Background
Aldehyde dehydrogenase 2 (
ALDH2
; rs671, Glu504Lys) and alcohol dehydrogenase 1B (
ADH1B
; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde ...accumulation after alcohol drinking. To date, however, evidence for a significant
ALDH2
–alcohol drinking interaction and a mediation effect of
ALDH2
/
ADH1B
through alcohol drinking on gastric cancer have remained unclear. We conducted two case–control studies to validate the interaction and to estimate the mediation effect on gastric cancer.
Methods
We calculated odds ratios (OR) and 95% confidence intervals (CI) for
ALDH2
/
ADH1B
genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways.
Results
ALDH2
Lys alleles had a higher risk with increased alcohol consumption compared with
ALDH2
Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04–6.27;
P
for trend = 0.007), indicating a significant
ALDH2
–alcohol drinking interaction (
P
interaction
= 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38–2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76–0.92) of the
ALDH2
Lys alleles with the
ALDH2
–alcohol drinking interaction. No significant association of
ADH1B
with gastric cancer was observed.
Conclusion
The observed
ALDH2
–alcohol drinking interaction and the direct effect of
ALDH2
Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.
Full text
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The impact of alcohol on the risk of stomach cancer is controversial. Although aldehyde dehydrogenase 2 (ALDH2) Glu504Lys (rs671) polymorphism has a strong effect on acetaldehyde metabolism, little ...is known about its impact on stomach cancer risk when combined with alcohol drinking. This case-control study included a total of 697 incident stomach cancer case subjects and 1372 non-cancer control subjects who visited Aichi Cancer Center between 2001 and 2005. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ALDH2 genotypes and alcohol consumption using logistic regression models after adjustment for potential confounders, including Helicobacter pylori infection. The ALDH2 504Lys allele was associated with the risk of stomach cancer, with adjusted ORs of 1.40 (95% CI, 1.11-1.76) for Glu/Lys and 1.73 (1.12-2.68) for Lys/Lys compared with Glu/Glu. Heavy drinking was associated with risk (OR 1.72, 1.17-2.52) after adjustment for ALDH2 genotype and other confounders. Moreover, ORs for heavy drinking were 1.28 (0.77-2.12) for those with ALDH2 Glu/Glu and 3.93 (1.99-5.79) for those with the ALDH2 Lys allele relative to non-drinkers with the Glu/Glu genotype (P for interaction = 0.0054). In conclusion, ALDH2 and alcohol drinking showed interaction for risk factors of stomach cancer, indicating that acetaldehyde plays a role in stomach carcinogenesis.
An 87-year-old woman was diagnosed with rectal cancer and underwent robot-assisted Hartmann surgery. On postoperative day (POD) 6, back pain appeared, and CT showed an infected aortic aneurysm and ...multiple liver abscesses. Klebsiella pneumoniae was detected in blood culture and the patient was treated with antibiotics. On POD 14, CT showed an enlarged aortic aneurysm, and the patient was diagnosed with an urgent rupture and underwent an emergency stent graft insertion. The patient’s progress was good and she was discharged ambulatory on POD 46. Klebsiella pneumoniae is an attenuated resident bacterium in the gastrointestinal tract. Patient factors, surgical invasion, and other factors, in addition to bacteremia caused by intestinal mobilization and manipulation at the time of resection and stoma placement, may have led to sepsis, resulting in infection of the aortic wall and multiple liver abscesses. We describe this case as the first report of infected aortic aneurysms and multiple liver abscesses in the early postoperative period after surgery for colorectal cancer.
A 67-year-old man presented complaining of an upset stomach. On upper gastrointestinal endoscopy, an irregular elevated lesion was seen near the gastric cardia, which was diagnosed by biopsy as ...poorly differentiated adenocarcinoma. Total gastrectomy and D2 lymph node dissection were performed. Histopathological investigation resulted in a diagnosis of pStage IIb large-cell gastric neuroendocrine carcinoma. Combination carboplatin and irinotecan therapy was given as postoperative adjuvant chemotherapy. Two years postoperatively, a solitary brain metastasis was identified and treated by stereotactic radiotherapy with a CyberKnife. Treatment for this brain metastasis was subsequently performed repeatedly. Around 3 years 10 months postoperatively, the patient also developed normal-pressure hydrocephalus, and a lumboperitoneal shunt procedure was performed. He died of the original cancer at 4 years 2 months postoperatively. No lymph node or other distant metastasis was observed during the clinical course. This extremely rare case of solitary brain metastasis of large-cell gastric neuroendocrine carcinoma is reported along with a short discussion of the literature.
A 64-year-old woman presented with abdominal pain and vomiting. CT and colonoscopy revealed a tumorous stricture in the upper rectum. From pathological findings of a biopsied specimen, we diagnosed ...the case as adenocarcinoma probably arisen from the gynecological organ rather than from the intestine. She had undergone total hysterectomy and right oophorectomy for endometriosis at the age of 39. We performed laparoscopic low anterior resection of rectum, D3 lymph node dissection, and associated left oophorectomy. The intraoperative frozen section diagnosis was endometroid adenocarcinoma of the rectum. A nodule on the hepatic surface which was detected and resected during the surgery was diagnosed as metastasis of adenocarcinoma. A lot of lymph nodes were metastasis positive. After the surgery, six courses of adjuvant chemotherapy with paclitaxel, carboplatin, and bevacizumab were conducted. She developed lymph node and liver metastases one year and 3 months after the operation, so that chemotherapy was resumed. As malignant transformation from rectal endometriosis is rare, we present this case together with some bibliographical comments.
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