Male Cancer Risk Research Articles

Overweight, Obesity and Thyroid Cancer Risk: A Meta-analysis of Cohort Studies

This meta-analysis examined the relationship between excess body weight or body mass index (BMI) and risk of thyroid cancer. PubMed(®), MEDLINE(®), EMBASE™ and Academic Search™ Premier databases were searched to identify cohort studies examining the effect of being overweight or obese on the risk of thyroid cancer. The inclusion criteria were met by seven cohort studies (total number of thyroid cancer cases, 5154). The pooled relative risk (RR) of thyroid cancer was 1.13 (95% confidence interval [CI] 1.04, 1.22) for overweight. Obesity was also linked with increased thyroid cancer risk in males and females, the strength of the association increasing with increasing BMI. The combined RR of thyroid cancer was 1.18 (95% CI 1.11, 1.25) for excess body weight (overweight and obesity combined). Being overweight was associated with a significant increase in thyroid cancer risk among non-Asians, but not among Asians. Overweight, obesity and excess body weight were all associated with papillary thyroid carcinoma risk. The association between overweight/obesity/excess body weight and thyroid cancer risk was confirmed.

Role of CYP1A2 polymorphisms on lung cancer risk in a prospective study

Cytochrome P4501A2 (CYP1A2) is a key enzyme for lung carcinogen activation and lung inflammation. We studied the interactions of the CYP1A2 functional variants -3860G/A(rs2069514),-2467T/delT(rs3569413),-163C/A(rs762551)] with occupational/environmental carcinogenic exposures in the development of lung cancer in a case-control study nested in the Danish prospective cohort "Diet, Cancer and Health." At enrollment (1993-1997), blood samples for genotype analyses and information on lifestyle were collected 5 (mean value) years before the onset of the disease. The study population included 425 lung cancer cases and 786 subcohort members, who were gender- and age-matched. We found that -163A carriers were at increased risk of lung cancer (P=0.035) in a multivariate COX regression model, which was adjusted for personal habits (i.e., cumulative smoking, passive smoke at home, alcohol intake, and fruit intake) and occupational exposure. Additionally, the interaction between -2467delT and smoking increases lung cancer risk in males, especially light smokers (<21.5 pack-years, P=0.004). The increased lung cancer risk found in -163C carriers, independent of smoking status, and in -2467delT male smokers, suggests that these variants could influence lung cancer development through different mechanisms (i.e. lung carcinogen activation and lung inflammation).

Vasoactive Peptides with Angiogenesis-Regulating Activity Predict Cancer Risk in Males

Tumor development requires angiogenesis, and antiangiogenesis has been introduced in the treatment of cancer patients; however, how the cardiovascular phenotype correlates with cancer risk remains ill-defined. Here, we hypothesized that vasoactive peptides previously implicated in angiogenesis regulation predict long-term cancer risk. We measured midregional proatrial natriuretic peptide (MR-proANP), proadrenomedullin (MR-proADM), and C-terminal preprovasopressin (copeptin) in fasting plasma from participants of the Malmö Diet and Cancer Study that were free from cancer prior to the baseline exam in 1991 to 1994 (1,768 males and 2,293 females). We used Cox proportional hazards models to determine the time to first cancer event in relation to baseline levels of vasoactive peptides during a median follow-up of 15 years. First cancer events occurred in 366 males and in 368 females. In males, one SD increase of MR-proANP, copeptin, and MR-proADM was independently related to incident cancer [HR (95% CI)] by 0.85 (0.74-0.96), P = 0.012; 1.17 (1.04-1.32), P = 0.009; and 1.12 (0.99-1.26), P = 0.065, respectively, and a summed biomarker score identified an almost 2-fold difference in cancer risk between the top and bottom quartile (P < 0.001). In younger males, the biomarker score identified a more than 3-fold increase in risk between the top and bottom quartile (P < 0.001). Among females, we found no relationship between biomarkers and cancer incidence. Our data suggest that vasoactive peptide biomarkers predict cancer risk in males, particularly in younger males. Our findings may have implications for cancer risk prediction and present novel, potentially drug modifiable, mechanisms underlying cancer development.

Abstract 2783: A novel functional variant is associated with regulation of the prostate stem cell antigen (PSCA) gene and bladder cancer risk in males

Abstract Genome-wide association studies (GWAS) identified allele T of SNP rs2294008 within the prostate stem cell antigen (PSCA) gene as a risk factor for diffuse gastric cancer (OR=1.67, p=2.2×10-15) (The Study Group of Millennium Genome Project for Cancer, Nat Genet, 2008) and bladder cancer (OR=1.13, p=4.4×10-11) (Rothman et al, Nat Genet, 2010). In the present study we used data from the Stage 1 bladder cancer GWAS, which was performed on 8,801 individuals of European ancestry (3,529 cases and 5,115 controls), and information from the 1000 Genomes and HapMap 3 projects to impute all other SNPs within +/- 50kb region surrounding PSCA. Association analysis on the combined set of all genotyped and imputed SNPs (n=375) revealed a novel bladder cancer association signal for a variant genotyped in all samples. The association was found only in males (n=7,359, crude OR =1.14, p=1.15×10-4; adjusted for all covariates and rs2294008, OR=1.13, p=1.32×10-3), while no association was observed in females (n=1,442, crude OR=0.98, p=0.81; adjusted for all covariates and rs2294008, OR=0.98, p=0.82). The low linkage disequilibrium between these two SNPs (D’=0.202 and r2=0.019 in 8801 GWAS samples) suggests these variants are independent. A joint analysis showed that these two SNPs have a compound association with bladder cancer dependent on the number of risk genotypes (0, 1 or 2) in males (adjOR=1.18, p=3.93×10-6) but not in females (adjOR=1.01, p=0.95). The risk allele T of rs2294008 is functional as it introduces a novel translation start site that creates a PSCA protein with a leader peptide extended by 11 amino acids. The novel SNP that was found 10 Kb upstream of rs2294008, lies within an alternative untranslated first exon of PSCA that is marked by a H3K4me3 signal and is in a vicinity of an androgen receptor binding site, suggesting a possible role for this variant in regulation of PSCA promoter activity. In conclusion, a novel independent functional variant associated with bladder cancer risk was found within the PSCA gene, which might be important for male-specific regulation of PSCA expression and carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2783. doi:10.1158/1538-7445.AM2011-2783

Prostate cancer in systemic lupus erythematosus

Our research objective was to estimate prostate cancer risk in systemic lupus erythematosus (SLE), relative to the age-matched general population. A progressive literature review was performed to identify SLE cohort studies with cancer registry linkage for cancer ascertainment. Data were pooled from four studies of large SLE cohorts who met these criteria. The total number of prostate cancers observed was derived by pooling the incident cases across all studies. The total expected number of prostate, derived from applying appropriate general population cancer incidence data to the observed number of patient-years of follow-up for each study, was similarly determined. The parameter of interest was the standardized incidence ratio (SIR), the ratio of observed to expected malignancies. The four studies together provided a pool of 6,068 male SLE patients observed for a total of 38,186 patient-years (mean 6.3 years). Within these subjects, 80 prostate cancers were observed. In each contributing study, the number of cancers expected far exceeded that observed. The pooled SIR estimate for prostate cancer risk in males with SLE, compared to the general population, was 0.72 (95% CI 0.57, 0.89). These data suggest a decreased risk of prostate cancer in SLE; more definite conclusions require additional data. As alterations in androgen pathways can potentially alter prostate risk, a lower risk of prostate cancer in SLE could possibly be due to low hypoadrenergic states which some believe may occur in men with SLE; underlying genetic factors could also be at play. Further study of these issues in large cohorts is needed.

TP53 codon 72 polymorphism is associated with pancreatic cancer risk in males, smokers and drinkers

Tumor protein p53 (TP53) is the best-known tumor suppressor gene and plays a crucial role in carcinogenesis. The TP53 Arg 72 Pro polymorphism has been reported to be a risk factor for several types of cancer, but its association with pancreatic cancer has not been fully evaluated. Therefore, we investigated the effects of this polymorphism on pancreatic cancer in relation to smoking and drinking habits by examining the distribution of the SNP genotypes in 226 pancreatic cancer patients and 448 healthy controls. The frequencies of Arg/Arg, Arg/Pro and Pro/Pro were found to be 37, 49 and 15% in the pancreatic cancer cases and 44, 46 and 10% in the controls, respectively. Compared to the controls with the Arg/Arg genotype, cases with Pro/Pro homozygosity exhibited a significantly increased risk [adjusted odds ratio (OR)=1.70; 95% confidence interval (CI) 1.01-2.88]. In stratified studies, the association was particularly strong in males (OR=2.62; 95% CI 1.32-5.23), particularly in those smoking in excess of 20 pack-years and drinking in excess of 23 g ethanol/day (OR=5.02; 95% CI 1.12-22.51). We found that the TP53 Pro/Pro genotype compared to the Arg/Arg genotype had a profound effect on pancreatic cancer risk among males, particularly among heavy smokers and excessive alcohol drinkers.

Genetic basis of sex-specific resistance to neuro-oncogenesis in (BDIX × BDIV) F2 rats

The identification of cancer susceptibility- and resistance-mediating genes is an essential prerequisite for prevention and early diagnosis of malignant tumors. Model organisms are helpful to identify variant alleles involved in pathways affecting individual cancer risk. BDIX and BDIV rats of both sexes are highly susceptible and resistant, respectively, to the development of N-ethyl-N-nitrosourea (ENU)-induced malignant peripheral nerve sheath tumors (MPNST), predominantly in the trigeminal nerves. Nevertheless, female (BDIV x BDIX) F(2) intercross rats have a lower MPNST incidence and a longer latency time than males. Six of seven autosomal gene loci (Mss1-Mss7) controlling genetic susceptibility and resistance in (BDIV x BDIX) F(2) hybrids exert allele- and sex-specific effects on tumor incidence and/or latency time of variable strength. Homozygous BDIV alleles at Mss4 or Mss7 located on rat chromosomes 6 and 10, respectively, are sufficient to cause almost complete resistance to ENU-induced MPNST development in female F(2) rats regardless of the genotype of the other locus. Both loci display only weak effects on male cancer risk. Survival curves of ENU-treated F(2) females depleted of animals with homozygous BDIV alleles at Mss4 and Mss7 are not significantly different from those of males, suggesting that these loci account mainly for the excess tumor resistance observed in female F(2) rats. By haplotype analysis Mss4 and Mss7 could be narrowed down to 20 and 12 Mb, respectively, providing a basis for the positional identification of candidate genes.

Impact of X Chromosome Genes in Explaining the Excess Risk of Cancer in Males

The authors examined cancer incidence sex ratios in Denmark for 1943-2003 by age group. At nongenital/nonbreast sites, incidences were consistently higher in males. While environmental factors dominate cancer risk, the authors hypothesized that the higher risk in males might be explained by unspecified X chromosome genes' protecting female cells from genotoxic damage. If so, cancer susceptibility would be passed from parent to offspring differently by sex. The authors compared relative risks in offspring of parents with and without cancer histories. For all comparisons, relative risks were similar in offspring of fathers with cancer (relative risk (RR) = 1.14, 95% confidence interval: 1.08, 1.20). Risks in offspring were higher for parents diagnosed before age 50 years and for cancers at the same site rather than different sites. Genital cancer risks were increased in same-sex offspring of parents with genital cancers. Breast cancer risks were high in both daughters (RR = 2.37) and sons (RR = 4.63) of mothers with breast cancer and in daughters (RR = 5.96) of fathers with breast cancer. Thus, X chromosome genetic factors were not responsible for the excess risk of cancer in males. Susceptibility to genital cancer was increased in same-sex offspring, and breast cancer risks were increased in both sons and daughters when either parent had had breast cancer.

Body size and composition and colon cancer risk in women

Studies of colon cancer risk in males have reported strong positive associations with obesity, particularly with central adiposity. The association has been weaker and less consistent for women. In a prospective cohort study of women, body measurements were taken directly; fat mass and fat-free mass being estimated by bioelectrical impedance analysis and central adiposity by waist circumference and waist-to-hip ratio (WHR). Among 24,072 women followed on average for 10.4 years, 212 colon cancers were ascertained via the population cancer registry. We reviewed medical records of all cases and classified them according to anatomic site and stage. The central adiposity measures of WHR (hazard ratio per 0.1 unit increase = 1.31, 95% confidence interval (CI) 1.08-1.58) and waist circumference (hazard ratio per 10 cm increase = 1.14, 95% CI 1.02-1.28) were positively associated with colon cancer risk. There was little or no association between other anthropometric measures and risk of colon cancer. There was some evidence that the associations were stronger for proximal tumors, but no evidence that risk differed by stage for any of the anthropometric measures. Central adiposity appears to be associated with colon cancer risk in women.

Dietary Habits and Stomach Cancer Risk in the JACC Study

BACKGROUND: Despite a declining incidence, stomach cancer is still a dominant cancer in Japan. The association between dietary habits and stomach cancer risk was investigated in a large prospective study in Japan.METHODS: Data were obtained using a self-administered questionnaire from 1988 through 1990. Food frequency questionnaire was used to evaluate the consumption of 33 selected food items. Proportional hazard model was used to determine the hazard ratios (HRs) and their 95% confidence intervals (CIs) of stomach cancer for different levels of the dietary intakes.RESULTS: A western style breakfast showed an inverse association with stomach cancer risk in males (HR=0.49, 95% CI: 0.35-0.70). Women who consumed liver three to four times per week and more than once per day had a significant increased risk, respectively (HR=2.02, 95% CI: 1.12-3.63, HR=3.16, 95% CI: 1.16-8.62 ). A clear dose-response relationship between the intake of liver and stomach cancer risk was observed. We found no association between stomach cancer mortality and the consumption of fruit such as mandarin orange, and vegetables such as carrots and spinach in both men and women. The consumption of high salt foods such as miso soup and pickles was also not significantly associated with the mortality of stomach cancer in both sexes.CONCLUSION: This prospective study suggested that a western-style breakfast is associated with a lower risk of stomach cancer, although some differences in the association were seen between men and women.

Mortality in Florida professional firefighters, 1972 to 1999

Exposure to occupational hazards among firefighters may lead to increased mortality from cancer, lung, or heart disease. Age- and gender-adjusted mortality rates of 34,796 male and 2,017 female Florida professional firefighters between 1972 and 1999 were compared with the Florida general population. One thousand four hundred eleven male and 38 female firefighter deaths with known causes were identified. In male firefighters, mortality due to all causes and most non-malignant diseases was significantly less than expected. There was no excess overall mortality from cancer, but excesses existed for male breast cancer [standardized mortality ratio (SMR = 7.41; 95% confidence interval (CI): 1.99-18.96) and thyroid cancer (SMR = 4.82; 95% CI: 1.30-12.34)]. Mortality from bladder cancer was increased and approached statistical significance (SMR = 1.79; 95% CI: 0.98-3.00). Firefighters certified between 1972 and 1976 had excess mortality from bladder cancer (SMR = 1.95; 95% CI: 1.04-3.33). Female firefighters had similar morality patterns to Florida women except for atherosclerotic heart disease (SMR = 3.85; 95% CI: 1.66-7.58). Excess mortality risk from bladder cancer may be related to occupational exposure during firefighting. The thyroid cancer and breast cancer risk in males, as well as the excess risk of cardiovascular disease mortality noted in females warrant further investigation.

Outdoor air pollution and lung cancer: recent epidemiologic evidence.

Outdoor air pollution and lung cancer: recent epidemiologic evidence.

CYP17 promoter polymorphism and breast cancer risk in males and females in relation to BRCA2 status.

A T–C polymorphism in the promoter region of the CYP17 gene has been associated with male and female breast cancer risk as well as early-onset familial breast cancer. The potential role of this polymorphism was investigated in relation to breast cancer risk in Icelandic male and female carriers and noncarriers of a BRCA2 mutation. The study population consisted of 39 male and 523 female breast cancer cases and 309 male and 395 female controls. Of the cases, 15 males and 55 females carried a BRCA2 mutation. We did not find a significant association between male breast cancer risk and CYP17 genotypes. Among male breast cancer cases, the frequency of the CC genotype was higher among carriers of the 999del5 mutation (33.3%) than noncarriers (16.7%), although this difference also did not reach a statistical significance. No association was observed with breast cancer risk among females irrespective of menopausal status, stage of the disease or BRCA2 status. Our findings do not indicate a role for the CYP17 T–C polymorphism in female breast cancer, but a role in male carriers of a BRCA2 mutation could not be excluded because of the small sample size.

Variation in Cancer Risks, by Mutation Position, in BRCA2 Mutation Carriers

Cancer occurrence in 164 families with breast/ovarian cancer and germline BRCA2 mutations was studied to evaluate the evidence for genotype-phenotype correlations. Mutations in a central portion of the gene (the "ovarian cancer cluster region" [OCCR]) were associated with a significantly higher ratio of cases of ovarian:breast cancer in female carriers than were mutations 5' or 3' of this region (P<.0001), extending previous observations. The optimal definition of the OCCR, as judged on the basis of deviance statistics, was bounded by nucleotides 3059-4075 and 6503-6629. The relative and absolute risks of breast and ovarian cancer associated with OCCR and non-OCCR mutations were estimated by a conditional likelihood approach, conditioning on the set of mutations observed in the families. OCCR mutations were associated both with a highly significantly lower risk of breast cancer (relative risk [RR] 0.63; 95% confidence interval (95% CI) 0.46-0.84; P=.0012) and with a significantly higher risk of ovarian cancer (RR = 1.88; 95% CI = 1.08-3.33; P=.026). No other differences in breast or ovarian cancer risk, by mutation position, were apparent. There was some evidence for a lower risk of prostate cancer in carriers of an OCCR mutation (RR = 0.52; 95% CI = 0.24-1.00; P=.05), but there was no evidence of a difference in breast cancer risk in males. By age 80 years, the cumulative risk of breast cancer in male carriers of a BRCA2 mutation was estimated as 6.92% (95% CI = 1.20%-38.57%). Possible mechanisms for the variation in cancer risk are suggested by the coincidence of the OCCR with the RAD51-binding domain.

Risk of Testicular Cancer in Cohort of Boys With Cryptorchidism

Abstract Objective: To determine the risk of testicular cancer in relation to undescended testis and its treatment based on recorded details of the maldescent, treatment, and biopsy from case notes. Design: Cohort study. Setting: Hospital for Sick Children, Great Ormond Street, London. Subjects: 1075 boys with cryptorchidism treated by orchidopexy or hormones at the hospital during 1951-64. Main outcome measures: Relative risk of testicular cancer in the cohort compared with men in the general population. Results: 12 testicular cancers occurred in 11 of the patients during follow up to mid-1990 (relative risk of cancer in males with cryptorchidism=7.5 (95% confidence interval 3.9 to 12.8)). The relative risk fell significantly beyond 15 years after orchidopexy but did not decrease with younger age at orchidopexy. Risk was significantly raised in testes that had had biopsy samples removed during orchidopexy (relative risk=66.7 (23.9 to 143.3) compared with a testis in a man in the general population) and was significantly greater in these testes than in undescended testes that had not had biopsy samples taken at orchidopexy (6.7 (2.7 to 13.5)). No reasons for biopsy or distinguishing clinical aspects of the testes that had had biopsy samples taken and later developed malignancies were evident in the case notes. No histological abnormalities were evident at initial biopsy except in one testis that had features of dysgenesis. Conclusions: Biopsy seems to be a stronger risk factor for testicular cancer than any factor previously identified. The trauma of open biopsy may contribute substantially to risk of malignancy or the testes may have been selected for biopsy on the basis of clinical factors predictive of malignancy but not mentioned in the case notes. Key messages The reasons for increased risk of testicular cancer in cryptorchidism are unclear Risk of testicular cancer was determined in follow up of 1075 boys with cryptorchidism treated during 1951-64 The relative risk of testicular cancer in the cohort compared with men in the general population was 7.5 and did not decrease with younger age at orchidopexy Risk was much greater in undescended testes from which a biopsy sample had been taken during orchidopexy than in those with no biopsy Biopsy was a stronger risk factor for testicular cancer than any factor previously identified

Risk of testicular cancer in cohort of boys with cryptorchidism

Objective: To determine the risk of testicular cancer in relation to undescended testis and its treatment based on recorded details of the maldescent, treatment, and biopsy from case notes.Design: Cohort...

Occupation-related risks for colorectal cancer.

Several population data bases were used to generate hypotheses about associations between colorectal cancer and workplace exposures. The Third National Cancer Survey interview sample was used to select 343 male and 208 female cases and 626 male and 1,235 female cancer controls. Potential work exposures were assigned with the use of data from the National Institute for Occupational Safety and Health National Occupational Hazard Survey. Dietary factors were modeled from the National Health and Nutrition Examination Survey data. Work-related stress was considered with the use of a model based on the U.S. Department of Labor's Quality of Employment Survey. Other risk factors included age, race, ponderosity, and menopausal status. Logistic analysis yielded hypotheses for colon cancer risk in males with potentially high exposure to solvents, abrasives, and fuel oil and in those in jobs with high demand and low control (high "stress"). Hypotheses emerged for females with potentially high exposure to dyes, solvents, and grinding wheel dust.

Dietary vitamin A, carotene, vitamin C and risk of lung cancer in Hawaii.

The authors conducted a case-control study among the multiethnic population of Hawaii to test the hypotheses that lung cancer risk is inversely associated with dietary intake of total vitamin A, carotene, and vitamin C. Detailed dietary interviews were completed between September 1979 and October 1982 for 364 primary lung cancer patients and 627 general population controls matched on age and sex. After adjusting for a number of potentially confounding variables, including ethnicity, smoking history, and occupation, evidence was found that total vitamin A intake (food sources plus supplements), vitamin A intake from food sources only, and carotene intake were each inversely associated with lung cancer risk in males, but not in females. Among males, a monotonic dose-response relationship was found only for total vitamin A intake. However, a comparison of the lowest and highest quartiles of intake gave similar results for each of the three measures of nutrient intake: total vitamin A (odds ratio (OR) = 1.8; 95% confidence limits (CL) = 1.1-3.1), vitamin A from foods (OR = 2.0; 95% CL = 1.2-3.5), and carotene (OR = 2.2; 95% CL = 1.3-3.7). Similar analyses revealed no significant association between dietary vitamin C intake and lung cancer risk.