Gallstones, cholecystectomy and risk of cancers of the liver, biliary tract and pancreas

Chow, WH; Johansen, Christoffer; Gridley, Gloria; Mellemkjær, Lene; Olsen, Jørgen H.; Fraumeni, Jr Jf

doi:10.1038/sj.bjc.6690101

Cited by 133 publications

(119 citation statements)

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“…Results from case-control studies have been conflicting (Haines et al, 1982;Shibata et al, 1994;Ekbom et al, 1996;Coughlin et al, 2000), although some indicate a 30 -70% increased risk of pancreatic cancer in association with gallstones or after a cholecystectomy (Chow et al, 1999;Gullo, 1999;Silverman et al, 1999;Silverman, 2001). In the largest case-control study, Silverman (2001) observed a RR of 1.7 (95%CI, 1.0 -1.3).…”

Section: Discussionmentioning

confidence: 99%

“…The presence of gallstones, on the other hand, appears to be associated with chronic pancreatitis (Hardt et al, 2001), but whether chronic pancreatitis predisposes to pancreas cancer remains controversial (Lowenfels et al, 1993;Ekbom et al, 1994). Some of the earlier studies reported relative risks of pancreatic cancer of 1.2 -2.0 among individuals who had undergone a cholecystectomy previously (Haines et al, 1982;Shibata et al, 1994;Ekbom et al, 1996;Chow et al, 1999;Gullo, 1999;Silverman et al, 1999;Coughlin et al, 2000); however, the strength of the association remains uncertain because of the retrospective design of most analyses and the reliance on nextof-kin respondents. Prospective studies can overcome these limitations.…”

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Gallstones, cholecystectomy, and the risk for developing pancreatic cancer

et al. 2002

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We examined the relation between gallstones, cholecystectomy, and the development of pancreatic cancer in the Nurses' Health Study and the Health Professionals Follow-up Study. Among 104 856 women and 48 928 men without cancer at baseline, we documented 349 cases of pancreatic cancer during up to 16 years of follow-up. Participants were classified according to a history of gallstones or cholecystectomy. The age-adjusted relative risk of pancreatic cancer following cholecystectomy or diagnosis of gallstones was 1.31 (95% CI, 0.93 -1.83). However, adjustment for other pancreatic cancer risk factors attenuated the association (RR=1.11, 95% CI, 0.78 -1.56); this risk did not increase with increasing time following cholecystectomy or gallstones. Gallstones or cholecystectomy do not appear to be significant risk factors for pancreatic cancer. Pancreatic cancer is the fifth leading cause of cancer-related mortality in the US (Greenlee et al, 2001). New environmental risk factors have consistently been linked to the risk of pancreatic cancer. Animal models suggest an important role for cytokines in experimental pancreatic carcinogenesis (Watanapa and Williamson, 1993). Cholecystokinin (CCK) has been shown to stimulate both gallbladder contraction and pancreatic enzyme secretion (Marx et al, 1987;Smith et al, 1990) and to have a trophic effect on pancreatic acinar cells (Rivard et al, 1991). The presumed increased release of CCK following cholecystectomy (Hyvarinen and Partanen, 1987) might contribute to an increased risk for pancreatic cancer risk following gallbladder removal. In addition, cholecystectomy may suppress the normal inhibitory effect of CCK on the Sphincter of Oddi (Luman et al, 1997). The presence of gallstones, on the other hand, appears to be associated with chronic pancreatitis (Hardt et al, 2001), but whether chronic pancreatitis predisposes to pancreas cancer remains controversial (Lowenfels et al, 1993;Ekbom et al, 1994). Some of the earlier studies reported relative risks of pancreatic cancer of 1.2 -2.0 among individuals who had undergone a cholecystectomy previously (Haines et al, 1982;Shibata et al, 1994;Ekbom et al, 1996;Chow et al, 1999;Gullo, 1999;Silverman et al, 1999;Coughlin et al, 2000); however, the strength of the association remains uncertain because of the retrospective design of most analyses and the reliance on nextof-kin respondents. Prospective studies can overcome these limitations. We examined the relation between cholecystectomy or gallstones and pancreatic cancer risk in two large cohorts, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). MATERIALS AND METHODS Study cohortsThe Nurses' Health Study (NHS) enrolled 121 700 female, registered nurses aged 30 -55 years in 1976, and information on their health status, medical history, and known and suspected risk factors for cancer and coronary heart disease was gathered through mailed questionnaires. The Health Professionals Follow-up Study (HPFS) began in 1986, when 51 529 American male dentists, o...

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Section: Discussionmentioning

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Gallstones, cholecystectomy, and the risk for developing pancreatic cancer

et al. 2002

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“…Of the five available studies assessing bile duct cancer risk specifically (Chow et al, 1994(Chow et al, , 1999Samanic et al, 2004;Oh et al, 2005), one reported an increased risk in white men but not white women, two small studies reported no association between obesity and ampullary cancer (Chow et al, 1999), whereas one large study showed elevated risk of ampullary cancer in US black men (Samanic et al, 2004). In two studies, tumours of the extrahepatic bile duct and/or the ampulla of Vater were combined with gall bladder cancer and were not evaluated separately (Lew and Garfinkel, 1979;Engeland et al, 2005).…”

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confidence: 99%

Body size and the risk of biliary tract cancer: a population-based study in China

et al. 2008

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Though obesity is an established risk factor for gall bladder cancer, its role in cancers of the extrahepatic bile ducts and ampulla of Vater is less clear, as also is the role of abdominal obesity. In a population-based case -control study of biliary tract cancer in Shanghai, China, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for biliary tract cancer in relation to anthropometric measures, including body mass index (BMI) at various ages and waist-to-hip ratio (WHR), adjusting for age, sex, and education. The study included 627 patients with biliary tract cancer (368 gall bladder, 191 bile duct, 68 ampulla of Vater) and 959 healthy subjects randomly selected from the population. A higher BMI at all ages, including early adulthood (ages 20 -29 years), and a greater WHR were associated with an increased risk of gall bladder cancer. A high usual adult BMI (X25.0) was associated with a 1.6-fold risk of gall bladder cancer (95% CI 1.2 -2.1, P for trend o0.001). Among subjects without gallstones, BMI was also positively associated with gall bladder cancer risk. Regardless of BMI levels, increasing WHR was associated with an excess risk of gall bladder cancer risk, with those having a high BMI (X25) and a high WHR (40.90) having the highest risk of gall bladder cancer (OR ¼ 12.6, 95% CI 4.8 -33.2), relative to those with a low BMI and WHR. We found no clear risk patterns for cancers of the bile duct and ampulla of Vater. These results suggest that both overall and abdominal obesity, including obesity in early adulthood, are associated with an increased risk of gall bladder cancer. The increasing prevalence of obesity and cholesterol stones in Shanghai seems at least partly responsible for the rising incidence of gall bladder cancer in Shanghai.

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“…However, over recent decades, the reported incidence has risen in China. 5 The etiology of gallbladder cancer is incompletely understood, like many other malignancies, this cancer is a disease of multifactorial etiology [6][7][8] ; gallstone are strongly associated with gallbladder cancer in both sexes and represent the most important risk factor for gallbladder cancer [9][10][11][12] ; other risk factors are some occupational exposures and chronic bacterial infections of gallbladder. [13][14][15] Although just how the biological mechanisms underlying them are involved in its development is not fully understood, one of the proposed mechanism involves oxidative DNA damage caused by reactive oxygen species (ROS).…”

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hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population

Jiao

Huang

et al. 2007

Intl Journal of Cancer

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The human oxoguanine glycosylase 1(hOGG1) gene encodes a DNA glycosylase that is involved in excision repair of 8-OH-dG (8-hydroxy-2-deoxyguanine) from oxidatively-damaged DNA. To determine whether hOGG1 plays a role in the risk for adenocarcinoma of the gallbladder, we tested the association of this polymorphism with gallbladder cancer in a Chinese population-based, case control study of 204 cases and 209 controls. The subjects were genotyped with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) assay. The association between the genetic polymorphism of this gene and risk of the cancer was examined by using a multivariate analysis. We found that the distribution of hOGG1 Ser326Cys genotypes among controls (Ser/Ser, 37.3%; Ser/Cys, 53.6% and Cys/Cys, 9.1%) was significantly different from that among gallbladder cancer cases (Ser/ Ser, 43.1%; Ser/Cys, 36.3% and Cys/Cys, 20.6%). Significantly increased risk for gallbladder cancer was both the hOGG1 326Ser/Cys (Odds ratio [OR] 5 1.9, 95% confidence interval (CI) 5 1.0-3.7) and hOGG1 326Cys/Cys genotypes (OR 5 4.5, 95% CI 5 1.1-22.4). We observed no statistically significant association between hOGG1 genotype and gallbladder cancer association in gallstone absence. In contrast, a near-significant increase in risk for gallbladder cancer was observed for gallstone presence with the hOGG1 326Ser/Cys genotype (OR 5 2.2, CI 5 1.4-3.5) whereas a significant increase in association for gallbladder cancer was observed for gallstone presence with the 326Cys/Cys genotype (OR 5 6.1, CI 5 2.1-27.2). These data corresponded with the fact that a significant trend towards increased association for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallstone presence(p < 0.001, v 2 trend test)but not in gallstone absence(p 5 0.89, v 2 trend test). A significant increase in risk for gallbladder cancer was observed for larger gallstone (those with stone diameters 2 cm or greater) with the hOGG1 326Ser/Cys(OR 5 1.9, 95% CI 5 1.1-2.9) and hOGG1 326Cys/ Cys genotypes(OR 5 5.9, 95% CI 5 1.6-18.0). These data are consistent with the observation that a significant trend towards increased risk for gallbladder cancer was observed with potentially higher-risk hOGG1 genotypes in gallbladder cancer patients with larger gallstone (p < 0.001, v 2 trend test). However, we observed no statistically significant association between hOGG1 genotype and gallbladder cancer risk in gallbladder cancer patients with smaller gallstone (those with stone diameters 2 cm smaller) (hOGG1 326Ser/Cys:OR 5 2.2, 95% CI 5 0.8-4.0; hOGG1 326Cys/Cys:OR 5 2.9, 95% CI 5 0.6-29.4; p 5 0.06, v 2 tread test). These results suggest that hOGG1 Ser326Cys polymorphism is associated with gallbladder cancer risk. ' 2007 Wiley-Liss, Inc.Key words: gallbladder cancer; hOGG1; polymorphism; susceptibility; China Carcinoma of the gallbladder has a very unusual geographical distribution with pockets of high incidence seen in Chile, Poland, India, Japan and Israel, 1-4 it occur...

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Gallstones, cholecystectomy and risk of cancers of the liver, biliary tract and pancreas

Cited by 133 publications

References 16 publications

Gallstones, cholecystectomy, and the risk for developing pancreatic cancer

Gallstones, cholecystectomy, and the risk for developing pancreatic cancer

Body size and the risk of biliary tract cancer: a population-based study in China

hOGG1 Ser326Cys polymorphism and susceptibility to gallbladder cancer in a Chinese population

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