Cancer Incidence in Thailand, 1988 19911

Vol. 4. 475-483, July/August 1995 Cancer Epidemiology, Biomarkers & Prevention 475

Cancer Incidence in Thailand, 1988_19911

V. Vatanasapt, N. Martin, H. Sriplung, K. Chindavijak, until 1986 that the first population-based cancer registry was S. Sontipong, S. Sriamporn, D. M. Parkin,2 and J. Ferlay founded at Chiang Mai, in the northern region (2). This was Faculty of Medicine. Khon Kaen University, Srinagarind Hospital, Khon Kaen followed in 1988 by the registry in Khon Kaen in the northeast 401)02. Thailand IV. V., S. Sr.]; Faculty of Medicine, Chiang Mai University, (3), and in 1990 in Songkhla in the south. In 1991, it was Maharaj Nakorn Hospital. Chiang Mai 50002, Thailand (N. M.J; Faculty of decided that these three registries would produce a combined Medicine, Prince of Songkla University. Hat-Yai, Songkhla 901 12, Thailand [H. S.]: National Cancer Institute, Rama VI Road. Bangkok 10400, Thailand analysis of their results, including estimates for the country as [K. C.. S. So.]: and International Agency for Research on Cancer, 150 coors a whole. Because there was no registry present in the densely Albert-Thomas. 69372 Lyon Cedex 08. France ID. M. P., J. F.] populated central region, a population-based cancer survey was planned and carried out in Bangkok in 1992, with the objective of collecting data on residents of the metropolitan area Abstract diagnosed with cancer between 1988 and 1990. Results from three cancer registries (Chiang Mai, Khon This study is a summary of the full report on the project Kaen, and Songkhla) in different regions of Thailand and (4), which presents an overview of the cancer profile in the from a cancer survey in the population of Bangkok country as a whole, a comparison of regional differences, and during the years 1988-1991 are presented, together with a review of previous epidemiological studies. It thus provides a an estimate of the incidence of cancer for the country as guide to future priorities for research into cancer cause and a whole. Overall, liver cancer is the most frequent control. malignancy, but there are large regional differences in incidence and in histological type, with very high rates of cholangiocarcinoma in the northeast (associated with Materials and Methods endemic opisthorchiasis) but a more even distribution of Geography and Peoples hepatocellular carcinoma. Lung cancer is second in frequency, with the highest rates in northern Thailand, The Thai people almost certainly originated in southern where the incidence in women (Age Standardized Rate, China and migrated southwards to occupy what is now 37.4 per 100,000) is among the highest in the world. A modern Thailand, Laos, and eastern Myanmar up to the 13th link with tobacco smoking is suggested by similarly raised century AD. This population is culturally and religiously rates, especially in women, for cancers of the larynx and (almost entirely Buddhist) quite homogeneous, with regional pancreas. Cervical cancer is the most common differences but variations in the basic pattern. Subsequent malignancy in women, with relatively little regional migrations brought large numbers of Chinese. These were variation in risk, while the incidence of breast cancer is estimated to be 2.5 million in 1958, but migration virtually low. Other cancer sites showing moderately increased ceased in 1948; individuals of Chinese origin have taken rates include the lip and oral cavity, particularly in Thai names and are now assimilated to varying degrees, females from the north and northeast, where the chewing making up about 10-14% of the population. Most Thais of of betel nut remains common among older generations, Chinese origin live in central Thailand (especially Bangkok) nasopharyngeal cancer, carcinoma of the esophagus in or other urban centers. About 10% of the population is the southern region, and penile cancer, especially in the comprised of other ethnic groups, including some 500,000 north and northeast. Previous studies which have hill tribe peoples of northern Thailand, most originating in investigated the etiological factors underlying these southern China and migrating in the last 200 years, and the patterns are reviewed, and the implications for future peoples of the southernmost seven provinces, who are of research and for national cancer control policies are Malay origin and predominantly Muslim in religion. discussed. Thailand is divided into 72 provinces grouped within 4 geographical regions: the northern, northeastern, southern, and Introduction central regions (Fig. 1). The northern region is mountainous with relatively cool winter temperatures and is the home of In Thailand, as in several other countries in Asia, rapid socio- several minority tribes, some indigenous and others are more economic development and the control of noncommunicable recent migrants. The northeast is a semi-arid plateau which, disease have resulted in the emergence of cancer as the third most common cause of death after “heart disease” and accidents because it is the poorest part of the country, is attracting and poisoning (1). Although in the past some information on increasing industrial development. The population is culturally cancer patterns was available from hospital statistics, it was not similar to that of neighboring Laos and speaks a distinct lan- guage (Isan) related to modern Lao. The central region is one of the most fertile rice-growing areas on earth and contains the densely populated Bangkok Metropolis (population, 5.8 mil- Received I ))/ I 9/94: revised I /5/95; accepted I /6/95. lion). The south is physically quite heterogeneous, with its long I Financial support for this project was provided by the Cancer Research Foun- dation for the National Cancer Institute and the Oncological Society of Thailand. coastline and hilly interior given over to agriculture (fruit and 2 To whom requests for reprints should be addressed. rubber plantations), fishing, and tin mining.

issued by nonmedical personnel. Cancer is clearly underenu- merated, with many deaths recorded as “heart failure” or “old age.” However, it is unlikely that there are many “false-posi- tive” diagnoses; therefore, death certificates provide a useful check on probable cancer cases not identified during life. Bangkok. Bangkok has no population-based registry. A cancer survey was carried out during 1991 to identify all cancer cases in the residents of Bangkok diagnosed in the 3-year period 1988 to 1990. Data were collected from all government and major private hospitals (with more than 100 beds) in the city and adjacent provinces. The three university hospitals and few medical center hospitals already had well-established hospital cancer registries. In the other government hospitals, data on cancer cases were collected via medical record departments (including in- and out-patients) and from the pathology departments. For private hospitals, most cases were identified from in-patient records. All death certificates for Bangkok residents who died during 1988-1990 and which mentioned cancer as a cause were compared with the file of registered cases, and unmatched deaths due to “cancer” were included as “death certificate only” cases, with no trace-back to the original source. I

Population Denominators The person-years at risk were calculated for the relevant periods in each registration area, based upon annual projections by age group and sex (5). The average annual populations of the four areas were: 1.33 million for Chiang Mai, 1.74 million for Khon Kaen, 1.17 million for Songkhla, and 5.78 million for Bangkok. Data from the 1990 census (6) were used in the estimation of incidence in the national population. The regional populations are: northern, 10.6 million; northeastern, 19.0 million; southern, 7.0 million; and central, 17.9 million. Songkhla

Methods Average annual incidence rates, per 100,000, were calculated with age standardization performed by the direct method using the “world standard population.” ICD-O (7) was used by all

Fig. 1. Thailand: regions, and the areas covered by the cancer registries. centers to code cancer cases; this was converted to ICD-9 for reporting purposes. The data quality in the different centers was evaluated by comparing the percentage of cases with histological verification Sources of Cancer Data of diagnosis and the percentage registered from information on Chiang Mai. A population-based registry was founded in 1986 the death certificate only (8). in the University hospital. Data on cancer patients in this To estimate cancer incidence in the national population in hospital and in 6 private and 29 community hospitals in the 1990, the average annual age- (5-year age group) and sex- province of Chiang Mai (Fig. 1) are actively collected by the specific incidence rates in the four registries (Chiang Mai, registry staff. Cases for the period 1988-1991 are included. 1988-91; Khon Kaen, 1988-91; Songkhla, 1989-91; and Bangkok, 1988-90) were applied to the populations of the Khon Kaen. A population-based registration was started in respective regions in 1990. The sum of these provides the 1987, with data collection from the registry of the University estimated numbers of cancers by sex, site, and age group for the hospital, as well as from the regional hospital and other (27) country as a whole, and the corresponding incidence rates are public and private hospitals in the Khon Kaen province (Fig. 1). calculated using the 1990 census population. Cases for the period 1988-1991 are included. Songkhla. This registry began operation in 1990, receiving data from the two hospital registries in the University city (Hat Results Yai), as well as one other major hospital in the provincial There were an estimated 29,950 new cancer cases in men and capital (Songkhla). Cases for the period 1989-1991 are 29,517 in women in Thailand in 1990. Fig. 2 illustrates the included. percentage distribution of the 10 most common cancers in each All three cancer registries use death certificates as an sex. Tables 1 and 2 show, for males and females, respectively, additional source of information on cancer cases, although there the age-standardized incidence rates for the major cancers in is some variation in the procedures for the follow-up of death each of the four registry areas and the estimate for Thailand as certificate notifications. A certified cause of death is not very a whole. For comparison, age-standardized rates from the accurate in Thailand, with between 7 and 19% of certificates United States, Singapore, and Osaka (Japan) are also shown (8).

Males Females

Liver 26.8 Cen,is ______18.9

Lung 15.6 Liver 12.0

Stomach 3.6 Breast 11.1

Colon 3.5 Lung 8.8

Oral cavity 3.2 Ovary 3.7

Bladder 3.1 Oral Cavity 3.6

Skin’ 2.5 Thyroid 3.2

Oesophagus 2.5 Colon 2.9

Larynx 2.4 Leukaemia 2.7

Prostate 2.2 Skin’ 2.5

#{149}excluding melanoma

Fig. 2. The ten leading cancers in Thailand, 1990, as a percentage of the total, by sex.

The proportion of cases registered with histological con- cell carcinomas (38% in males and 25% in females; Table 5). firmation of diagnosis, or with no information other than that There was little geographical variation in this pattern. from the death certificate, is shown for the major cancer sites in Cervical Cancer and Breast Cancer. In women, the major Table 3. cancer is cervical cancer (18.9% of cancers in women), almost

Liver Cancer. The very high incidence of liver cancer in the twice as frequent overall as cancer of the breast (1 1 . 1 %). northeastern region (which contains about 34.9% of the na- Eighty-seven % of cervical cancer cases were squamous cell in tional population) results in this remaining the major cancer of type, with I 1% adenocancinomas; incidence rates were highest men in the whole country, with an estimated 8000 new cases in Chiang Mai and lowest in Songkhla in the south. Breast every year. Liver cancer is also the second most frequent cancer cancer incidence is low, particularly so in the more rural north- of women (12% of all cancers). Less than one-quarter of the east and south. Fig. 3 shows the age-specific rates for these two liver cancer cases registered had been biopsied, but there were cancers. Cervical cancer incidence rises to a maximum in age large regional differences in the histological type amongst those group 55-59 and then declines, while for breast cancer, mci- which had (Table 4). In Khon Kaen, 89% of liver cancers were dence rates increase until age 50-54, with almost no change cholangiocarcinomas, compared with only 2% in Songkhla in with age thereafter. the south, where hepatocellular carcinoma predominates (96% of cases), as it does in Bangkok (71%). Although biopsy rates Other cancer sites showing moderately increased rates may not be identical for the different types of liver cancer, it is include the lip (in Khon Kaen) and oral cavity, particularly in unlikely that cholangiocarcinomas are overrepresented in bi- females, nasopharyngeal cancer, carcinoma of the esophagus in opsy series, since diagnosis is relatively straightforward using Songkhla, and cancer of the penis. Incidence rates for other ultrasound and needle biopsy is relatively hazardous. cancers of the gastrointestinal tract (stomach, colon, rectum, Lung Cancer. Lung cancer is second in importance in males and pancreas) are low, as are those for the kidney, bladder, and (15.6% ofcancers) and fourth in women (8.8%). The incidence, prostate. in both sexes, is much higher in the north (Chiang Mai) than Skin Cancer. Despite the fact that all ofthe registries recorded elsewhere in Thailand, and the incidence in females (ASR,3 all diagnosed cases of skin cancer, the incidence rates are low. 37.4/100,000) is very high, considerably above that in the Of all skin cancer cases, 10.8% were melanomas, one-half of United States, for example (Table 2). Fifty-one % of the lung which were located on the lower limbs and one-quarter on the cancers registered with a specified histology are adenocarcino- trunk. The distribution of nonmelanoma skin cancers by sex, mas (45% in males and 63% in females), with 33.7% squamous histological type, and site is shown in Table 6. In men, squamous cell carcinomas are more common than basal cell; the reverse is true in women. In men, squamous cell carcinomas

3 The abbreviations used are: ASR, Age Standardized Rate; OR, odds ratio; OV, occur mainly on the lower limbs, while in women, the face is Opisthorchis vicerrini. the most common site. Basal cell cancers are located mainly on

Ta ble I Age-standa rdized inciden cc rates (world standard) in Th ailand and corn parison regist ries (male)

Singapore US” (SEER) Th51 I an d Japan” 1983-1987 1983-1987 Site (Osaka) National Bangkok Chiang Mai Khon Kaen Songkhla 1983-1987 Chin’se Mala White Black estimate 1990 1988-1991) 1988-1991 1988-1991 1989-1991 y

Lip ( I 4))) )).2 0. 1 0.4 0.3 0.2 0. 1 0. 1 0.3 2.3 0.1 Oral cavity (141-145) 5.1) 4.3 6.9 3.3 8.2 3.4 4.4 2.4 7.2 9.1 Nasopharynx (147) 3.3 3.6 3.6 3.5 2.4 0.6 18.1 4.3 0.5 0.8 Other pharynx (146. 148-149) 3.7 2.7 6.8 1.1 7.5 1.5 2.5 0.8 3.6 7.9 Esophagus (150) 4.1 4.3 3.9 1.7 9.7 8.4 10.9 1.2 4.1) 13.9 Stomach (151) 5.8 4.2 10.7 5.2 3.2 73.6 34.7 6.4 8.0 12.4 Colon (153) 5.5 5.8 5.6 5.4 5.1 14.8 2t).2 6.9 31.1 28.5 Rectum (154) 3.4 3.6 4.2 2.8 3.0 11.6 15.2 8.3 15.4 10.1 Liver (155) 40.5 9.7 27.9 94.8 10.7 41.5 26.8 13.2 2.4 4.2 Gallbladder. etc. (156) 2.2 1.1) 5.1 2.4 0.4 6.0 1.8 1.4 1.6 1.1 Pancreas (157) 1.9 1.5 3.2 1.0 2.7 8.9 5.1 4.1 8.2 11.1 Larynx (161) 4.)) 3.6 8.0 1.5 4.5 4.1) 6.1 1.2 6.8 9.1 Lung (162) 25.)) 21.9 49.8 14.7 16.3 41.5 69.7 34.0 64.3 90.0 Melanoma of skin (172) )).5 0.2 1.2 0.4 0.6 0.2 0.4 0.5 lt).8 0.4 Other skin (173) 4.1 2.8 6.2 4.3 3.7 1.2 8.9 4.3 4.6’ 2.5’ Prostate (185) 3.8 2.8 6.5 2.7 4.5 6.6 7.6 9.0 61.8 82.0 Penis, etc. (187) 2.)) 1(1 3.2 1.8 3.2 t).5 0.7 0.2 0.8 0.7 Bladder (188) 4.9 5.3 8.1 3.4 3.0 8.2 7.4 6.2 23.9 10.5 Thyroid (193) 1.2 0.8 1.6 1.3 1.6 1.1 2.0 2.8 2.2 1.0 Non-Hodgkin lymphoma 2.8 2.3 4.7 2.5 1.5 6.1 6.0 5.5 13.6 7.4 (200, 202) Hodgkin’s disease (201) 0.7 0.3 1.4 0.8 0.5 0.5 0.6 1.2 3.4 2.0 Leukemia (21)4-21)8) 3.7 2.6 5.1 4.7 3.4 5.8 5.5 5.2 10.4 7.6 All sites, excluding other skin 149.6 94.7 202.1 192.7 107.2 265.4 266.2 131.9 325.8 348.8 (140-208 excluding 173)

.‘ Source, Ref. 8. / US. United States; SEER, Surveillance. Epidemiology, and End Results Program.

‘ Excludes squamous and basal cell carcinomas.

the face (63% in men, 82% in women), with 9.4% of cases on tance. This probable underregistration should be taken into the trunk in men. account in interpreting the data in Tables 1 and 2. To a lesser Thyroid Cancer. Thyroid cancer is three times more frequent extent, the same questions concerning completeness can be in females than in males. In women, the highest incidence is raised in relation to Songkhla, since some of the data in the observed in Khon Kaen, where the majority of tumors were period analyzed were collected retrospectively; incidence rates follicular cell in type. The ratio of follicular to papillary carci- for same sites appear rather low, and the percentage of cases nomas was 1.4, compared to an average of 0.46 elsewhere. diagnosed histologically is relatively high. In consequence, it is likely that the data for incidence in Thailand are an underestimate of the true situation. The mci- Discussion dence rates for cancer at all sites (excluding skin; 149.6/ There is quite a large difference in the incidence rates for cancer 100,000 for men and 125.2/100,000 for women) are about as a whole in the different registries. In particular, the overall one-half those observed in Western countries but not very incidence in Bangkok is low (ASR: 97.4 and 87.5 in men and different from those elsewhere in the region. The estimated women, respectively) compared with Chiang Mai (ASRs, 208.3 all-sites, age-standardized incidence rates (excluding other skin and 189.6) and Khon Kaen (ASRs, 196.9 and 154.4). In part, cancer) for southeastern Asia in 1985 are 122.1/100,000 in men this reflects the quite different risks of different cancers with, and 137.7/100,000 in women (9). for example, very high rates of liver cancer in Khon Kaen. The accuracy of the national estimates also depends upon However, there is almost certainly a degree of underenumera- how representative of their respective regions are the incidence tion in Bangkok, where the data were derived from a one-time retrospective survey in over 40 hospitals rather than from an patterns in the four registration areas. There are few data available with which to check this; however, the regional pat- established concurrent cancer registration. Thus, for some cancers where one might have anticipated rather little regional terns from the national hospital registration scheme (10), which variation in incidence (leukemia, brain and nervous system, was estimated to cover 38% of hospital admissions in 1982, are melanoma, nonmelanoma skin cancer, and pancreas), the mci- broadly similar, although there are some exceptions. For ex- dence rates are almost always lower in Bangkok than in the ample, lung cancer comprised only 9.2% of female hospital provincial registries. Similarly, the percentage of cases regis- registrations in the northern region, compared to 18.6% of tered with histological verification is higher in Bangkok, for registrations in the Chiang Mai province (10). most cancer sites, than in Chiang Mai and Khon Kaen (Table Cancer of the Oral Cavity. Cancer of the oral cavity is 3). Although this may be the result of better diagnostic facilities common in Thailand with similar rates in the two sexes (in in the capital, it seems equally likely to be the consequence of other parts of the world, males outnumber females by between failure to identify cases diagnosed without laboratory assis- two and ten to one). In the north (Chiang Mai) and northeast

Tab le 2 Age-standardiz ed (world sta ndard) incidence rates in Thail and and comp arison registrie a (female)

Singapore” US” (SEER) Thaian 1 d Japan” 1983-1987 1983-1987 Site (Osaka) National estimate Bangkok Chiang Mai Khon Kaen Songkhla 1983-1987 Chinese Mala White Black 1990 1988-1990 1988-1991 1988-1991 1989-1991 y

Lip (141)) 1.4 0.5 0.4 3.5 0.8 0.1 0.2 0.1 Oral cavity (141-145) 3.4 2.6 4.9 3.8 3.7 1.4 1.6 2.9 3.7 3.0 Nasopharynx (147) 1.7 1.8 2.1 1.7 0.9 0.2 7.4 1.5 0.2 0.3 Other pharynx (146, 148-149) 1.0 0.5 2.4 0.6 1.3 0.3 0.3 0.4 1.3 1.7 Esophagus (150) 1.4 1.0 2.0 0.8 3.1 1.8 2.7 0.9 1.3 3.6 Stomach (151) 2.9 2.2 6.1 2.3 1.0 32.7 15.6 5.4 3.5 5.6 Colon (153) 3.7 3.5 4.6 3.9 2.8 10.1 18.1 5.5 23.6 24.2 Rectum (154) 2.2 2.2 3.5 1.6 1.7 6.3 10.5 6.6 9.6 8.1 Liver (155) 16.3 2.7 12.2 39.4 1.9 9.7 7.0 6.3 1.1 1.4 Gallbladder. etc. (156) 1.9 0.7 4.0 2.3 0.7 5.8 1.8 0.9 1.7 1.3 Pancreas (157) 1.3 0.8 3.2 0.6 1.2 5.0 3.4 2.0 6.0 8.6 Larynx (161) 0.7 0.3 2.7 0.1 0.3 0.3 0.7 0.8 1.4 2.0 Lung (162) 12.1 6.1 37.4 4.4 4.3 11.7 21.9 12.1 29.9 28.1 Melanoma of skin (172) 0.4 0.1 0.5 0.7 0.3 0.2 0.3 0.5 8.8 0.6 Other skin (173) 3.3 2.0 4.1 4.4 3.2 0.9 7.4 2.8 0.6’ 0.6” Breast (174) 13.5 15.9 16.9 9.7 12.1 21.9 31.6 23.2 89.2 65.0 Cervix uteri (1St)) 23.4 20.9 29.7 23.9 18.5 13.2 17.5 8.8 7.3 11.7 Corpus uteri (182) 2.9 2.8 4.2 2.5 2.2 2.7 6.4 4.2 19.2 9.7 Ovary, etc. (183) 4.5 3.4 4.8 6.2 3.2 5.5 8.6 9.6 12.5 7.4 Bladder (188) 1.4 1.2 3.2 0.7 0.5 2.0 2.4 1.3 5.9 3.8 Thyroid (193) 3.6 2.3 3.1 5.4 3.6 3.3 5.9 4.8 5.8 2.7 Non-Hodgkin lymphoma 2.1 1.6 2.5 2.9 0.7 3.4 3.9 4.7 8.9 5.0 (2(X), 202) Hodgkin’s disease (201) 0.3 0.3 0.5 0.4 0.2 0.2 0.3 0.4 2.5 1.1) Leukemia (2()4-208) 3.2 2.5 4.7 3.4 3.2 3.8 3.6 3.6 6.4 4.9 All sites, excluding other skin 125.2 85.4 185.5 150.0 78.4 155.2 185.6 1 18.0 276.3 226.5 (140-208 excluding 173)

“ Source. Ref. 8.

I, US, United States; SEER, Surveillance, Epidemiology, and End Results Program.

‘. Excludes squamous and basal cell carcinomas.

Table 3 Quality indicators: percentage of cases histologically verified, and Nasopharyngeal Cancer. The incidence of nasopharyngeal registered from death certificate only, by registry and major cancer site cancer is intermediate between the very high rates observed in southern China and those of European populations. There is a Bangkok Chiang Mai Khon Kaen Songkhla strong genetic component to the risk of nasopharyngeal cancer HV” DCO HV DCO HV DCO HV DCO (14), so that areas in which a significant proportion of the

Oral cavity (140-145) 87 3 90 1 82 3 84 3 population has some Chinese ancestry, such as Thailand, might

Esophagus (150) 68 12 59 - 48 8 69 7 be expected to show an increase in risk (15). Consumption of Stomach (151) 66 13 73 6 57 14 72 14 salted fish is a well-known risk factor in Chinese populations Colon (153) 63 12 67 2 47 21 72 6 (16). A case-control study by Sriamporn et a!. (17) found that Liver(l55) 48 23 39 6 11 19 39 14 the consumption of sea-salted fish was a risk factor (OR, 2.5) Larynx (161) 79 5 84 - 70 7 75 5 in the population of northeast Thailand, as were agricultural Lung (162) 63 15 59 4 46 19 67 10 occupations and wood-cutting (OR, 8.0). Skin (172-173) 97 1 97 1 87 1 94 3 Breast (174) 85 3 89 2 76 3 79 10 Esophageal Cancer. The incidence of esophageal cancer is Cervix (180) 91 1 96 0 70 9 85 3 rather low in Thailand, except for Songkhla in the south, where

All sites 76 10 67 9 43 18 74 10 rates in both sexes are moderately high (similar to Singapore Chinese). Chongsuvivatwong (18) found that tobacco smoking “ HV, histologically verified; DCO, death certificate only; -, zero; 0, <0.5. alone was not associated with a significantly elevated risk, but the risk for nonsmoking alcohol drinkers was 4.7 (nonsignificant because of small numbers). Subjects who both smoked and (Khon Kaen), betel quid chewing remains relatively common among female villagers, although the habit has declined in consumed alcohol were at a significantly higher risk (5.7) than recent decades (1 1). Local studies have shown this to be a abstainens. Rubber-processing, an important local industry, did significant risk factor in both sexes (12, 13). The reason why lip not confer an increased risk. In another case-control study (19), cancer comprises such a high proportion of oral cancers in past consumption of two species of bean, Archidendron jiringa females in Khon Kaen (the incidence rate is the highest re- (“Luk Nieng”) and Parkia timoriana (“Luk Rieng”), was found corded in the world), but is relatively rare elsewhere, is not to increase risk; in contrast, consumption of raw beans of clear. In men, the highest incidence is observed in Songkhla, Parkia speciosa (“Sataw”) was found to be protective. which has also the highest rates for cancers of the pharynx and Gastrointestinal Cancers. The incidence of other gastrointes- esophagus (see below); these cancers share common risk tinal cancers, stomach and colorectal, is low in the Thai pop- factors (tobacco and alcohol) with oral cancer. ulation. They have not been the subject of any epidemiological

Table 4 Distribution by cent ci and histological type : liver cancer. Number of cases and percentage o f known histological type

Bangkok Chiang Mai Khon Kaen Songkhla Total

No. % No. % No. % No. % No. %

Hepatocellular carcinoma 259 70.8 135 47.9 23 7.6 47 95.9 464 46.5 (8170)

Cholangiocarcinoma 86 23.5 128 45.4 268 89.0 1 2.0 483 48.4 (8140, 8141, 8160, 8161, and 8501))

Other 21 5.7 19 6.7 10 3.3 1 2.0 51 5.1

Not specified 362 480 2390 84 3316 (8000, 8()O1, 8002, 801)3, 8004, and 9991))

Total 728 762 2691 133 4314

Table 5 Distribution by histological type and sex: lung cancer cancers in the United States (22). High rates in Thailand have been convincingly linked to infestation with the liver fluke OV Male Female (23). The local habit of eating uncooked cypninoid fishes that No. % %“ No. % %“ are infected with OV is the source of the high prevalence in northeastern Thailand (24, 25); this dietary custom is some- Squamous cell carcinoma 453 19.4 38.1 147 11.9 24.7 (8070-8076) times practiced in the north but not at all in the south. The regional incidence of cholangiocarcinoma correlates well with Small cell carcinoma 1 18 5.0 9.9 37 3.0 6.2 the prevalence of OV infection (26), and there is a similar (8041-8043) association at the local (district) level in the northeast (27). In Adenocarcinoma 535 22.9 45.0 372 30.1 62.6 a recent case-control study in subjects from northeastern Thai- (8250-8251, 8140-8231, 8260-8550, land, OV infection, as measured by an elevated titer of anti-OV and 8571)-857l) antibodies, was strongly associated (OR, 5.0) with cholangio- Adenosquamous carcinoma 5 0.2 0.4 6 0.5 1.0 carcinoma (28), and the percentage of cases attributable to (8560) opisthorchiasis was 72% in males and 62% in females. Various Other 7 3.3 6.6 32 2.6 5.4 mechanisms have been proposed for the carcinogenic action of

Not specified 1 152 49.2 641 51.9 liver fluke infestation, including increased cellular proliferation (8(XX)-801 I, 8020-8022, and 9991)) in response to tissue damage, induction of nitric oxide syn- thetase by inflammatory cells, and increased activity of certain Total 2341 1235 carcinogen-metabolizing cytochromes of the P450 group (23). Percentage of those among the known histological cases only. Regular users of betel-nut (predominantly females) also had a high risk of cholangiocarcinoma (OR, 6.4; Ref. 28). The incidence of hepatocellular carcinoma in Thailand is too -- probably rather uniform between regions (29). A case-control 0 Cervix study in residents in northeastern Thailand (30) has confirmed 80 ‘ BreJ that chronic carriers of the hepatitis B surface antigen have a high relative risk (OR, 15.2). Hepatitis C infection appears to be rare (31). ! 60 - 7 In an early study, Shank ci’ a!. (32) found that estimated mortality rates from liver cancer in two areas were apparently related to exposure to aflatoxin-contaminated foodstuffs. How- ever, although aflatoxin has been detected in a variety of market I #{176} 20 foods in Thailand (33-35), direct measurement of aflatoxin- albumin adducts in sera from human subjects suggests that intake is relatively low (36). This is consistent with the low 0 t5225- 3 35. 4-66 70.75+ prevalence of G to T mutations at codon 249 of the p53 gene in sera and liver tissues from Thai patients with hepatocellular carcinoma (37). Fig. 3. Age-specific incidence rates per 100,000: cancers of the cervix uteri, and Pancreatic Cancer. The incidence of pancreatic cancer in breast. Thailand is low, but there is a 3- to 5-fold variation in incidence by geographical region, with the highest rates noted in Chiang Mai. This may relate to the greater prevalence of smoking in the studies. Rates of colon cancer have increased in Chiang Mai in north; certainly, the incidence of both larynx cancer and lung the last decade (20), possibly related to increasing consumption cancer is also high in Chiang Mai, and the sex ratios (M:F) for of meat and animal fat and decreasing consumption of vegeta- all three cancers are strikingly low [1.0 (pancreas), 3.0 (larynx), bles in the Thai population over the last 20 years (21). and 1.3 (lung)] in comparison to the other centers and the Liver Cancer. The incidence of liver cancer in Thailand is comparison populations in Tables 2 and 3. very high, and most of the marked regional variation is due to The high incidence of lung cancer in women in northern the very different risk of cholangiocarcinoma. This is normally Thailand recalls the high rates found in Chinese females, in a rather rare tumor comprising, for example, only 15% of liver whom a high proportion of tumors are adenocarcinomas which,

Table 6 Distribution by histological type and ho dy site: non-melanoma skin cancer

Sq uamous cell carcinoma (8050-8082) Basal cell carcinoma (8090-81 10) Other and unspecified

No. % No. % No. %

Male 173.0-173.3 Face 45 23.9 80 63.0 10 26.3 173.4 Scalp and neck 15 8.0 12 9.4 5 13.2 173.5 Trunk 23 12.2 12 9.4 5 13.2 173.6 Upper limb 11 5.9 5 3.9 5 13.2 173.7 Lower limb 65 34.6 2 1.6 7 18.4 173.8. 173.9 Other and unspecified 29 15.4 16 12.6 6 15.7 Total 188 127 38

Female 173.0-173.3 Face 43 38.4 142 82.1 15 37.5 173.4 Scalp and neck 7 6.3 7 4.0 7 17.5 173.5 Trunk 9 8.0 5 2.9 2 5.0 173.6 Upper limb 8 7.1 3 1.7 0 0 173.7 Lower limb 32 28.6 0 0.0 5 12.5 173.8. 173.9 Other and unspecified 13 11.6 16 9.2 11 27.5 Total 112 173 40

although associated with tobacco smoking, generally have no studies of breast cancer epidemiology in Thailand. The lower relative risks than squamous and small cell cancers (38, low risk may be a consequence of previously high levels of 39). In a case-control study in Chiang Mai (12), smoking of fertility (early age at first pregnancy and multiple births) and cigarettes and “Khiyo” (long, indigenous cigars) was associated low caloric intake (late menarche and low body mass). with nonsignificant elevated risks in both sexes, while chewing However, patterns of fertility and nutrition are changing fast of miang (fermented wild tea leaves) was associated with an in Thailand and have affected the regions of Thailand to increased risk of lung cancer in women (OR, 2.2). There has different degrees, as shown by the child (0-4) per 1000 been a rapid increase in tobacco consumption in Thailand since women (15-49) ratio. This ratio is lowest in Bangkok the 1960s (40), so that incidence rates of tobacco-related (187.6), followed by Chiang Mai (386.0), Khon Kaen cancers are likely to increase in future. (476.8), and Songkhla (599.9), a ranking paralleling the in- Melanoma. In common with other low-risk populations, mel- cidence of breast cancer (except for Bangkok, where the low anoma in Thailand affects primarily the lower limb and partic- ratio is a result of many young female immigrants, and the ularly the sole of the foot, a distribution noted in an earlier incidence of breast cancer is an underestimate). series of cases from Chiang Mai (41). This is very different Cervical Cancer. The high incidence of cervical cancer in from the pattern in populations of European origin in whom Thailand (estimated national age-standardized incidence is melanoma affects primarily the trunk (of men) and lower limb 23.4/100,000) is quite typical of other developing countries (of women), and risk is enhanced by preexisting nevi and in southern and southeastern Asia. In a case-control study in exposure to sunlight (42). Bangkok, Wangsuphachart et al. (44) found trends of increas- Nonmelanoma Skin Cancers. Nonmelanoma skin cancers are ing risk with young age at first intercourse and number of probably incompletely registered, since they may be treated in sexual partners, although these were not statistically significant. small hospitals or as out-patients and thus escape case-finding However, very few women reported having more than one procedures. However, underregistration is probably less sexual partner (only 8% of controls). High parity has also been marked than in Europe, North America, and Australia, where found to be an independent risk factor for cervical cancer in incidence rates are very much higher. The low incidence in some high-fertility populations (45); this would be important in Thailand is typical of other Asian populations living in equally Thailand, where past fertility of older women is high, particu- sun-exposed latitudes. The site distribution shows a predomi- larly in the more economically deprived areas such as the nance of head and neck and basal cell cancers in women, while northeast. In the Bangkok study (44), women with high parity in men, squamous cell tumors are more common, particularly were at higher risk than nulliparous women, but there was no on the lower limbs. This pattern was observed in an early study significant trend with increasing number of children. in Chiang Mai (41). It is very different from that in populations In other parts of the world where cervical cancer is fre- of European origin in whom basal cell carcinomas are much quent and where men have many sexual partners but women do more frequent than squamous cell carcinomas, which are lo- not, as in Latin America (46), the effect of the sexual behavior cated mainly on the head and neck (60-80%), with the upper of partners in disease risk has been demonstrated. This may be limb as the next most common site (10-20%) (43). Squamous particularly relevant in Thailand. cell carcinomas of the lower limbs are rare in European pop- Penile Cancer. A high frequency of penile cancer was noted in ulations; their frequency in Thailand may be related to trau- an earlier series based on histopathology data in Bangkok matic lesions of the leg and foot, but there are no relevant (1951-1956; Ref. 47), 6.3% of cancers in men, and in Chiang studies. Mai (1966-1975; Ref. 48), 6.5% of cancers in men. Frequen- Breast Cancer. Thailand has a low incidence of breast cancer, cies in the population-based data reported here are lower (2.9% with an age-specific pattern typical of developing countries in Songkhla and 1.6% in Chiang Mai), and this may correspond (Fig. 3): an increase in risk up to about age 50 and then a to a true decline in incidence. A similar dramatic decline in flattening off or an actual decrease in risk. There have been frequency has been reported for another population with pre-

viously reported high frequencies, in Hanoi, Vietnam (49). 7. International Classification of Diseases for Oncology (ICD-O). Geneva, Circumcision, especially in infancy, is protective against penile Switzerland: WHO, 1976. cancer (50), and Menakanit and Vanittarrakorn (48) noted that 8. Parkin, D. M., Muir, C. S., Whelan, S. L., Gao, Y-T., Ferlay, J., and Powell, J. (eds.) Cancer Incidence in Five Continents, Volume VI (IARC Scientific 23.4% of the cases in their series in Chiang Mai had phimosis. Publications No. 120). Lyon, France: IARC, 1992. Bladder Cancer. The incidence of bladder cancer in Thailand 9. Parkin, D. M., Pisani, P., and Ferlay J. Estimates of the worldwide incidence is low (as it is in other Asian populations), although there is of eighteen major cancers in 1985. Int. J. Cancer, 54: 594-606, 1993. considerable regional variation in incidence. The highest rates 10. National Cancer Institute. Cancer Statistics, 1982. Bangkok, Thailand: are in Chiang Mai, possibly related to the prevalence of smok- Department of Medical Services, Ministry of Public Health. ing as well as to the presence of certain occupations using dyes 1 1. Tansurat, P. Cancer of the oral cavity and oesophagus in Thais and Chinese. in several local handicrafts industries. Acts Un. Int. Cancer, 17: 877-880, 1961. 12. Simarak, S., Dc Jong, U. W., Breslow, N., DahI, C. J., Ruckphaopunt, K., Thyroid Cancer. The incidence of thyroid cancer is highest in Scheelings, P., and MacLennan, R. Cancer of the oral cavity, pharynx/larynx and the northeast, although usually it tends to be more common in lung in north Thailand: case-control study and analysis of cigar smoke. Br. island areas or those near to the sea, where iodine intake is J. Cancer, 36: 130-140, 1977. expected to be high. Elsewhere in Asia (e.g., Singapore and the 13. Vatanasapt, V., Sriamporn, S., and MacLennan, R. Contrasts in risk factors Philippines), papillary carcinoma is two to four times more for cancers of the oral cavity and hypopharynx and larynx in Khon Kaen, Thailand. In: A. K. Varma (ed), Oral oncology, Vol. II. Proceedings of the frequent than the follicular type (51); this pattern is observed in Intemational Congress on Oral Cancer, pp. 39-42. New Delhi, India: Macmillan Bangkok, Songkhla, and Chiang Mai, but the opposite ratio is India Ltd., 1991. found in Khon Kaen. This finding may relate to the low iodine 14. Lu, S-J., Day, N. E., Degos, L., Lepage, V., Wang, P. C., Chan, S-H., Simons, intake in the northeast where, in a recent survey, 10 to 50% of M., McKnight, B., Easton, D., Zeng, Y., and dc-The, G. Linkage of a nasopha- children were found to have thyroid goiters. In contrast, Chiang ryngeal carcinoma susceptibility locus to the HLA region. 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V Vatanasapt, N Martin, H Sriplung, et al.

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