Sara Raimondi

Smoking and colorectal cancer: a meta-analysis.

CONTEXT Colorectal cancer is the third most common form of cancer and the fourth most frequent cause of cancer deaths worldwide. The association between cigarette smoking and colorectal cancer has been inconsistent among studies. OBJECTIVE To clarify the association of cigarette smoking and colorectal cancer, we performed a comprehensive literature search and a meta-analysis of observational studies considering both incidence and mortality. DATA SOURCES We performed a literature search using PubMed, ISI Web of Science (Science Citation Index Expanded), and EMBASE to May 2008, with no restrictions. We also reviewed references from all retrieved articles. STUDY SELECTION All articles that were independent and contained the minimum information necessary to estimate the colorectal cancer risk associated with cigarette smoking and a corresponding measure of uncertainty. DATA EXTRACTION Articles were reviewed and data were extracted and cross-checked independently by 3 investigators, and any disagreement was resolved by consensus among all 3. RESULTS One hundred six observational studies were included in the analysis of incidence. Twenty-six studies provided adjusted risk estimates for ever smokers vs never smokers, leading to a pooled relative risk of 1.18 (95% confidence interval [CI], 1.11-1.25). Smoking was associated with an absolute risk increase of 10.8 cases per 100,000 person-years (95% CI, 7.9-13.6). We found a statistically significant dose-relationship with an increasing number of pack-years and cigarettes per day. However, the association was statistically significant only after 30 years of smoking. Seventeen cohort studies were included in the analysis of mortality. The pooled risk estimate for ever vs never smokers was 1.25 (95% CI, 1.14-1.37). Smoking was associated with an absolute risk increase of 6.0 deaths per 100,000 person-years (95% CI, 4.2-7.6). For both incidence and mortality, the association was stronger for cancer of the rectum than of the colon. CONCLUSION Cigarette smoking is significantly associated with colorectal cancer incidence and mortality.

Epidemiology of pancreatic cancer: an overview

Pancreatic cancer, although infrequent, has an exceptionally high mortality rate, making it one of the four or five most common causes of cancer mortality in developed countries. The incidence of pancreatic cancer varies greatly across regions, which suggests roles for lifestyle factors, such as diet, or environmental factors, such as vitamin D exposure. Smoking is the most common known risk factor, and is the cause of 20–25% of all pancreatic tumors. Alcohol does not seem to be a risk factor, unless it leads to chronic pancreatitis, which is a probable risk factor. Long-standing diabetes increases the risk of pancreatic cancer, but can also be an early manifestation of pancreatic tumors. 5–10% of patients with pancreatic cancer have an underlying germline disorder, while the remaining percentage of cancer cases is thought to be caused by somatic mutations. Some individual studies suggest that mutations in various polymorphic genes can lead to small increases in the risk of pancreatic cancer, but these findings need to be replicated. Rising prevalence of smoking in developing countries, improved diagnosis and increasing population longevity are all likely to increase the global burden of pancreatic cancer in the coming decades.

Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection ☆

Acute pancreatitis, chronic pancreatitis and pancreatic cancer are responsible for most of the burden of exocrine pancreatic disease. Glandular damage from recurrent bouts of acute pancreatitis can lead to irreversible changes characteristic of chronic pancreatitis. In recent decades accumulating evidence has defined longstanding pre-existing chronic pancreatitis as a strong risk factor for pancreatic cancer. The lag period between diagnosis of chronic pancreatitis and pancreatic cancer is usually one or two decades: pancreatitis appearing a year or two before the diagnosis of pancreatic cancer is often the result of tumour-related ductal obstruction. The risk of developing pancreatic cancer appears to be highest in rare types of pancreatitis with an early onset, such as hereditary pancreatitis and tropical pancreatitis. Even though there is a strong link between chronic pancreatitis and pancreatic cancer, over a 20 year period only around five percent of patients with chronic pancreatitis will develop pancreatic cancer. Until the development of more sophisticated screening procedures, screening is not recommended for patients with chronic pancreatitis.

MC1R variants, melanoma and red hair color phenotype: a meta-analysis.

Melanocortin‐1‐receptor (MC1R) is one of the major genes that determine skin pigmentation. MC1R variants were suggested to be associated with red hair, fair skin, and an increased risk of melanoma. We performed a meta‐analysis on the association between the 9 most studied MC1R variants (p.V60L, p.D84E, p.V92M, p.R142H, p.R151C, p.I155T, p.R160W, p.R163Q and p.D294H) and melanoma and/or red hair, fair skin phenotype. Eleven studies on MC1R and melanoma, and 9 on MC1R and phenotype were included in the analysis. The 7 variants p.D84E, p.R142H, p.R151C, p.I155T, p.R160W, p. R163Q and p.D294H were significantly associated with melanoma development, with ORs (95%CI) ranging from 1.42 (1.09–1.85) for p.R163Q to 2.45 (1.32–4.55) for p.I155T. The MC1R variants p.R160W and p.D294H were associated both with red hair and fair skin, while p.D84E, p.R142H, and p.R151C were strongly associated with red hair only‐ ORs (95%CI) ranged from 2.99 (1.51–5.91) for p.D84E to 8.10 (5.82–11.28) for p.R151C. No association with melanoma or phenotype was found for p.V60L and p.V92M variants. In conclusion this meta‐analysis provided evidence that some MC1R variants are associated both with melanoma and phenotype, while other are only associated with melanoma development. These results suggest that MC1R variants could play a role in melanoma development both via pigmentary and non‐pigmentary pathways.

Cigarette Smoking and Adenomatous Polyps: A Meta-analysis

BACKGROUND & AIMS Through the past 2 decades, a consistent association between cigarette smoking and colorectal adenomatous polyps, recognized precursor lesions of colorectal cancer, has been shown. We performed a meta-analysis to provide a quantitative pooled risk estimate of the association, focusing on the different characteristics of the study populations, study designs, and clinical feature of the polyps. METHODS We performed a comprehensive literature search of studies linking cigarette smoking and adenomas. We used random effects models to evaluate pooled relative risks and performed dose-response, heterogeneity, publication bias, and sensitivity analyses. RESULTS Forty-two independent observational studies were included in the analysis. The pooled risk estimates for current, former, and ever smokers in comparison with never smokers were 2.14 (95% confidence interval [CI], 1.86-2.46), 1.47 (95% CI, 1.29-1.67), and 1.82 (95% CI, 1.65-2.00), respectively. The association was stronger for high-risk adenomas than for low-risk adenomas. Studies in which all controls underwent full colonoscopy showed a higher risk compared with studies in which some or all controls underwent partial colon examination. CONCLUSIONS This meta-analysis provides strong evidence of the detrimental effect of cigarette smoking on the development of adenomatous polyps. Smoking is important for both formation and aggressiveness of adenomas.

Review and meta-analysis on vitamin D receptor polymorphisms and cancer risk

It was suggested that vitamin D levels influence cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D. Results from previous studies on the association of VDR polymorphisms with different cancer types are somewhat contradictory, and the role of VDR in the etiology of cancer is still equivocal. We therefore performed a meta-analysis on the association between the two most studied VDR polymorphisms (FokI and BsmI) and any cancer site. Up to January 2009, we identified 67 independent studies. We used random-effects models to provide summary odds ratio (SOR) for VDR polymorphisms and cancer. We tested homogeneity of effects across studies and publication bias and explored between-study heterogeneity. When comparing FokI ff with FF carriers, we found a significant increase in skin cancer [SOR; 95% confidence intervals (CIs): 1.30; 1.04-1.61] and breast cancer (SOR; 95%CI: 1.14; 1.03-1.27) risk. For the same genotype comparison, we found a significantly higher risk of cancer when we pooled estimates from cancer sites possibly associated with vitamin D levels (prostate, breast, skin, ovary, non-Hodgkin lymphoma and colorectal). A significant reduction in prostate cancer risk was observed for carriers of BsmI Bb compared with bb genotype (SOR; 95%CI: 0.83; 0.69-0.99). In Caucasian populations, both Bb and BB carriers had a significant reduced risk of cancer at any site. In conclusion, this meta-analysis showed that VDR FokI and BsmI polymorphisms might modulate the risk of cancer of breast, skin and prostate and possibly affect cancer risk at any site in Caucasians.

Hepatitis C virus genotype 1b as a risk factor for hepatocellular carcinoma development: a meta-analysis.

BACKGROUND/AIMS Hepatitis C virus (HCV) is a known risk factor for hepatocellular carcinoma (HCC), but whether the risk varies among patients infected with different HCV genotypes is still controversial. We performed a meta-analysis to clarify whether the genotype 1b is associated with a higher risk of HCC than other genotypes. METHODS We identified 57 relevant papers through a literature search to December 2007 but, since age could represent a major confounder, we focused the meta-analysis on the 21 studies presenting age-adjusted risk estimates for HCV genotype 1b vs. other genotypes. We used random-effects models with the DerSimonian-Laird method and assessed heterogeneity between studies and publication bias. RESULTS Patients infected with HCV genotype 1b have almost double the risk to develop HCC than those infected with other genotypes (Relative Risk (95% Confidence Intervals) = 1.78(1.36-2.32)). The pooled risk estimate was somewhat lower when we restricted the analysis to the eight studies conducted in patients with liver cirrhosis (1.60;1.07-2.39) or considering the 36 studies presenting only crude data (1.63;1.30-2.06). In seven studies excluding patients with liver cirrhosis, the RR (95% CI) increased to 2.46(1.69-3.59). CONCLUSIONS This meta-analysis suggests that HCV genotype 1b plays an important role in HCC development, especially in patients with early stage liver disease.

Vitamin D and skin cancer: A meta-analysis

A comprehensive bibliographic search of the literature was conducted to identify studies on Cutaneous Malignant Melanoma (CMM) and non-melanoma skin cancer (NMSC), Vitamin D receptor (VDR) polymorphisms, Vitamin D intake and 25(OH)D serum levels. Fully adjusted risk estimates were found and extracted for the two polymorphisms FokI and BsmI and Vitamin D intake. Ten studies were included in the meta-analysis, with a total of 6805 skin cancer cases. We found an association with CMM for both polymorphisms. The summary relative risks (SRR) for the studies on CMM were: 1.21 (1.03-1.42) and 1.21 (0.95-1.54) for the Ff and ff versus wild-type of FokI, respectively. The SRR for ff versus wild-type became significant with the inclusion of NMSC. The SRR for the studies on CMM were: 0.78 (0.65-0.92) and 0.75 (0.59-0.95) for the Bb and BB versus wild-type of BsmI, respectively. There is also a slight indication of a role of dietary Vitamin D in CMM development. In conclusion, this meta-analysis suggests a possible significant role of VDR FokI and BsmI polymorphism in CMM and NMSC risk. The association with Vitamin D intake is less clear and further studies could be useful to clarify the role of diet.

Early Onset Pancreatic Cancer: Evidence of a Major Role for Smoking and Genetic Factors

Pancreatic cancer ranks 4th as a cause of cancer mortality and in ∼5% to 10% of patients, this lethal tumor develops before age 50. We used age-, sex-, and country-specific cancer incidence and mortality data to describe the burden of early onset pancreatic cancer (EOPC) worldwide. We also reviewed the current published evidence on smoking and genetic factors associated with EOPC. We found an excess of EOPC resulting in a substantial number of years-of-life-lost in countries from Central and Eastern Europe. Worldwide, the proportion of EOPC is strongly correlated with lung cancer mortality (R2 = 0.53), suggesting that approximately half of the variation in the proportion of EOPC could be explained by smoking. The unusual pattern of the incidence of pancreatic cancer by gender and race supports the primary role of smoking in the etiology of EOPC: the excess male-to-female rate ratio, attributable mainly to smoking, gradually approaches unity with increasing age. Moreover, male-to-female rate ratios are greater in blacks than in whites only in younger patients. Published studies also identified genetic alterations involved either alone or in association with smoking in the development of EOPC. In conclusion, EOPC constitutes only 1% to 5% of the total deaths from pancreatic cancer worldwide, but is responsible for 20% to 30% of the total number of years-of-life-lost caused by the disease. Smoking and genetic mutations are the major identified risk factors and seem to be even more important for EOPC than for PC in older age groups. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1894–7)

Meta-analysis of risk factors for cutaneous melanoma according to anatomical site and clinico-pathological variant

A systematic meta-analysis was performed to evaluate if cutaneous melanoma (CM) risk factors differ depending on body site and histological type. Adjusted estimates were extracted from 24 observational studies, for a total of 16,180 cases. Multivariate random-effects models were used to obtain summary relative risk (RR) estimates for all risk factors by body site and histological type. Summary RRs suggest that high naevus counts are strongly associated with CM on usually not sun exposed sites (p<0.001) while different patterns of sun exposure show a tendency for higher RRs for CM on usually sun exposed sites than on other body sites (p=0.087). Continuous pattern was found to be significantly inversely associated with CM for unexposed sites (p=0.01). RRs also differed by body site for skin (p=0.01) and hair colour (p=0.01), and these differences could be attributed to gene variability. This finding seems to suggest different aetiologic pathways of melanoma development by anatomical site.