Mutations in Fanconi anemia genes and the risk of esophageal cancer.

The incidence of esophageal squamous cell carcinoma (ESCC) is very high in northeastern Iran. Previously, we reported a strong familial component of ESCC among Turkmens, who constitute approximately one-half of the population of this region. We hypothesized that the genes which cause Fanconi anemia might be candidate genes for ESCC. We sequenced the entire coding regions of 12 Fanconi anemia genes in the germline DNA of 190 Turkmen cases of ESCC. We identified three heterozygous insertion/deletion mutations: one in FANCD2 (p.Val1233del), one in FANCE (p.Val311SerfsX2), and one in FANCL (p.Thr367AsnfsX13). All three patients had a strong family history of ESCC. In addition, four patients (out of 746 tested) were homozygous for the FANCA p.Ser858Arg mutation, compared to none of 1,373 matched controls (OR = 16.7, 95% CI = 6.2-44.2, P = 0.01). The p. Lys3326X mutation in BRCA2 (also known as Fanconi anemia gene FANCD1) was present in 27 of 746 ESCC cases and in 16 of 1,373 controls (OR = 3.38, 95% CI = 1.97-6.91, P = 0.0002). In summary, both heterozygous and homozygous mutations in several Fanconi anemia-predisposing genes are associated with an increased risk of ESCC in Iran.

Correlation between Cigarette Smoking and Urine Cotinine Level in Gastric Cancer Patients.

Various substances in cigarette smoke including nicotine have been shown to promote/induce cancer cell proliferation. Since cotinine has a longer half life and stability in the blood, it has become the preferred biomarker for cigarette smoking exposure. Seventy-three gastric cancer patients were included in this study. The tumor tissues were stained with H & E for pathological evaluation. The cotinine levels were measured in urine using a competitive ELISA. Tumors were 90% adenocarcinoma with 63% intestinal and 37% diffuse subtypes. Tumors were poorly (45.2%) or moderately differentiated (41.1%) and localized mainly (77%) in the upper part of stomach. The levels of cotinine were significantly different between smoker (283.83 ± 178.10 ng/mL) and non-smoker (39.28 ± 113.34 ng/mL) groups (p < 0.001). However, there is no-significant correlation between tumor characteristics and cotinine level in smoker patients. Cotinine level correlates with smoking in gastric patients, however, correlation with the tumor features has not been observed.

Are the serum biomarkers pepsinogen I and II good predictors for the detection of subjects with atrophic gastritis in areas that have different gastric cancer incidence?

BACKGROUND: Northern Iran (Ardabil) is characterized by a high gastric cancer (GC) rate, whereas Southern Iran (Kerman and Yazd) has a low GC rate. The aim of this study is to verify the potential for pepsinogen I and II to detect atrophic gastritis (AG) in both high and low risk populations for GC. METHODS: Sera of blood donors and patients with GC from Ardebil, Kerman and Yazd were used to measure levels of pepsinogen I, II and H. pylori IgG antibody. GC rates in these cities were determined according to the Cancer Registry and upper gastrointestinal (GI) endoscopy results.  RESULTS: There were 449 subjects with an average age of 45 ± 15 years. The GC rate in the endoscopy units of the hospital in Ardabil was four times higher than Kerman or Yazd. The mean serum pepsinogen I levels did not differ between Ardabil (102 ± 42.6 µg/mL), Kerman (103.3 ± 49.8 µg/mL), and Yazd (111.7 ± 39 µg/mL). Pepsinogen II levels were: 8.1 ± 4.7 µg/mL (Ardabil), 7.5 ± 5.3 µg/mL (Kerman), and 7.6 ± 4.4 µg/mL (Yazd), which were not different. The H. pylori infection rates were: Ardabil (61%), Kerman (55%), and Yazd (73%). A low ratio of pepsinogen I to II (≤3) was seen in Ardabil (1.3%), Kerman (1.9%), and Yazd (0.0%), which was not significant. A total of 51.9% of GC patients from Ardabil had normal pepsinogen I (≥70 µg/mL) levels and pepsinogen I/II ratios that were >5.  CONCLUSION: Serum biomarkers pepsinogen I and II and their ratios are probably not sensitive predictors of AG in areas that have either a high or low GC prevalence. This finding is likely related to the lack of an association between GC and advanced AG.