risk of invasive bladder cancer in 243 Caucasian patients with muscle invasive compared with 315 Caucasian patients with superficial disease. RESULTS: The MMP9 microsatellite >or=24 CA repeat and MMP12 -82 G alleles were associated with a higher risk of bladder cancer invasiveness [odds ratio (OR), 3.10; 95% confidence interval (95% CI) 1.17-8.23 and OR, 1.50; 95% CI, 1.00-2.28, respectively]. Ever smokers with the MMP9 >or=24 CA repeat allele had a 5.16-fold (95% CI, 1.56-17.1) increased risk of invasiveness compared with wild-type never smokers. Ever smokers with the MMP12 G allele also had an increased risk of bladder cancer invasiveness (OR, 2.32; 95% CI, 1.30-4.12). CONCLUSIONS: Our results suggest that genetic changes in MMPs are associated with the development of invasive bladder cancer.     

Allergies are associated with reduced pancreas cancer risk: A population-based case-control study in Ontario, Canada

Pancreatic adenocarcinoma is one of the deadliest cancers with mortality rates almost equaling incidence rates. Each year, approximately 3,500 Canadians are diagnosed with this disease. Although somewhat inconsistent, epidemiological studies have found that allergies are associated with a reduced pancreas cancer risk while there appears to be no association with asthma. These associations were evaluated in a population-based case-control study conducted in Ontario. Incident cases of pancreatic adenocarcinoma, identified through the Ontario Cancer Registry (OCR), and diagnosed April 1, 2003 to June 1, 2006, were recruited by the Ontario Pancreas Cancer Study (OPCS). Controls were recruited from the Ontario Familial Colorectal Cancer Registry (OFCCR). Data on 276 cases and 378 controls were available for the current study. Multivariable logistic regression analysis was used to obtain age-adjusted odds ratio (AOR) estimates. Ever having allergies or hayfever was associated with reduced pancreas cancer risk (OR = 0.43, 95% confidence interval (CI): 0.29-0.63). There was no association observed between a history of asthma and pancreas cancer risk. Findings are of great importance to understanding the biological mechanisms involved in pancreas cancer development.     

Flavonoids and ovarian cancer risk: A case-control study in Italy

Flavonoids belong to a vast group of polyphenols widely distributed in all foods of plant origin. Because of their antioxidant, antimutagenic and antiproliferative properties, they have been hypothesized to contribute to the favorable effects of fruit and vegetables against cancer. The aim of this study is to investigate the relation of 6 classes of flavonoids (flavan-3-ols, flavanones, flavonols, flavones, anthocyanidins and isoflavones) with ovarian cancer risk, using data from a multicentric case-control study conducted in Italy between 1992 and 1999. The study included 1,031 cases with incident, histologically confirmed epithelial ovarian cancer and 2,411 controls admitted for acute, nonneoplastic conditions to major hospitals in the same catchment areas. In logistic regression models including study center, education, year of interview, parity, oral contraceptive use and family history of ovarian or breast cancer or both, an inverse relation with significant trend in risk was found between ovarian cancer and flavonols [odds ratio (OR), 0.63; 95% confidence intervals (CI) 0.47-0.84] as well as isoflavones (OR, 0.51; 95% CI, 0.37-0.69), comparing the highest versus the lowest quintile. Further adjustment for fruit and vegetable intake did not modify these associations, suggesting that isoflavones and flavonols may have a distinct role in explaining the effect of fruit and vegetable against ovarian cancer. On the basis of our findings and the relevant literature, we infer that isoflavones, and perhaps flavonols, may have favorable effects with respect to ovarian cancer risk.     

Single nucleotide polymorphisms in breast cancer susceptibility gene 1 are associated with susceptibility to lung cancer

BRCA1 is a tumor suppressor that has been found to be involved DNA synthesis during cell replication. In a recent study, the single nucleotide polymorphism (SNP), rs799917, in BRCA1 was found to be associated with the development and progression of various types of tumor. In the present study, the association between rs799917 and susceptibility to lung cancer was evaluated in a Han Chinese population in the Liaoning Province of China. The BRCA1 rs799917 genotypes (C/C, C/T and T/T) were analyzed using TaqMan quantitative PCR in 682 patients with lung cancer and 694 healthy controls, and the results were analyzed using a Student''s t-test, a χ² test and logistic regression analysis. Individuals carrying the C/T or T/T genotype had a lower risk of lung cancer compared with those carrying the C/C genotype [odds ratio (OR), 0.741; P=0.021; and OR, 0.610; P=0.011, respectively). The C/T + T/T genotype group had an even lower risk (OR, 0.709; P=0.005) compared with that in the C/C genotype group. In the stratified analyses of non-smokers, individuals with the C/T or T/T genotype had a lower risk of developing lung cancer compared with that in those carrying the C/C genotype (OR, 0.681; P=0.013; and OR, 0.569; P=0.021, respectively). The stratified analyses of the BRCA1 rs799917 polymorphism based on pathological type, chemotherapy and radiotherapy, showed that in the squamous cell carcinoma, non-chemotherapy and non-radiotherapy subgroups, individuals with the T/T genotype had a lower risk of lung cancer compared with that in those carrying the C/C genotype (OR, 0.454; P=0.007; OR, 0.485; P=0.002; and OR, 0.599; P=0.020, respectively). In conclusion, the T allele of the rs799917 SNP in BRCA1 was associated with a lower risk of lung cancer in the ethnic Han Chinese population in Liaoning Province and may represent a protective factor against lung cancer.     

N‐acetyltransferase polymorphisms are associated with risk of lymphoma subtypes

Genes encoding for arylamine N‐acetyltransferase 1 and 2 (NAT1 and NAT2) have been investigated with alternate findings in relation to risk of non‐Hodgkin lymphoma (NHL). We tested functional haplotype‐based NAT1 and NAT2 gene polymorphisms in relation to risk of lymphoma overall and its major B cell subtypes, diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). We used allele specific primers and multiplex PCR to detect NAT1 and NAT2 haplotypes in 248 patients with incident lymphoma and 208 population controls. We inferred the NAT1 rapid and slow acetylator and the NAT2 rapid, intermediate or slow acetylator phenotype, based on published functional data on the respective genotypes. Odds ratios and 95% confidence intervals (95% CIs) for lymphoma, B‐NHL, DLBCL, FL, CLL, and other B‐NHL combined associated with the inferred rapid NAT1 acetylator and with the intermediate and slow NAT2 acetylator phenotypes were estimated with unconditional and polytomous logistic regression analysis, adjusting for age, gender and education. NAT1 rapid acetylators showed a 2.8‐fold excess risk (95% CI 1.5–5.2) for lymphoma (all subtypes combined). Risk was highest for CLL and FL, with significant heterogeneity detected across subtypes. Risk also increased with decreasing NAT2 acetylating capacity with no heterogeneity detected across B cell lymphoma subtypes. Risks did not vary by gender. Although poor statistical power was a major limitation in our study, larger studies and pooled analyses are warranted to test whether NAT1 and NAT2 gene polymorphisms might modulate risk of specific lymphoma subtypes through the varying metabolic activity of their products. Copyright © 2015 John Wiley & Sons, Ltd.     

Fried potatoes and human cancer

A considerable public concern about cancer risk from acrylamide-rich foods followed the announcement that high concentrations of acrylamide are found in fried potatoes and potato chips and, more generally, in starch-containing foods cooked at high temperatures. From a series of hospital-based case-control studies conducted in Italy and Switzerland between 1991 and 2000, we have analyzed the relation between intake of fried/baked potatoes and cancer risk. The cancer sites considered were oral cavity and pharynx (749 cases, 1772 controls), esophagus (395 cases, 1066 controls), larynx (527 cases, 1297 controls), large bowel (1225 colon and 728 rectum cases, 4154 controls), breast (2569 cases, 2588 controls) and ovary (1031 cases, 2411 controls). All cancer cases were incident and histologically confirmed. Controls were subjects admitted to the same network of hospitals of cases for acute, non-neoplastic conditions. All the odds ratios (OR) for the highest vs. the lowest tertile of intake ranged between 0.8-1.1. We found no evidence of interaction with age, gender, alcohol and tobacco use. Our data provide reassuring evidence for the lack of an important association between consumption of fried/baked potatoes and cancer risk.     

Characteristics associated with early and late melanoma metastases

BACKGROUND:

Differences in risk factors for metastases at different time intervals after treatment have been described in several malignancies; however, to the authors' knowledge, no extensive study examining this issue in melanoma has been conducted to date.

METHODS:

The authors performed a nested case‐control study of patients with melanoma who presented with only local disease. Patients in the case group included 549 patients who developed metastases ≥6 months after surgery. Of these, 320 patients developed metastasis within 3 years after undergoing definitive surgery (early metastases [EM]), and 70 patients developed metastasis ≥8 years after undergoing definitive surgery (late metastases [LM]). For each case, a control patient was chosen who had melanoma but who did not develop metastases in the same interval. Univariate and conditional multivariate logistic regression were used in the analysis of 34 clinical and tumor characteristics.

RESULTS:

Multivariate analysis confirmed previously established risk factors for metastases, such as increasing tumor thickness. In addition, the authors discovered that a personal history of nonmelanoma skin cancer (P = .006) and a history of cancer other than skin cancer (P = .020) also were associated with metastasis. In comparing the 320 EM patients with the 70 LM patients, EM patients were more likely to have thicker lesions (P < .001), ulcerated lesions (P = .016), and a history of nonmelanoma skin cancer (P = .024).

CONCLUSIONS:

In this study, 2 potentially novel risk factors for melanoma metastases were identified, and different profiles of risk factors were constructed for EM versus LM. These differences may be important in future risk identification and stratification for clinical trials and for the management and treatment of patients with melanoma. Cancer 2010. © 2010 American Cancer Society.     

Single nucleotide polymorphisms of follicle-stimulating hormone receptor are associated with ovarian cancer susceptibility

Epidemiological studies suggested that ovulation was associated with ovarian carcinogenesis. Follicle-stimulating hormone (FSH) played an important role in follicular development and was recently found to affect growth of ovarian epithelial cells. Single nucleotide polymorphisms (SNPs) Thr307Ala and Asn680Ser were two non-synonymous variations in the coding region of the FSH receptor (FSHR) gene. This hitherto first case-control study investigating the association between these two FSHR SNPs and the risk of ovarian cancer involved 202 histopathologically confirmed ovarian cancer patients and 266 age-matched cancer-free control subjects using restriction fragment length polymorphism assay and direct sequencing. Our results demonstrated that the 307Ala and 680Ser carriers were associated with significantly increased risk of developing serous and mucinous types of ovarian cancers (P < 0.0005, OR = 2.60, 95% CI = 1.56-4.34; and P < 0.0005, OR = 2.89, 95% CI = 1.73-4.84, adjusted for age, respectively) but not endometrioid and clear cell types. The two SNPs were found to be in modest linkage disequilibrium, D' = 0.804 and 0.701, r2 = 0.581 and 0.406 for the cancer and control groups, respectively. The major haplotype of 307Ala-680Ser was also associated with higher cancer risk (P = 0.033, OR = 1.39, 95% CI = 1.03-1.88), especially for the serous and mucinous carcinomas (P = 0.001, OR = 1.82, 95% CI = 1.27-2.60). Our results suggested that the two FSHR SNPs might affect the susceptibility of women to specific subtypes of ovarian cancer. Different types of ovarian cancer might adopt distinct carcinogenetic pathways. Such understanding may be important in selecting patients for ovulation induction therapy.     

Glucocorticoid therapy and risk of bladder cancer

Background:

Use of immunosuppressive drugs post organ transplantation, and prolonged use of glucorticoids for other conditions have been associated with subsequent risk of certain malignancies, that is, skin cancers and lymphoma. There is evidence that the incidence of bladder cancer is also elevated among organ transplant recipients, however, it is unknown whether other groups of patients, that is, those taking oral glucocorticoids, likewise are at an increased risk.

Methods:

In a population-based case–control study in New Hampshire, USA, we compared the use of glucocorticoids in 786 bladder cancer cases and in 1083 controls. We used unconditional logistic regression analysis to compute adjusted odds ratios (ORs) associated with oral glucocorticoid use.

Results:

In our analysis, the risk of bladder cancer was related to a history of prolonged oral glucocorticoid use (OR=1.85, 95% CI=1.24–2.76, adjusted for age, gender and smoking). Associations with oral glucocorticoid use were stronger for invasive tumours (OR=2.12, 95% CI=1.17–3.85) and tumours with high (3+) p53 staining intensity (OR=2.35, 95% CI=1.26–4.36).

Conclusion:

Our results raise the possibility of an increased risk of bladder cancer from systemic use of glucocorticoids, and a potential role of immune surveillance in bladder cancer aetiology.     

Aspirin and lung cancer in women

The association between aspirin use and lung cancer risk in women was examined in a case-control study nested in the New York University Women's Health Study, a large cohort in New York. Case subjects were all the 81 incident lung cancer cases who had provided information about aspirin use at enrollment and during the 1994-1996 follow up. Ten controls per case were randomly selected from among study participants who matched a case by age, menopausal status, and dates of enrollment and follow-up. Relative to no aspirin use, the odds ratio for lung cancer (all histological sub-types combined) among subjects who reported aspirin use three or more times per week for at least 6 months was 0.66 (95% confidence interval 0.34-1.28), after adjustment for smoking and education. A stronger inverse association was observed in analyses restricted to non-small cell lung cancer (adjusted odds ratio 0.39, 95% confidence interval 0.16-0.96). These results suggest that regular aspirin use might be inversely associated with risk of lung cancer in women, particularly the non-small cell sub-type.     

Soluble Fas level and cancer mortality: findings from a nested case-control study within a large-scale prospective study

Soluble Fas (sFas) is known to play an important role in the development of cancers of various sites. To confirm whether or not the serum sFas level can be a predictor of cancer, we conducted a nested case-control study within a large-scale population-based cohort study in Japan. Serum samples were collected from 39,242 participants (13,839 men and 25,403 women) at baseline, all of whom were followed until 1997 for mortality and until 1994 for cancer incidence. Three controls were randomly selected and matched to each cancer case for gender, age and residential area. Serum values of sFas were measured by enzyme-linked immuno-adsorbent assay, using commercially available kits. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic models, based on 798 total cancer mortality cases and their 2,353 matched controls. The risk of total cancer mortality was increased according to sFas levels, and the OR of the highest quartile compared with that of the lowest was 1.81 (95% CI; 1.40-2.34) after adjusting for smoking and drinking status, and body mass index. This positive association remained unaltered when cases were divided into 2 groups according to the observation period. Our results suggest that serum sFas has a possibility to detect people at high risk for cancer prior to diagnosis, since it increased before cancer diagnosis in those apparently healthy people.     

Macronutrients, fatty acids, cholesterol and renal cell cancer risk

The role of selected macronutrients, fatty acids and cholesterol in the etiology of renal cell carcinoma (RCC) was analyzed using data from a case-control study conducted in 4 Italian areas between 1992 and 2004. Cases were 767 patients with incident, histologically confirmed RCC, admitted to major teaching and general hospitals of the study areas. Controls were 1,534 subjects admitted for acute, nonneoplastic conditions to the same hospitals. Information on dietary habits and nutrient intake was elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (CI) for increasing levels of nutrient intake were estimated after allowance for total energy intake and other potential confounding factors. A direct association with RCC was found for starch intake (OR = 1.9 for highest versus lowest quintile of intake; 95% CI: 1.4-2.6, p-value for trend = 0.001), while an inverse association was found for fats from vegetable sources (OR = 0.6; 95% CI: 0.5-0.8; p-value for trend = 0.002), unsaturated fatty acids (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0002), and polyunsaturated fatty acids (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.001). Among polyunsaturated fatty acids, linoleic acid (OR = 0.5; 95% CI: 0.4-0.7; p-value for trend = 0.0001) and linolenic acid (OR = 0.7; 95% CI: 0.5-1.0; p-value for trend = 0.01) were inversely related to RCC. When 6 major macronutrients were included in the same model, the adverse effect of high intake of starch remained statistically significant, together with the protective effect of polyunsaturated fatty acids. Results were consistent in strata of age, body mass index, treated hypertension, energy intake, stage and family history of RCC.